Dissertation abstracton medicine on the topic

BAISOV AUBEKIR ZAURBEKOVICH

OPTIMIZATION OF THE RANGE OF MEDICINES USED IN DEGENERATIVE PROCESSES OF THE MUSCLE-MOTOR APPARATUS IN PHARMACEUTICAL ORGANIZATIONS OF THE STAVROPOL REGION

dissertations

for the degree of Candidate of Pharmaceutical Sciences

1 2 YANB 2С|2

Pyatigorsk 2012

The work was carried out in the State budget educational institution higher vocational education"Pyatigorsk State Pharmaceutical Academy" of the Ministry of Health and social development Russian Federation

Scientific adviser:

Doctor of Pharmaceutical Sciences, Professor Andreeva Irina Nikolaevna

Official opponents: MD, professor

Tyurenkov Ivan Nikolaevich

Lead organization:

Candidate of Pharmaceutical Sciences, Associate Professor Kabakova Taisiya Ivanovna

SBEE HPE "Kazan State Medical University" of the Ministry of Health and Social Development of Russia

The defense will take place on January 20, 2012 at 9 am at a meeting of the Dissertation Council D 208.069.01 at the Pyatigorsk GFA of the Ministry of Health and Social Development of Russia (357532, Stavropol Territory, Pyatigorsk, Kalinina Ave., 11).

The dissertation can be found in the scientific library of the Pyatigorsk SFA of the Ministry of Health and Social Development of Russia (357532, Stavropol Territory, Pyatigorsk, Kalinina Ave., 11).

Scientific Secretary of the Dissertation Council

E.V. Kompantseva

GENERAL DESCRIPTION OF WORK

Relevance of the topic. Preservation of health, increase in life expectancy and creative activity of the population, cardinal improvement of the quality of medical care is one of the most important social, biomedical and economic tasks.

Currently, in many countries, the problem of rational use of drugs (MP) is being solved on the basis of the results of pharmacoeconomic studies, since the presence of economic and pharmacological advantages creates confidence that a more effective, safe and economical treatment regimen is used.

Moreover, in recent times in modern medicine there is a change of priorities, when the goal is not only to fight for the duration, but also for the quality of life. In this regard, more and more attention is paid to diseases of the musculoskeletal system and connective tissue, which often take a person out of active life for a long time.

The most common form of joint damage is osteoarthritis, which is one of the causes of disability, causes a deterioration in the quality of human life and significant financial costs for its treatment. According to the literature data, 10.0-12.0% of the surveyed population of the USA and Europe suffer from arthrosis, 10.0-20.0% of the total population the globe, women are ill 2 times more often than men. Separate cases of joint pathology occur already at the age of 16-25 years. With age, the frequency of the disease increases and at the age of over 60 reaches 97.0%. According to statistics, chronic diseases of the joints and spine lead to temporary or permanent disability for about 1/3 of the population of developed countries.

For a long time, medical treatment of osteoarthritis was limited to the use of painkillers and non-steroidal anti-inflammatory drugs. The use of drugs from other groups, affecting, among other things, the pathogenesis of the disease, remained limited due to the lack of convincing evidence of their effectiveness.

Currently, the main group of drugs that affect the metabolic processes in cartilage tissue are the so-called slow-acting symptomatic drugs that can also have a structure-modifying effect - chondroprotective drugs.

So far, marketing and pharmacoeconomic studies of the drug market for the treatment of diseases of the musculoskeletal system and connective tissue have not been conducted in the North Caucasus region, although the overall incidence of this group of diseases over the past 10 years in the Stavropol Territory has increased by more than 40.0%.

Summarizing the above, we can conclude that it is necessary to conduct more detailed studies related to the development of methodological approaches to rational use Drugs for the treatment of arthrosis, which is impossible without conducting marketing research of the regional pharmaceutical market of chondroprotective drugs on the example of the Stavropol Territory.

All of the above made it possible to formulate the purpose and objectives of our scientific research.

Purpose and objectives of research. The purpose of this study is to develop evidence-based recommendations for improving the provision of patients with pathology of the musculoskeletal system with chondroprotective drugs on the example of the Stavropol Territory.

To achieve this goal, it is necessary to solve the following tasks: to study foreign and domestic literature regarding the use of chondroprotectors in diseases of the musculoskeletal system; ^ to analyze the main medical, demographic and social indicators characterizing the prevalence of diseases of the musculoskeletal system in the Stavropol Territory, to identify regional features;

^ explore state of the art regional pharmaceutical market of chondroprotective drugs used in the treatment of pathology of the musculoskeletal system;

S to study the preferences of doctors and end users of chondroprotective drugs in the treatment of arthrosis and osteochondrosis;

S justify the economic advantage of using expensive, but highly effective drugs from the standpoint of evidence-based medicine;

V to develop, based on the results of ABC- and XYZ-analysis, evidence-based guidelines on the formation of the optimal range of chondroprotectors in pharmacy organizations and pharmaceutical wholesalers.

Methodological basis and objects of research. The principles of a systematic approach in the study of marketing and the pharmaceutical market, the works of domestic and foreign scientists in the field of modern marketing and management were used as a methodological basis for dissertation research.

The object of the study was the regional pharmaceutical market of the Stavropol Territory, and the subject of the study was the range of drugs and dietary supplements for food used to treat diseases of the musculoskeletal system and connective tissue in the Russian Federation and the Stavropol Territory.

The initial information was the statistical reporting data of the Information and Analytical Center of the Ministry of Health of the Stavropol Territory for 2005-2010, price lists of supplier companies and data from the INPRO-Pharmmarket information program, departmental materials on the regulation of production, quality control and circulation of medicines on the Russian market, and also questionnaires, questionnaires, expert sheets filled in by the population and specialists (doctors and pharmaceutical workers).

In the process of performing the dissertation research, methods of logical, systemic, documentary and regional analysis were used, as well as marketing and sociological (comparisons, groupings, content analysis, ranking, interactive survey, questioning, and others) methods.

dy. The results of the study were processed using computer programs Access and Excel.

Scientific novelty. A comprehensive analysis of the main medical and demographic indicators made it possible to assess the prevalence of diseases of the musculoskeletal system and connective tissue in the Stavropol Territory: the incidence is 1.5 times higher than in other subjects of the North Caucasus Federal District. With the use of sociological research methods, the stereotypes and preferences of doctors, pharmaceutical workers, as well as end users were established, and an assessment was made of the rationality of using chondroprotectors in the prevention and treatment of diseases of the musculoskeletal system. Based on the study of the dynamics and consumption, ABC, XYZ-analysis of sales volumes, the study of expert opinion, an assessment was made of the assortment and price availability of domestic and imported chondroprotectors in the pharmaceutical market of the Stavropol Territory. Taking into account the pharmacotherapeutic efficacy established on the basis of evidence-based medicine data, the prospect of consumption of chondroprotectors in the region, primarily combined chondroprotectors, is shown.

Using the solvency adequacy ratio of the population, the economic benefits of treatment with expensive modern chondroprotectors (Alflutop amp., Dona amp., Dona sachets, Chondrolon amp.), As well as complex drugs - Artra, KONDRONOVA, Teraflex, Teraflex Advance, are shown and a commercial perspective is shown for including them in range of pharmacies.

The practical significance of the work. The performed studies allow us to have an idea of ​​the range of chondroprotective drugs available on the market, the structure of their consumption, demand trends, the level of effectiveness from the standpoint of evidence-based medicine, and to form an optimal assortment portfolio of chondroprotectors for pharmacy organizations and pharmaceutical wholesalers. This will allow them to solve social and commercial problems at the same time.

Implementation of research results into practice. On the basis of the data obtained, materials were prepared and introduced into practical pharmacy to raise the awareness of pharmaceutical workers in the form of a monograph "Chondroprotector pharmacotherapy", which are used in the educational process of the Department of UEF of the Faculty of Postgraduate Education (act of implementation dated 10.05.2011), the Department of Pharmacology (act of implementation dated

01/20/2010) Pyatigorsk State Pharmaceutical Academy. Methodological recommendations "Methodology for the formation of an optimal assortment portfolio of chondroprotectors for wholesale pharmaceutical organizations" were introduced into the activities of wholesale pharmaceutical companies ZAO NIK Katren, Mikhailovsk, Stavropol Territory (act of implementation dated

08/10/2011), State Unitary Enterprise "Pharmacy" North Ossetia-Alania (act of implementation dated 10/10/2010). Approbation of the research results. The main fragments of the dissertation work were reported and discussed at the 64th interregional conference on pharmacy, pharmacology and personnel training "Development, research and marketing of new pharmaceutical products" (Pyatigorsk, 2009); interregional scientific conference "Actual problems of pharmaceutical science and practice" (Vladikavkaz, 2010); international scientific and practical conference "Young scientists in solving urgent problems

Science” (Vladikavkaz, 2011).

Connection of research tasks with the problematic plan of the pharmaceutical sciences. The dissertation work was carried out in accordance with the research plan of the Department of Management and Economics of Pharmacy, Faculty of Postgraduate Education, Pyatigorsk State Pharmaceutical Academy of the Ministry of Health and Social Development of the Russian Federation (state registration number 01.2.001455).

Basic provisions for defense. The dissertation substantiates and formulates the following provisions for defense:

the results of the analysis of the range of chondroprotective drugs presented on the pharmaceutical market of the Stavropol Territory;

the results of determining the preferences of doctors when prescribing chondro-protectors and the characteristics of end-user demand; ^ results of determining the market capacity of chondroprotectors and strategically important commercial groups of chondroprotective drugs; methodological recommendations for the formation of an optimal assortment portfolio of chondroprotectors for pharmacy organizations and pharmaceutical wholesale organizations in the short, medium and long term; ^ proposals for optimizing the consumption of chondroprotectors based on

evidence-based medicine data. The volume and structure of the dissertation. The dissertation work consists of an introduction, three interrelated chapters, general conclusions, a list of references, applications, and is presented on 148 pages of text. computer set, contains 28 tables, 19 figures, a list of references, including 129 sources, including 5 - foreign authors.

Analysis of the state of drug care for degenerative diseases of the musculoskeletal system in Russia and abroad

AT recent decades there has been a significant increase in the number of diseases of the musculoskeletal system (diseases of the joints and spine), which are ranked 4th in terms of prevalence in developed countries. Among them, pathology of a degenerative-dystrophic nature (osteoarthrosis, osteoporosis, osteochondrosis) predominates. These diseases lead to a significant deterioration in the quality of life of patients and are a serious socio-economic problem.

Scientists and doctors different countries study the mechanisms of development and course of joint diseases, offer new drugs to combat them, but a radical remedy that can prevent them has not yet been found.

In addition, diseases of the musculoskeletal system (MBMS) are among the most expensive worldwide. All three components total costs for a disease (diagnosis, treatment, rehabilitation) are characterized by high costs, comparable to those for cancer patients. The average cost of treating one patient with BCCM in developed European countries is more than 15 thousand rubles. euro per year. The principles of treatment of BCSM are based on a complex step-by-step therapy, the basis of which is anti-inflammatory therapy with non-steroidal anti-inflammatory drugs. However, in last years Increasing attention is paid to drugs that change the course of the disease, which contribute to the long-term maintenance of the functioning of the joints and spine - chondro-protectors. Over the period from 1980 to 2010, more than 40 clinical studies were conducted, which had a sufficient degree of reliability. Chondroitin sulfate and Glucosamine are the most studied. The growth of the nomenclature of drugs significantly increases the possibility of choosing drugs, taking into account solvency and individual features every patient. However, the rationality of drug prescribing, determined by the preferences and professional knowledge of medical workers, is influenced by regional conditions the functioning of healthcare.

Therefore, the issue of conducting marketing research on the market of chondroprotectors in the Stavropol Territory and developing methodological approaches to their rational use has become ripe.

Analysis of the consumption dynamics of chondroprotectors and their pharmacoepidemiological assessment

To carry out the research, an algorithm was developed based on the methodology of pharmacoepidemiological studies of the laboratory of pharmacoeconomics of the Research Institute of Pharmacy of the MMA named after I.I. Sechenov. The main stages included the study

the spread of the incidence of the musculoskeletal system in the region, the analysis of the range of chondroprotective drugs, the study of their regional market and the assessment of the possibility of implementing the requirements of modern approaches to treatment in conditions of limited financial opportunities patient.

In the course of the study, its phased implementation was carried out. As a result of the research, unfavorable trends in the medical and demographic situation of the region were revealed, which manifest themselves in the annual decline in the population by an average of 3.0% (as of 01.01.2011, 2707.3 thousand people); in the aging of the population (13.5% of the inhabitants of the Stavropol Territory are older than 65 years, and 24.0% are older than working age). Against the background of a general deterioration in health indicators, there is an increase in diseases of the musculoskeletal system (99.6 people per 100,000 population). For five years (2005-2010), the incidence of this nosology increased by 40.0%.

^The main pharmacological groups for drug therapy in the treatment of diseases of the joints and spine are non-steroidal anti-inflammatory medications and chondroprotectors. The comparative novelty of the use of the latter and the insufficient knowledge of the regional market became the basis for a detailed study of chondroprotectors.

The modern classification of chondroprotective drugs is under development; according to the ATC classification, they are classified as direct non-steroidal anti-inflammatory and antirheumatic drugs M01AX. The following pharmacological classification is most acceptable (Table 1).

We have analyzed the range of chondroprotectors in the pharmaceutical market of the Stavropol Territory according to four supplier companies that provide 70.0% of the market volume: CJSC SIA International, NIK KATREN, CV PROTEK, CJSC Apteka Holding using the software package "Improfarmrynok" for 2008-2010 It was established that out of 42 TN drugs of the group "Bone and cartilage tissue metabolism correctors" there are 36 TN drugs on the pharmaceutical market of the Stavropol Territory, of which 2 drugs are new as of 01.01.2011. (Unium, Chondro). Among

72.2% of drugs represented by LP are representatives of chondroitin and its combinations with other chondroprotectors, 11.0% are glucosamine preparations, the rest are hyaluronic acid preparations and polysaccharide-protein complexes.

Table 1 - Classification of chondroprotectors

Name of the group Relate to the generation according to the degree of knowledge Representatives

Acting mainly on cartilage 11th generation with proven efficacy (class 1A) Chondroitin sulfate and its various dosage forms: Structum cape., Chondrolon apm., Chondroxide tab.

Acting on the subchond-I generation with a low degree of evidence of the effect Alflutop, Rumalon, Arteparon, Mu-cartrin

Synthesis stimulators II generation with proven efficacy (class IA) Glucosamine sulfate and its preparations: Dona. Yunium, Diacetylrhein

Joint structure modifying drugs K generation with weak evidence base for effectiveness Hyaluronic acid and its dosage forms

Combined preparations of the 3rd generation with proven efficacy (class! A) Combination I of lucosamine and Chondroitin and NSAIDs: ARTRA, KONDRONOVA, Teraflex, Teraflex Advance

An analysis by production line showed that the share of domestic chondroprotectors is small and amounts to only 28.0%, the share of imported drugs, respectively, was 72.0%.

The geography of producing countries is very diverse - 13 foreign countries; the United States is in the lead - 21.0%, Switzerland - 9.1%, Germany and France 7.1% each, that is, mainly manufacturers of original drugs. The bulk of drugs are OTC drugs - 61.0%.

Systematization by release forms showed that the range of chondroprotectors contains oral, injectable and soft dosage forms. The share of solid dosage forms is 73.3%, injectable - 13.3%, soft - 13.4%.

The cost analysis made it possible to establish that the cost of chondroprotective drugs varies in the price range from 50 rubles. up to 1000 rubles and higher (table 2).

Table 2 - Price range of chondroprotective drugs

Drug tolerance

From 51 rub. up to 200shb

From 201 rub. up to 500 rubles

From 501 rub. up to 1000 rubles

From 1001 rub. and higher

Segment share, 5

An analysis of price segments showed that more than half of chondroprotective drugs have a high price - more than 500 rubles. - price. Whereas cheap drugs (from 50 rubles to 200 rubles) are few in number - 19.4%.

In this regard, the sales volumes of this group of drugs in the Stavropol Territory for the period 2008-2010 were analyzed. (picture 1). 122000

X 117000 g 116000 115000 114000

2009 2010

Figure 1 - Dynamics of sales of chondroprotectors in the Stavropol Territory for 2008-2010

It should be noted that for the period 2008-2010. there is a decrease in sales of drugs with chondroprotective activity. This, apparently, is due to market instability and the economic crisis, as well as an increase in prices for this group of drugs by an average of 10-12%.

An analysis of the sales leaders for this period showed that they did not change during the analyzed period of time, and for some positions it is noted

even sales growth (Table 3).

In the region, despite the price increase, sales volumes of original preparations of Chondroitin sulfate increased (Structum cape. +72.5%, Honda-rolon amp. +5.3%); Glucosamine sulfate (Don amp. + 2.0%, Don sachet + 4.0%). At the same time, sales of Piascle-

dina cape, based on avocado oil, and, as studies have shown, in 2010, sales of biologically active food supplements (Ino-ltra, Chondramin, Chondroitin healthy joints) stopped altogether. Also in the region sales of Hyaluronic acid tab. (Japan), Chondroitin-Akos ointment 5% (Russia), Glucosamine sulfate tab. (Russia). Sales of complex preparations ARTRA, KONDRONOV decreased. The market of the Stavropol Territory is characterized by low sales volumes of Teraflex and Teraflex Advance.

Table 3 - TOP-13 Sales leaders among chondroprotectors for 2008 - 2010

Name of the drug Number of pack. sold per year

29 633 29 759 29 895

Hondrolon amp. No. 10 23 490 23 725 24 739

22 269 22 376 19 132

Chondroitin-AKOS cape. 0.25g №50 8 119 8 155 8 053

6 942 6 996 7 210

Chnproitin-AKOS ointment 5% 30.0 4249 4271 4322

2 816 2 847 2 870

Donapore 1500mg sachet №20 2638 2686 2744

Struetum cape. 500mg #60 1639 1678 2828

2 287 2 328 2 414

4 044 4 086 2 052

1 639 1 700 1 718

Chondroxide tab 250mg №60 1512 1558 1638

Thus, the analysis of the pharmaceutical market showed the possibilities for organizing a rational therapy for diseases of the musculoskeletal system using drugs that can slow down degenerative processes in the joints. However, the lack of highly effective and new drugs in the leaders of sales required a study of the information needs and consumer preferences of both intermediate and end consumers.

The number of respondents was calculated based on the general population registered with BCM in the Stavropol Territory in 2010. The questionnaire included 10 questions characterizing the age and gender differences of patients, the proportion of workers, pensioners with disabilities, the awareness of patients about BCM, effectiveness treatment from the patient's point of view.

In the survey, the dominant age group was the

respondents over 60 years of age (68.0%), with 54.8% women and 45.2% men. It has been established that diseases of the musculoskeletal system affect all segments of the population, regardless of education and social status. Among the respondents, the majority had a disease duration exceeding 10 years (52.0%).

A survey of the target group of patients showed that 92.6% of patients at least occasionally took chondroprotective drugs. About 20.0% of patients discontinued their use after one course of treatment. Most common causes insufficient adherence to therapy was the high cost and duration of the drug use.

Evaluation of the effectiveness of treatment and compliance of patients was carried out to eliminate symptomatic syndromes - reducing pain and increasing joint mobility. Patients' self-assessment of the effectiveness of the treatment performed showed that 52.0% of patients consider treatment with chondroprotective drugs effective, 39.0% - ineffective, and 9.0% - doubt its expediency. That is, slightly less than half of patients require attention from doctors to determine the inadequacy of treatment.

An analysis of the financial capabilities of patients revealed the following: 37.5% of rural residents and 19.51% of urban residents consider chondroprotective drugs to be expensive and can afford to be treated only with drugs costing up to 500 rubles, as a rule, these are generic drugs, both imported and domestic. Medicines in the new range from 500 to 1000 rubles. acquired mostly by citizens; these are mainly original imported drugs (Table 4).

Table 4 - Analysis of the costs for the purchase of chondroprotectors by residents of the Stavropol Territory

Place of residence Amount of costs for the purchase of medicines

up to 500 rubles 501-1000 rub. 1001-1500 rub. more than 15 30 rub.

people 80% 19.51 people 186% 45.36 people 84% 20.48 people 60% 14.65

In rural areas Total population 154,234 37.5 28.53 173,359 42.19 43.78 62,146 15.17 17.8 21 81 5.14 9.89

The results obtained indicate that, despite the high cost of chondroprotective drugs, patients acquire them in most cases in the treatment of osteoarthritis and osteochondrosis and, mainly, at their own expense.

The next stage of the research was a survey of medical workers, of which 52.0% were general practitioners, 27.0% were rheumatologists and 21.0% were neuropathologists.

An analysis of therapeutic prescriptions among doctors of various specialties revealed their preferences for chondroprotectors (Table 5).

Table 5 - Analysis of therapeutic prescriptions among doctors of various specialties in relation to chondroprotectors

Name of the drug Frequency of prescriptions by doctors:

therapists rheumatologists neuropathologists

Alflutop amp. 3.4 22.4 45.2

Donamp. 4.6 44.6 20.4

Hondrolon amp. 10.2 45.4 19.6

Dona sachet No. 10 27.8 22.6 15.6

Structum cape. No. 60 42.4 25.6 24.3

Chondroxide tab № 100 45.6 10.4 5.6

Chondroxide gel 32.6 6.4 2.9

Chondroxide ointment 16.2 10.2 .3.5

Stopartrose sachet No. 20 7.2 7.6 4.2

KONDRONOVA amp. No. 60 5.3 18.4 12.6

ARTRA cape. No. 30 8.6 22.4 3.5

Teraflex tab. No. 60 2.6 4.5 2.3

As the data shown in Table 5 showed, doctors have different adherence to LP: rheumatologists prescribe injectable forms of Glucosamine sulfate and Chondroitin sulfate, as well as original drugs in the form of Dona and Structum capsules; general practitioners are more committed to oral basic drugs, both original and generics (Glucosamine and Chondroitin), neuropathologists often prescribe Alflutop in ampoules. Combined drugs of the third generation are prescribed by rheumatologists. Soft dosage forms Chondroxide gel 5.0% and Chondroxide ointment 5.0% are preferred by general practitioners.

Thus, the structure of demand for chondroprotective drugs in the Stavropol Territory, which is defined as adherence to

physicians and behavioral patterns of patients. Ampoule preparations are in the greatest demand in the region: Alflutop, Dona, Hondrolon; oral original drugs: Dona, Structurm, KONDRANOVA, ARTRA and soft drugs Chondroxide - ointment and gel.

Optimization of providing the regional market with chondroprotectors used in diseases of the musculoskeletal system

In order to improve the organization of drug care for patients with BCM, taking into account the economic, socio-demographic conditions prevailing in the Stavropol Territory, we carried out a cost estimate of drug care for patients. For this, the cost of a course of treatment of BCM with TOP-13 drugs by the leaders of sales with chondroprotective activity was calculated (table b).

The research results indicate that the treatment of BCSM with chondroprotective drugs is an expensive and time-consuming process. As a result of studying the comparative cost of a course of therapy with chondroprotective drugs, it was found that the cost of the course depends on the type dosage form. Treatment with ointments costs 400 rubles, ampoules 2000-2500 rubles, tablets and capsules from 2000 rubles. (KONDRANOVA amp.) up to 6432 rubles. (Don sachet). I would like to note that none of the chondroprotectors is included in the Vital and Essential Drugs and these drugs are not available in the purchases of medical organizations, that is, those suffering from BCM must purchase drugs that have chondroprotective activity at their own expense.

At the core modern treatment osteoarthritis lies pathogenetic approach. In the recommendations of the European Antirheumatic League (EuLAA), drugs for the treatment of patients Chondroitin sulfate and Glucosamine hydrochloride have a high level of evidence and recommendation value (1A). With regard to Alflutop and Chondroxide ointments, as well as domestic generics, the level of evidence from clinical trials is low (according to EuLA).

Table 6 - Comparative cost of the course of treatment of diseases of the musculoskeletal system with drugs TOP-13 sales leaders with chondroprotective activity

Name of the drug Release form Course of treatment Cost of a daily dose Cost of a course of treatment Class of evidence

Alflutop ampoules No. 10 20 days, repeat six months later 120.30 rubles. 2 406 rub 11

Chondrolon ampoules No. 10 30 injections; repeat after 6 months. RUB 80.80 2 424 rub. IA

Chondroitin-AKOS capsules 0.25g No. 50, 3 caps. 2 times a day for 6 months RUB 24.48 2 856 rub. And

Chondroxide gel 5% 30.0 tablets 250 mg No. 60 ointment 5% 50.0 21 days 3 tablets 2 times a day for 6 months. 14-21 days RUB 19.23 RUB 29.7 15 rub. 404 rub. 3 564 rub. 316 rub. W

Dona ampoules No. b with a pore solvent. 1500 mg sachet №20 1 time per day for 4-6 weeks 1 time per day for 4 months. RUB 130.50 RUB 35.33 2 349 rub. 6432 rub. IA 1A

Artra tablets No. 60 1 tab. 2 times a day for 6 months. RUB 37.25 4470 rub. 1A

Piascledin capsules 300mg No. 15 1 cape. 2 times a day for 6 months. 24 rub. 4 320 rub. 1A

Stoparthrosis sachets 1200 mg №20 1 powder per day for 3 months. 29 rub. 2 900 rub. -

Structum capsules 500mg №60 1 cap. 2 times a day for 6 months RUB 33.16 5 970 rub. IA

KONDRONova capsules 500 mg No. 60, 2 caps. 2 times a day for 2 months RUB 16.66 2 000 rub. 1A

Teraflex capsules № 100 2 caps. 3 times a day for 6 months. 66 rub. 4 400 rub. IA

Ca.5.= ^-^--100% ¡V

where Ca.e. - solvency adequacy ratio;

a - the number of packages of the drug of a certain dosage form required for treatment during the 1st month;

P - the average price of the drug for a certain period (month); \Va.w. - average salary for a certain period (month).

The introduction of an additional variable makes it possible to more objectively assess what part the treatment with a drug of a certain dosage form takes in the sum of the average monthly wages, while the availability factor, shows directly proportional dependence this coefficient from the cost of the drug.

Therefore, the calculation of Sa.B. for TOP-13 sales leaders among chondroprotectors for 2008-2010. When calculating, we used the amount of the average salary in the UK (according to the data of the Territorial body of the state statistics service for 2010) equal to 9410 rubles. The calculation data are presented in Table 7.

Table 7 - Solvency adequacy ratio for the TOP-13 sales leaders among chondroprotectors (for the period 2008 - 2010)

Name of the drug

Upflutop amp. No. 10

Hondrolon amp. No. 10

Chondroxide ointment 5% 50.0

Chondroitin-AKOS cape. 0.25g

Chondroxide gel 5% 30.0

Chondroxide tab. 250 mg No. 60

Dona amp. No. 6 with solution. ^1 she is now. 1500 mg sachet №20 Structum cape. 500mg #60

Artra tab. No. 60

KONDRON cape. No. 60

Teraflex cape. No. 100

Average retail

appreciating the drug

The duration of the course of treatment

6 months

6 months

6 months

Number of packs per course

6 months

6 months

Solvency adequacy ratio, %

Low solvency ratio for domestic drugs Chondroxide tab. 250 mg No. 60, Chondroxide ointment 5% 50.0 g and Honda-rolon amp. No. 10 indicates their affordability for low-income segments of the population. The ratio of the calculated coefficients made it possible to identify the economic advantage of treatment with injectable drugs compared to oral chondroprotectors by 2-2.5 times; combination drugs Artra tab. No. 60, Teraflex cape. No. 60 by 1.5 times in comparison with the monopreparations Don sachet No. 20 and Structum cape. 500 mg No. 60, and the Indian drug KONDRONova cape. No. 60 gives mainly 6 times.

The next stage of research was the identification of strategic groups of chondroprotectors using a combined technique of ABC and XYZ analyses. For this, an integrated ABC-XYZ-analysis matrix was compiled, from which it follows that chondroprotectors belong to the group of pharmacy products, the consumption forecast of which is difficult, since there are no high degree reliability of consumption indicators - only 4 drugs fell into the AX and VC groups: These are cheap complex drugs, such as: Chondroitin AKOS tab., Chondroitin ointment, gel, Chondroitin ointment, gel.

Table 8 - Matrix of ABC and XYZ analyzes of the range of chondroprotectors

Artra cape.

i Chondroitin AKOS Alflutop amp. Artra tab.

and tab. Dona amp. Chondroitin sulfate

■0 a Dona sachet liof.

Inoltra (dietary supplement)

X Hyaluronic Acid

* a Chondroxide ointment Chondrolon amp. tab.

es 3 h Chondroxide gel Stopartrosis sachet Artra chondroitin cape.

a. With.

in as ointment Piascledin cape. Structum cape.

3 CX SU C b

Chondroitin healthy

joints (BAA)

o¡ Chondroxide tab. Chondroitin Glucose-

ut Chondroitin gel Chondro new complex (BAA)

Chondroitin ointment Sustanorm Teraflex cape.

Yunium Chondramin (BAA)

Glucosamine sulfate

Chondroitin Verte Cape.

high medium low

Consumption stability

The VU group included expensive drugs (Chondrolon amp., Stopartroz sachets, Artra tab.), the AC group included drugs with a high share in sales, but average consumption stability due to high prices. The Cb group included drugs that are dietary supplements.

Drugs belonging to the category AX, AU, K1 can be characterized as highly profitable, stably sold. It is advisable for pharmaceutical organizations to purchase drugs of this group at their own expense on the terms of payment upon shipment or prepayment.

It is advisable for large pharmacies to purchase expensive drugs (Alflugop, Dona, Chondrolon, Stopartrosis) at their own expense or on the terms of a small deferred payment, depending on the marketing policy adopted by the organization. Small pharmacies - on the basis of guaranteed sales on order or a long-term deferred payment of 45 days or more.

assortment to pharmacies of all categories.

Acquisition of drugs of other categories: CX, SU, SG, is rational only for large and medium-sized pharmacies on the terms of a long-term payment delay

(more than 30 days).

It is rational to introduce combined chondroprotectors into the assortment, taking into account the basics of evidence-based medicine - CONDRONova cape, Artra cape., Teraflex cape., Teraflex-Advance cape.

Thus, the conducted studies have shown the need to take into account the assortment characteristics of chondroprotectors in order to determine the optimal assortment that allows for maximum economic efficiency and rational selection of drugs for their use.

applications in the treatment of BMS.

The results obtained formed the basis of guidelines for pharmacies and wholesale pharmaceutical organizations on improving the assortment policy for chondroprotective drugs, as well as in the educational process of the faculty of postgraduate education and students of the pharmaceutical academy.

GENERAL CONCLUSIONS

1. An analysis of foreign and domestic literature on the study of the market of drugs used in the treatment of joint pathology showed that in recent years the demand for chondroprotective drugs that can slow down or stop the progression of the disease has increased.

2. A scientifically substantiated methodological approach to the pharmacoepidemiological analysis of the treatment of diseases of the musculoskeletal system, based on the principles of marketing research on the market of chondroprotectors, factors affecting their demand, assortment and price availability, effectiveness from the standpoint of evidence-based medicine.

3. When analyzing the medical, social and demographic indicators of the Stavropol Territory, a trend towards an increase in the proportion of diseases of the musculoskeletal system was established: over 10 years, the growth was 40.0%, the incidence rate is 9.9 people. per 1000 people population, which is higher than the average for the North Caucasus region.

4. It was determined that the range of chondroprotective drugs in the pharmaceutical market of the Stavropol Territory is saturated: the market completeness coefficient is 0.85; depth factor 0.87, update index 0.1%.

5. It was revealed that chondroprotectors are drugs with high commercial potential, however, the economic crisis affected the level of sales of this group: sales decreased from 2008 to 2010 by 10.2%. Price segmentation of chondroprotectors showed that 73.4% of drugs cost more than 250 rubles.

6. The structure of consumer preferences for chondroprotectors has been established - 71.47% of respondents prefer imported expensive drugs, 28.53% 0 prefer cheap drugs of domestic production. The greatest demand among the population and frequently prescribed by doctors are injectable drugs: Alflutop amp., Chondrolon

amp., Dona amp.; LP for external use: Chondroxide ointment, Chondroxide gel; and oral original drugs: Structum capsules, Dona powder, the same drugs, received the highest rating from expert doctors in terms of competitiveness.

7. The economic advantage, calculated by the solvency adequacy ratio, belongs to the drugs Alflutop, Chondrolon, Dona amp., KONDRONova cape., Teraflex and Teraflex Advance, which are more effective from the standpoint of evidence-based medicine of the domestic analogue of Chondroxide tab.

8. According to the results of the study of assortment analysis using ABC - and XYZ - methods, the principle of including chondroprotectors in the assortment portfolio of wholesale pharmaceutical and pharmacy organizations was formed: in the short term, the group AX-AY: 10 drugs; in the medium and long term, one should rely on the level of evidence of a therapeutic effect, which is high in Don amp., Chondrolon amp. and combined preparations of the third generation: Artra cape., KONDRONova cape., Teraflex cape.

1. Baisov, A.Z. The state of the incidence of the musculoskeletal system in the population of the Stavropol Territory / A.Z. Baisov, S.A. Parfeinikov, T.M. Bondareva // Pharmacy and public health: materials annually. conf. 25 Feb. 2010 - Yekaterinburg: UGMA, 2010. - S. 322-324.

2. Baisov, A.Z. Marketing research of the regional market of medicines prescribed for the treatment of arthrosis / A.Z. Baisov, I.N. Andreeva, A.I. Bylim // Actual problems of pharmaceutical. science and practice: Sat. scientific tr. Vseros. scientific - pract. conf. October 28-30, 2009 - Vladikavkaz: SOGU Publishing House, 2010.-p. 119-121.

3. Baisov, A.Z. To the question of the need for marketing research of chondroprotective drugs /A.Z. Baisov, I.N. Andreeva, N.V. Gabrielyan // Actual problems of pharmaceutical. science and practice: Sat.

scientific tr. Vseros. scientific - pract. conf. October 28-30, 2009 - Vladikavkaz: Publishing House of SOGU, 2010.-S. 122-123.

4. Parfeinikov, S.A. Algorithm for marketing research of the pharmaceutical market of medicines / S.A. Parfeinikov, A.Z. Baisov, G.K. Ismailov; ed. M.V. Gavrilina // Development, research and marketing of new pharmaceutical products: Sat. scientific tr. - Pyatigorsk; Pyatigorsk GFA, 2010. - Issue. 65. - S. 540-541.

5. State and prospects for the development of the market for drugs used for the treatment and prevention of diseases of the musculoskeletal system using (an example of chondroprotectors) / T.M. Bondareva, A.Z. Baisov, I.N. Andreeva [and others] // Young scientists in solving actual problems of science: materials of the Intern. scientific-practical. conf. young scientists. - Vladikavkaz, 2011. - Ch. 1,-C. 164-167.

6. Andreeva, I.N. Analysis of the pharmaceutical market for chondroprotectors in the Stavropol Territory / I.N. Andreeva, A.Z. Baisov, A.I. Bylim // Topical issues of clinic, diagnostics and treatment in a multidisciplinary medical institution: materials of 10 scientific. conf. 20-21 Apr. 2011 - St. Petersburg, 2011. -S. 101-102.

7. State and development prospects of the market for chondroprotectors used to treat diseases of the musculoskeletal system (BCMS) / S.A. Parfeinikov, I.N. Andreeva, A.Z. Baisov [et al.] // Natural and technical sciences. -2011,-№4.-S. 295-298.

8. Ivashev, M.N. Chondroprotective pharmacotherapy: textbook. manual for the system of postgraduate education of pharmacists / M.N. Ivashev, A.B. Sergienko, A.Z. Baisov. - Pyatigorsk: Pyatigorsk GFA, 2008. - 292 p.

BAISOV AUBEKIR ZAURBEKOVICH

OPTIMIZATION OF THE RANGE OF MEDICINES USED IN DEGENERATIVE PROCESSES OF THE MUSCLE-MOTOR APPARATUS IN PHARMACEUTICAL ORGANIZATIONS OF THE STAVROPOL REGION

14.04.03 - organization of the pharmaceutical business

dissertations for the degree of candidate of pharmaceutical sciences

Signed to be hidden on 7^/^-2011. Paper format 60x84 1/16 Book and magazine paper. Rotaprint printing. Conv. oven l. 1.0. Circulation 100 copies. Order No.

State budgetary educational institution of higher professional education "Pyatigorsk State Pharmaceutical Academy". Ministry of Health and Social Development of the Russian Federation (357532, Pyatigorsk, Kalinin Ave.,

MINISTRY OF EDUCATION

STATE BUDGET EDUCATIONAL INSTITUTION OF HIGHER PROFESSIONAL EDUCATION "SIBERIAN

STATE MEDICAL UNIVERSITY" OF THE MINISTRY OF HEALTH AND SOCIAL DEVELOPMENT OF THE RUSSIAN FEDERATION

Analysis of complex dosage forms

Part 1. Dosage forms of pharmaceutical production

Tutorial

For self-training and a guide to laboratory classes in pharmaceutical chemistry for students of pharmaceutical faculties of universities of full-time and part-time education

UDC 615.07 (071) BBK R 282 E 732

E.V. Ermilova, V.V. Dudko, T.V. Kadyrov Analysis of complex dosage forms Part 1. Pharmaceutical production dosage forms: Uch. allowance. - Tomsk: Ed. 20012 . – 169 p.

The manual contains methods for the analysis of dosage forms of pharmaceutical production. It discusses the terminology, classification of dosage forms, provides regulatory documents that control the quality of medicines in pharmacy production, indicates the features of intra-pharmacy express analysis; the main stages of the analysis of dosage forms are described in detail, while special attention is paid to chemical control.

The main part of the manual is devoted to the presentation of material on the analysis of dosage forms: liquid (mixtures, sterile) and solid (powders), numerous examples are given.

The appendix contains extracts from orders, refractometric tables, information on indicators, forms of reporting journals.

For students of pharmaceutical faculties of higher educational institutions.

Tab. 21. Fig. 27. Bibliography: 18 titles.

Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . four

I. INTRODUCTION TO DOSAGE ANALYSIS

1.1. Terms used in pharmacy. . . . . . . . . . . . . . . . ………. 5 1.1.1. Terms characterizing medicines.. ….5 1.1.2. Terms characterizing dosage forms. . . ….5 1.2. Classification of dosage forms. . . . . . . . . . . . . . . . . . . . . . 7

1.3. Normative documents and requirements for the quality of medicines of pharmaceutical production. . . . . . . . . . . . . …...7 1.4. Peculiarities of express-analysis of medicinal products of pharmaceutical production. . . . . . . . . . . . . . . . . . . . . . . . . . ……………eight

1.4.1. Features of determining the authenticity of the express method. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ………..9

1.4.2. Features of quantitative express analysis. . . . . . . . …9

2.1. Organoleptic and physical control. . . . . . . . . . . . . . . . . . 10 2.1.1. Organoleptic control. . . . . . . . . . . . . . . . . . . . . . . . . . .10 2.1.2. Physical control. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10 2.2. Chemical control. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11 2.2.1. Tests for authenticity. . . . . . . . . . . . . . . . . . . . . . . . . . . . .11 2.2.2.. Quantitative analysis. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . fourteen

2.2.2.1. Ways of expressing concentrations. . . . . . . . . . . . . . . . .15 2.2.2.2. Methods of titrimetric analysis. . . . . . . . . . . . . . . 16 2.2.2.3. Calculation of the mass (volume) of the dosage form and the volume of the titrant for analysis. . . . . . . . . . . . . . . . . . . . . 17

2.2.2.4. Processing of measurement results. . . . . . . . . . . . . . . . . .19 2.2.2.5. Formulation of analysis results. . . . . . . . . . . . . . . . . . 32

III. ANALYSIS OF DOSAGE FORMS

Liquid dosage forms. . . . . . . . . . . . . . . . . . . . . . . . . . . . .33

3.1. Mixture analysis. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .33 3.2. Analysis of sterile dosage forms. . . . . . . . . . . . . . . . . . . . .59

Solid dosage forms

3.3. Powders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .89

Questions of self-training control. . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Test control. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125

Test control responses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .130

APPLICATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .131

Bibliography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .168

Foreword

The basis for writing the textbook was the program in pharmaceutical chemistry for students of pharmaceutical universities (faculties)

M.: GOU VUNMTS, 2003

One of the components of pharmaceutical analysis is the analysis of pharmacy and factory-produced drugs, carried out by the methods of pharmacopoeial analysis, according to the requirements of various guidelines,

manuals, instructions, etc.

The manual is devoted to the methods of research of dosage forms

(potions, sterile, powders) manufactured in a pharmacy, where all types of intra-pharmacy control are used, but the most effective is chemical control, which makes it possible to check the compliance of the manufactured dosage form with the prescription, both in terms of authenticity and quantitative content. Authenticity and quantitation procedures are presented in such a way as to use the best methods of investigation, and the minimum amount of drug was spent on the analysis.

The main part contains numerous examples of the use of refractometry in the quantitative analysis of drugs, since this method is widely used in pharmacy practice.

The proposed textbook contributes to the development of students' chemical analytical thinking.

I. INTRODUCTION TO DOSAGE ANALYSIS

1.1. Terms used in pharmacy

1.1.1. Terms characterizing medicines

Medicines - substances used for prevention

diagnosis, treatment of disease, prevention of pregnancy, derived from

biological technologies.

medicinal substance- a medicinal product, which is an individual chemical compound or biological substance.

medicinal product- a medicinal product in the form of a specific

dosage form.

Dosage form- a condition that is convenient for use in which the desired therapeutic effect is achieved is attached to a medicinal product or medicinal plant material.

1.1.2. Terms characterizing dosage forms

Powders are a solid dosage form for internal and external use, consisting of one or more crushed substances and having the property of flowability.

Tablets - a dosage form obtained by pressing drugs or a mixture of drugs and excipients, intended for internal, external, sublingual,

implantation or parenteral use.

Capsules - a dosage form consisting of a drug enclosed in a shell.

Ointments are a soft dosage form intended for application to the skin, wounds or mucous membranes and consisting of a medicinal substance and a base.

Pastes - ointments with a content of powdery substances over 20-25%.

Suppositories are a dosage form that is solid at room temperature and melts at body temperature.

Solutions liquid dosage form obtained by dissolving one or more medicinal substances intended for injection, internal or external use.

Drops liquid dosage form intended for internal or external use, dosed in drops.

Suspensions are a liquid dosage form containing, as a dispersed phase, one or more powdered medicinal substances distributed in a liquid dispersion medium.

Emulsions uniform in appearance dosage form,

consisting of mutually insoluble finely dispersed liquids,

intended for internal, external or parenteral use.

Extracts - concentrated extracts from medicinal plant materials. There are liquid extracts (Extracta fluida); thick extracts (Extracta spissa) - viscous masses with a moisture content of not more than 25%;

dry extracts (Extracta sicca) - free-flowing masses with a moisture content of not more than

Infusions dosage form, which is an aqueous extract from medicinal plant materials or an aqueous solution of dry or liquid extracts (concentrates).

Decoctions infusions that differ in the mode of extraction.

Aerosols dosage form in which drugs and excipients are under the pressure of a propellant gas

(propellant) in an aerosol can, hermetically sealed with a valve.

1.2. Classification of dosage forms

Classification of dosage forms is carried out depending on:

1.2.1. Aggregate state Solid : powders, tablets, dragees, granules, etc.

Liquid: true and colloidal solutions, drops, suspensions, emulsions,

liniments, etc.

Soft: ointments, suppositories, pills, capsules, etc.

Gaseous: aerosols, gases.

1.2.2. Quantities of medicinal substances

One-component

Multicomponent

1.2.3. Places of manufacture

Factory

Pharmacy

1.2.4. Manufacturing method

Solutions for injections Medicines Eye drops Decoctions Infusions Aerosols Infusions

Homeopathic remedies, etc.

1.3. Regulatory documents and quality requirements

medicines of pharmaceutical production

All production activities of the pharmacy should be aimed at ensuring high-quality manufacturing of medicines.

One of the most important factors determining the quality of medicines manufactured in a pharmacy is the organization of intra-pharmacy control.

Intra-pharmacy control is a set of measures aimed at the timely detection and prevention of errors that occur in the process of manufacturing, processing and dispensing medicines.

Pharmaceutical production drugs are subject to several types of control, depending on the nature of the dosage form.

The system of intra-pharmacy quality control of medicinal products provides for preventive measures, acceptance, organoleptic, written, questionnaire, physical, chemical and dispensing control.

According to the instructions of the Ministry of Health of the Russian Federation "On quality control of medicines manufactured in pharmacies" (Order No. 214 dated July 16, 1997), all medicines are subject to intra-pharmacy control: organoleptic, written and dispensing control - mandatory, questionnaire and physical - selectively, and chemical - in accordance with paragraph 8 of this order (see Appendix).

1.4. Features of express analysis of medicines

pharmacy production

The need for intra-pharmacy control is due to the corresponding high quality requirements for medicines manufactured in pharmacies.

Since the manufacture and distribution of drugs in pharmacies is limited to a short time, their quality is assessed by express methods.

The main requirements for express analysis are the consumption of minimal quantities of drugs with sufficient accuracy and sensitivity, simplicity and speed of execution, if possible, without separation of ingredients, the possibility of conducting an analysis without removing the prepared medicinal product.

If it is not possible to perform the analysis without separating the components, then the same separation principles are used as in macro analysis.

1.4.1. Features of determining the authenticity of the express method

The main difference between determining the authenticity of the express method from macro-analysis is the use of small amounts of the studied mixtures without separating them.

The analysis is performed by the drip method in micro-test tubes, porcelain cups, on watch glasses, while 0.001 to 0.01 g of powder or 15 drops of the test liquid are consumed.

To simplify the analysis, it is sufficient to carry out one reaction for a substance, and the simplest, for example, for atropine sulfate, it is enough to confirm the presence of a sulfate ion, for papaverine hydrochloride - a chloride ion by classical methods.

1.4.2. Features of quantitative express analysis

Quantitative analysis can be performed by titrimetric or physico-chemical methods.

Titrimetric express analysis differs from macro-methods in the consumption of smaller quantities of analyzed preparations: 0.05 0.1 g of powder or 0.5 2 ml of solution, and the exact mass of the powder can be weighed on a hand-held scale; to improve accuracy, dilute solutions of titrants can be used: 0.01 0.02 mol/l.

A weighed portion of a powder or a volume of a liquid dosage form is taken in such a way that 1–3 ml of the titrant solution is used for the determination.

Of the physicochemical methods in pharmacy practice, the economical method of refractometry is widely used in the analysis of concentrates,

semi-finished products and other dosage forms.

II. MAIN STAGES OF PHARMACEUTICAL ANALYSIS

2.1. Organoleptic and physical control

2.1.1. Organoleptic control

Organoleptic control consists in checking the dosage form for the following indicators: appearance (“Description”), smell,

homogeneity, absence of mechanical impurities. The taste is checked selectively, and dosage forms prepared for children - everything.

Uniformity of powders, homeopathic triturations, ointments, pills,

suppositories are checked before dividing the mass into doses in accordance with the requirements of the current State Pharmacopoeia. The check is carried out selectively at each pharmacist during the working day, taking into account the types of dosage forms. The results of organoleptic control are recorded in the journal.

2.1.2. Physical control

Physical control consists in checking the total mass or volume of the dosage form, the number and mass of individual doses (at least three doses),

included in this dosage form.

This checks:

Each series of packaging or intra-pharmaceutical blanks in the amount of at least three packages;

Dosage forms manufactured according to individual prescriptions (requirements), selectively during the working day, taking into account all types of dosage forms, but not less than 3% of the number of dosage forms manufactured per day;

Introduction

1. Tasks and functions of a hospital pharmacy. Its features

Conclusion

The history of pharmacy, as a pharmacy business, is inextricably linked with the activities of hospital pharmacies. The first hospital pharmacy was a pharmacy at the hospital, set up by Patriarch Nikon and maintained by the monastic income.

Reliable information about the existence of hospital (hospital) pharmacies appears only at the beginning of the 18th century, when, after Peter the Great traveled to Western Europe, he decided to open the first hospital in Russia for the population.

The Moscow General Hospital was opened on November 21, 1707. Almost immediately, a pharmacy garden was set up at the hospital, and in the summer the pharmacist was obliged to walk with his students out of town, around Moscow, to collect and disassemble medicinal plants. In medical practice, galenical preparations were mainly used. Tinctures, spirits, elixirs and highly complex decoctions were preferred to simple medicines. Recipes were made up of 20-30 ingredients.

The first Russian hospital charter, drawn up in Russia and approved by Empress Anna on December 24, 1735, contained requirements for the organization of the pharmacy business and the process of manufacturing medicines in hospital pharmacies: it is possible to compose ... also in this laboratory, wine is doubled and infused with certain herbs, which is given to him; both cubes and boilers are bought from the hospital amount; moreover, in the hospital, he should look at those who boil dococts for the sick, so that they are properly boiled and kept clean: also keep all apothecary utensils clean and in good storage, so that nothing is lost in vain.

The requirements prescribed in the hospital charter have not lost their relevance at the present time. Today it is difficult to imagine the work of a modern medical institution without such a unit as a pharmacy.

The close proximity of the hospital pharmacy to the hospital creates optimal conditions for drug provision of the treatment process. However, the legislative framework in the field of hospital pharmaceutical activity has not yet been created.

The Federal Law of the Russian Federation No. 86-FZ of June 22, 1998 “On Medicines” provides a clear definition of pharmaceutical activity. At the same time, the main function of hospital pharmacies related to the provision of drugs to hospitals is not included in the legislative definition of pharmaceutical activity.

Today there is no defined standard of hospital pharmacy. The regulation on the pharmacy of health care facilities was approved by order of the Ministry of Health of the Russian Federation of August 18, 1972 No. 689. Approximate norms for the technical and economic equipment of pharmacies were approved by order of the Ministry of Health of the Russian Federation of December 31, 1971 No. 949. States for self-supporting interhospital (hospital) pharmacies are calculated in accordance with by order of the Ministry of Health of the Russian Federation of 06.23.1983 No. 758. Accounting for the movement of medicines and medical devices in pharmacies of healthcare facilities is carried out in accordance with the order of the Ministry of Health of the Russian Federation of 02.06.1987 No. 747.

All these regulatory documents need to be updated and brought into line with new legislative acts in the field of drug circulation.

Noteworthy is the order of the Ministry of Health and Social Development of Russia No. 319 dated May 3, 2005, which regulates the “hospital pharmacy” among and types of pharmacy organizations. This order laid the foundation for modern state regulation of the activities of hospital (inter-hospital) pharmacies.

Relevance of the topic. The problem of hospital pharmacy today is more acute than all others, since this sector is now at a more backward level compared to other segments of the industry.

The regulatory framework governing the work of hospital and interhospital pharmacies was created in the 70-80s in a country with a different economy. Currently, there are no standards for the operation of hospital pharmacies, and a licensing system for hospital pharmacies has not yet been prescribed. A big problem is the limited staffing: for every 300 beds - 1 position of a pharmacist or pharmacist. For successful work, the certainty of the functions of the pharmacy of a healthcare institution is necessary, there is no specialty "hospital pharmacy" and the role of hospital pharmacy as a whole is underestimated. The role of hospital pharmacies needs to be considered in the overall context of quality care.

hospital pharmacy medicinal injectable

There are 2 types of pharmacies:

Open type, which serves both individuals and medical institutions;

Closed type - pharmacies at medical institutions ("hospital" pharmacies), which carry out only production functions, manufacturing medicines only for patients who are being treated in hospitals.

The main tasks of the hospital pharmacy are:

Provision of medical institutions according to their requirements with medicines and medical products of the pharmacy assortment;

Identification of the need for medicines and medical products of the pharmacy range in accordance with the profile and specifics of the work of medical institutions;

Organization of systematic information of doctors of attached institutions about medicines and medical products of the pharmacy assortment;

Fulfillment of planned targets and ensuring strict observance of state discipline.

In order to fulfill these necessary tasks, the pharmacy must perform certain functions, which are as follows:

Ensures the implementation of established targets;

Carries out timely supply of medical institutions with medicines and other medical products of the pharmacy assortment;

Analyzes the needs of medical institutions for medicines and medical products of the pharmacy assortment, draws up and submits requirements and applications-orders for the current and future needs for medicines and other medical products of the pharmacy assortment;

Produces the preparation of medicines at the request of the attached institutions and controls their quality;

Carries out systematic control over the correct storage and consumption of medicines and medical products of the pharmacy range in the subdivisions of attached institutions;

Ensures compliance with all requirements of the pharmaceutical order and sanitary regime;

Provides doctors with all the necessary information about medicines, their pharmacological effects, side effects, dosages, etc.;

Ensures the storage of medicines and other medical products of the pharmacy range in accordance with the requirements of the current State Pharmacopoeia and established rules;

Carries out accounting, operational and statistical accounting, draws up reports and submits them in accordance with the established procedure and terms;

Ensures the introduction of advanced methods and scientific organization of labor in the work of personnel.

The hospital pharmacy is mostly a manufacturing pharmacy, a pharmaceutical factory in miniature. Currently, the production function of hospital pharmacies is of particular social importance due to the fact that:

The pharmaceutical industry cannot focus on the needs of a single medical institution (HCI) and produces a limited number of infusion solutions;

The hospital pharmacy is able to flexibly vary the range of medicines in accordance with the profile and requests of the healthcare facility;

It is possible to select the individual composition and dosage of medicines, taking into account the characteristics of the patient's condition, concomitant diseases (i.e., manufacturing according to unified prescriptions), as well as to produce dosage forms for children;

The length of time between the preparation of medicines in a hospital pharmacy and its use in health facilities is reduced. This is very important, since some preparations do not withstand a long shelf life and require the introduction of special preservatives. Long-term storage may lead to a decrease in the activity of the main components;

Manufactured drugs have a lower cost compared to industrial drugs and imported drugs, which makes them accessible to low-income segments of the population.

Preserving the production functions of hospital pharmacies while ensuring the economic efficiency of economic and financial activities necessitates the consideration of a set of problems associated with the manufacture of medicines, which include:

Decreased profitability of hospital pharmacies due to increased distribution costs;

Low tariffs for the manufacture of medicines;

Weak technical equipment of hospital pharmacies;

Loss of specialists moving to organizations with a higher level of remuneration;

Late payment by medical institutions for medicines received from pharmacies.

In this regard, there is a need for fundamentally qualitative changes in the very process of providing this type of pharmaceutical assistance, in developing recommendations for improving the economic efficiency of financial and economic activities.

Hospital and interhospital pharmacies, being legal entities, are much freer in the formation of staffing levels and the organization of procurement of medicines. However, their activities should also be regulated by industry standards, since the standard for completely legal retail trade is also difficult to apply in the work of UZ pharmacies due to their specifics.

Around the world, hospital pharmacy innovations follow general trends in medical services. Basically they are:

Innovations in the provision of drug information as treatments become more complex;

Participation in the control of quality and cost of treatment, which is increasingly based on data from clinical trials;

Greater attention to the patient and the desire of pharmacists to participate in the management of individual patients.

In different countries, these changes occur in different ways. There is little definite information on specific steps in different countries, but certain trends can be identified that influence this.

2. Assortment of medicines in the hospital pharmacy

Hospital pharmacies are essential and should be in every clinic. Today they are at every hospital. Any stationary institution should have its own pharmacy of ready-made medicines, a room for storing medicines and a specialist. This would make it possible to strictly comply with the storage conditions for finished dosage forms and maintain a professional approach to working with drugs.

The list of essential medicines is the standard treatment for each nosology. It follows from this that each medical and preventive organization must necessarily have standards for the treatment of diseases of its contingent of patients.

Hospital pharmacies differ significantly from conventional green cross facilities, both in function and in the nature of their activities. The task of HCI pharmacies is to meet the needs of the medical process in pharmaceutical goods and services. Therefore, certain tasks are set for pharmacies at hospitals:

Provide medicines for the treatment process both in the provision of free medical care and paid services;

Provide medical staff with professional information about medicines;

Organize pharmaceutical supervision in the hospital.

Hospital pharmacies play an important role in the drug supply of medical institutions. An analysis of the nomenclature of some hospital pharmacies shows that a significant part of the pharmacy dosage forms are sterile dosage forms: solutions for injections, eye drops, as well as sterile dosage forms for external use. These dosage forms are prepared in a pharmacy in large volumes.

Thus, an isotonic sodium chloride solution is produced in an amount of more than 200 liters per shift. It should be noted the low cost of pharmaceutical dosage forms. For example, the cost of isotonic sodium chloride solution in a hospital pharmacy is almost six times cheaper than commercial production.

Prepared in large quantities in pharmacies furatsilina solutions on isotonic sodium chloride solution and without it. Such solutions of furacilin of the pharmaceutical industry are not produced. Among the dosage forms for internal use are common potions with motherwort of various compositions, Pavlov's mixture, cough mixtures with thermopsis and marshmallow of various compositions, as well as one-component solutions of calcium chloride 5 and 10%, potassium iodide 0, 25 and 3%, magnesium sulfate 33% and others.

Pharmacy prescriptions also contain water extracts, which can be used both for internal and external use, in particular for inhalation. An example of the first is breast collection, the second is an infusion of chamomile, peppermint, decoctions of wild rosemary, pine buds.

External dosage forms are represented by numerous ointments, such as simple sulfuric ointments of various concentrations, Lassar paste, zinc and packaged powdered medicinal substances - powders.

A special group is one-component solutions for electrophoresis. Their range is quite diverse - solutions of papaverine hydrochloride 2%, nicotinic acid 2%, novocaine 2%, potassium iodide 1 and 3%, etc. Suppositories are rarely found in the formulation of pharmacies. An analysis of the formulation and work of hospital pharmacies showed that the range and production volumes not only do not decrease, but also increase.

In the event of emergencies, the workload of hospital pharmacies can increase dramatically, especially for groups of sterile medicines. In the future, hospital pharmacies will have to switch to the manufacture of medicines in accordance with GMP rules, so now it is necessary:

Bring production facilities into an appropriate condition;

Implement complexes for obtaining purified water and water for injection using the reverse osmosis method;

Make wider use of membrane technologies;

Purchase high-quality and productive sterilizers;

Conduct staff training in accordance with the specified rules.

3.Features of drug technology in a hospital pharmacy

If we consider the performance of production functions by hospital (hospital) pharmacies as an important component of their activities, then the most rational way out may be the following:

Organization of small-scale production using small-sized automatic lines and other types of equipment that meets GMP requirements;

Creation of mobile autonomous complexes for the production of sterile solutions in the field, which is relevant for medical units of the Ministry of Defense and the Ministry of Emergency Situations.

In the conditions of hospital (hospital) pharmacies, the share of sterile solutions accounts for about 70%, annually measured by tens of thousands of vials of the entire extemporaneous formulation. Sterile dosage forms require not only special manufacturing conditions, but also significant labor and time costs.

Solutions for injection should be prepared from medicinal substances that fully meet the requirements of private articles of the GF X or other scientific and technical documentation. In some cases, special purification of medicinal substances intended for injection is provided. Glucose, calcium gluconate, sodium caffeine-benzoate, sodium citrate, quinacrine, calcium chloride, magnesium sulfate and some others should have an increased degree of purity.

Auxiliary substances (stabilizers, solubilizers, preservatives, etc.) must also comply with the private articles of the GF X (if these substances are official) or other scientific and technical documentation in terms of quality.

Among injectable solutions in hospital pharmacies, a special group is isotonic solutions, which are solutions with an osmotic pressure equal to the osmotic pressure of body fluids: plasma, blood, lacrimal fluid, lymph, etc. Solutions with a lower osmotic pressure are called hypotonic, with a large one - hypertonic.

The isotonicity of injectable solutions is very significant. Solutions that deviate from the osmotic pressure of the blood plasma cause a pronounced sensation of pain, and it is the stronger, the sharper the osmotic difference.

With the introduction of anesthetics (in dental and surgical practice), osmotic trauma causes sharp pain after anesthesia, lasting for hours. Sensitive tissues of the eyeball also require isotonization of the applied solutions. Introductions into the spinal canal should also not cause an osmotic jump. The osmotic pressure of blood and lacrimal fluid is normally kept at the level of 72.52-104 N/m2 (7.4 atm).

Technology for the manufacture of injection solutions. As solvents for the preparation of injection solutions, water for injection, peach and almond oils are used. Injection solutions must be clear. They are prepared by mass-volume method: the medicinal substance is taken by mass (weight), the solvent - to the required volume. The quantitative determination of medicinal substances in solutions is carried out according to the instructions in the relevant articles.

Source drugs must meet the requirements of GF X. Calcium chloride, caffeine-sodium benzoate, hexamethylenetetramine, sodium citrate, as well as magnesium sulfate, glucose, calcium gluconate and some others must be used in the form of a grade "for injection" with a high degree of purity.

In order to avoid contamination with dust, and with it the microflora, preparations used for the preparation of injection solutions and aseptic drugs are stored in a separate cabinet in small jars, closed with ground glass stoppers, protected from dust by glass caps. Strict observance of technology is required.

Toxic substances necessary for the preparation of injectable drugs are weighed by the inspector in the presence of an assistant and are immediately used by the latter for the preparation of the drug. When receiving a poisonous substance, the assistant is obliged to make sure that the name of the barbell corresponds to the purpose in the recipe, as well as that the set of weights and weighing are correct.

For all, without exception, injectable medicines prepared by an assistant, the latter is obliged to immediately draw up a control passport (coupon) with the exact indication of the names of the ingredients of the medicine taken, their quantities and personal signature.

All injectable medicines must be subjected to chemical control for authenticity before sterilization, and if there is an analytical chemist in the pharmacy, to quantitative analysis. Solutions of novocaine, atropine sulfate, calcium chloride, glucose and isotonic sodium chloride solution under any circumstances must be subject to qualitative (identification) and quantitative analysis.

In all cases, injectable drugs should be prepared under conditions of the least possible contamination of the drug with microflora (aseptic conditions). Compliance with this condition is mandatory for all injectable drugs, including those undergoing final sterilization.

Rp.: Sol. Calcii chloridi 10% 50.0

D.S. intravenous injection

To prepare the injection solution, sterilized utensils are needed: a dispensing bottle with a stopper, a volumetric flask, a funnel with a filter, a watch glass or a piece of sterile parchment as a roof for the funnel. To prepare a solution of calcium chloride for injection, you also need a sterilized graduated pipette with a pear to measure a concentrated solution of calcium chloride (50%). Before preparing the solution, the filter is repeatedly washed with sterile water, the dispensing bottle and stopper are washed and rinsed with filtered water.

Measure (or weigh out) the required amount of the drug substance, wash it into a volumetric flask, add a small amount of sterile water, then bring the volume of the solution to the mark. The prepared solution is filtered into a tempering flask. The vessel with the solution and the funnel during filtration are closed with a watch glass or sterile parchment. Examine the solution for the absence of mechanical impurities. After capping the vial with the injection solution, tightly tie the cork with wet parchment, write the composition and concentration of the solution on the piping, put a personal signature and sterilize the solution at 120°C for 20 minutes.

In pharmacy practice, bottles of the appropriate capacity are used to dispense sterile solutions. It is essential that they be of neutral grade glass to avoid leaching and precipitation and other undesirable changes in solutions. In some cases, containers made of glass AB-1 (slightly alkaline) are allowed.

Vials used for dispensing injection solutions must be checked for chemical stability according to certain methods. Vials for sterile solutions should be with well ground stoppers. Ordinary cork stoppers that form dust and transfer coloring and extractive substances into the solution are not allowed.

It is allowed to use rubber stoppers, previously sterilized by prolonged boiling in water. In hospital pharmacies, when sterile solutions are prepared for immediate use, the bottles are allowed to be sealed with a swab of non-defatted sterile cotton wool tied with sterile parchment. A piece of sterile gauze should be placed under the swab. M.I. Mamaychuk and V.A. Brailovskaya proved the possibility of capping bottles with sterile solutions with rubber and polyethylene caps, which allow taking the solution with a syringe by piercing the cap with a needle without violating the sterility of the solution.

A more perfect form of dispensing sterile solutions from the pharmacies of medical institutions to the hospital department is the dispensing in standard wide-mouth bottles of various capacities with a standard rubber stopper fixed with a crimped aluminum cap, similar to antibiotic vials.

Potions. Pavlova's mixture is a complex preparation containing caffeine-sodium benzoate - 0.2 g, sodium bromide - 0.2 g, distilled water - 200 ml. Doses of the components of Pavlov's mixture may vary depending on the characteristics of the higher nervous activity of the patient and are determined by the doctor. The medicine is produced in glass bottles of 200 ml. The drug regulates higher nervous activity. Has a calming effect.

Rp .: inf. herbaeThermopsidis0,1 - 200 ml

Natriihydrocarbonatis

Liq. Ammonii anisati aa 1.0

Sirupi Althaeae 20ml

M.D.S. 1 tablespoon 3 times a day.

The total volume of the mixture is 221 ml. In its manufacture, a dry extract of thermopsis (1: 1) is used, which is placed in a stand in an amount of 0.1 g and dissolved in 170 ml of water. The resulting solution is filtered into a dispensing bottle, in which 20 ml of a 5% solution of sodium bicarbonate (1:20) and 10 ml of a 10% solution of sodium benzoate (1:10) are previously placed. Pre-mixed 20 ml of marshmallow syrup and 1 ml of ammonia-anise drops are added to the mixture.

Pharmacy manufacturing of medicines for hospitals remains relevant today, especially for hospitals - after all, the existing range of industrial medicines cannot fill the entire spectrum of medicines that patients need, especially since there are those that are not produced by the industry at all due to various reasons. This is, first of all, drugs needed for children and newborns .

The first group of drugs manufactured in a hospital pharmacy are sterile solutions for internal use by newborns. These solutions are prepared under aseptic conditions, purified water is used as a solvent, then the solution is sterilized. In solutions for injections and infusions for feeding newborns, the presence of stabilizers is unacceptable. The only exception is 0.25% novocaine solution.

Glucose solution 5, 10, 25% is prepared for newborns without a stabilizer. They cannot be replaced by infusion solutions of the same concentration, since the latter include the Weibel stabilizer - a solution of HCl and NaCl - and its pH is 3-4. The shelf life of glucose solutions for drinking newborns is only 1 month. For example, a common prescription for newborns: glucose solution 10% or 20% - 100.0, glutamic acid - 1.0 g in the factory industry, such a drug is not available.

Dibazol solution is also not applicable for internal use in the treatment of newborns, since the factory preparation contains hydrochloric acid.

There is another group of substances that can only be made in pharmacies - solutions for medicinal electrophoresis, the essence of which is reduced to therapeutic effects on the patient's body of an electric current and the introduction of this effect into the tissues of the patient's medicinal substance. Electrophoresis is widely used in various areas of health care, in most medical and treatment-and-prophylactic institutions: in sanatoriums, clinics, women's clinics and in all hospitals.

Electrophoresis requires aqueous solutions of medicinal substances: analgin, dibazol, diphenhydramine, papaverine, ichthyol, zinc sulfate, potassium chloride and many others. In this case, preservatives cannot be used due to their electrical non-indifference. As of today, industrial dosage forms for electrophoresis do not exist.

Hospital pharmacies also produce ointments. Pasta Lassara is in great demand. This is a homogeneous ointment of yellowish color, thick consistency. In a thin layer of paste rubbed on paper, when viewed with the naked eye, grains should not be detected.

Expenditure rates. To prepare 1 kg of Lassara pasta, you need:

Vaseline 480.5 g

Salicylic acid 19.9

Wheat starch 251.2

Zinc oxide 251.2

Technological process. Salicylic acid, starch and zinc oxide are crushed by sifting each powder separately through a No. 2 sieve.

Vaseline is loaded into a digester with a steam jacket and melted at a temperature of 50 - 55 ° C, then passing it through the canvas.

About half of the required amount of petroleum jelly is placed in a mixing kettle and thoroughly mixed with zinc oxide and salicylic acid. Then the sifted starch and the rest of the vaseline are introduced into the boiler in parts, everything is thoroughly mixed until the mass is completely homogeneous.

The ointment from the mixing boiler is passed through the mazeter until the smallest grains disappear (the OTK controller takes a sample for analysis).

Gray mercury ointment is an emulsion in which liquid metallic mercury is dispersed in a base. To obtain this ointment, it is necessary to expend a significant amount of mechanical energy, because mercury has a very high surface tension.

The ointment should be a completely homogeneous mass containing 30% metallic mercury. When examining an ointment rubbed in a thin layer on glossy paper, individual droplets of mercury should not be visible even through a magnifying glass.

Technological process. The entire manufacturing process is divided into the following main stages:

Making concentrated mercury ointment;

Preparation of the fat base;

Mixing mercury concentrate with a fat base;

Packing and storage.

Making concentrated mercury ointment. To make a concentrate, take 85 parts of mercury and 15 parts of anhydrous lanolin.

Depending on the amount of ointment produced, mortars of various sizes are used, which have a special device. Small mortars, as a rule, are cast iron, and large ones are stone (agate). The pestles during operation perform a double planetary motion: they rotate around their own axis and around the center of the mortar. 15 parts of anhydrous lanolin are placed in a mortar, then 85 parts of mercury are added in small portions. Grinding is continued for 14-18 hours, after which an average sample is taken to determine the homogeneity and percentage of mercury content. In pharmacies, the fat base is added to the concentrate as needed, since during long-term storage, fatty acids are released from fats, which form toxic compounds with mercury. With a lack of lanolin, the concentrate is sometimes made on a special emulsion base obtained from zinc oxide, vegetable oil and water.

It is obvious that the future fate of HCI pharmacies requires the speedy development of the industry standard "Pharmacy of Health Care Institutions", the exact procedure for licensing pharmaceutical activities in health care institutions. It is necessary to develop criteria for the compliance of pharmaceutical activities with established rules and a regulation on the pharmacist of a hospital pharmacy.

It is also necessary to change the regulatory framework for calculating the staffing of the pharmaceutical staff of hospital pharmacies and develop regulatory documents that meet the new requirements for pharmacies of health care facilities.

There are about 70 thousand pharmaceutical enterprises in Russia. These are special organizations that, by the nature of their activities, must ensure the quality of drug care and its accessibility to the population. Performing the functions of drug supply, pharmacy enterprises conduct economic activities. Of great importance is the legislative regulation of both general economic and pharmaceutical aspects of the activities of pharmacy enterprises, especially hospital pharmacies. The regulatory framework is very extensive, but today the law “On Technical Regulation” is becoming increasingly important, which will play a huge role in the future.

The problem of hospital pharmacy today is more acute than all others, since this sector is now at a more backward level compared to other segments of the industry.

Currently, there are no standards for the activities of hospital pharmacies, so far there is no system for licensing hospital pharmacies (they are not legal entities, and only legal entities are subject to licensing). To obtain a license, a pharmacy must be registered in the charter of a medical institution, this does not always happen, and now a number of hospital pharmacies operate without a license at all.

Traditionally, there are four functions of the HCI pharmacy:

Acceptance of requirements for medicines;

Preparation of medicines;

Control of their quality;

Vacation in the departments of health care facilities.

However, these functions are clearly not enough. In particular, it is necessary to control the storage of medicines in the departments, informing medical workers about the medicines available in the pharmacy, etc.

To optimize the process of dispensing medicines, it is necessary to introduce intra-pharmacy packaging and dispense already packaged medicines to departments. It is necessary to keep personalized records in medical institutions.

Pharmacy regulation aims to ensure the quality of drug care, which includes the quality of the product itself, the quality of the facility, equipment and the quality of the implementation process.

In connection with the commercialization of the activities of pharmacies and the appearance on the shelves of pharmacies of falsified and counterfeit products, the development of a system for regulating pharmacy activities is of particular relevance.

The pharmaceutical order is a set of requirements for the premises, personnel, sanitary regime, storage conditions, forms of service, dispensing rules, input control of medicines, and other indicators that ensure the quality of drug care provided in a particular pharmacy enterprise, regulated by regulatory legal acts of the Russian Federation.

An analysis of the process of providing drug care allows us to propose a triad of quality assurance for the provision of this care by a pharmacy enterprise:

The quality of the premises (a set of premises, the design of the trading floor, equipment, compliance with the rules of the sanitary regime);

The initial quality of medicines (availability of documents confirming their quality, compliance with storage rules, control over expiration dates, etc.);

Quality of implementation (required staff qualifications, high-quality assortment, compliance with the holiday rules, information services, pricing, documentation).

These three main points will form the basis of the technical regulation on the retail trade in medicines, which is currently being prepared.

The elements of the pharmaceutical order are personnel, premises, acceptance of medicines, dispensing, medicines themselves, sanitary regime, working hours, information system, etc.

Bibliography

1. Weekly "Apteka" No. 42, 2004.

2. Weekly "Apteka" No. 22, 2005.

3.Internet: www. medical com.ua

4. Bulletin of Pharmacy, 2005.

5. Magazine "Pharmacist" No. 16,2004.

6.Interent: www. provizor. kharkov. ua.

7. Besedina I.V., Griboedova A.V., Korchevskaya V.K. Improving the conditions for the preparation of injection solutions in a pharmacy in order to ensure their apyrogenicity // Pharmacy.- 1988.- No. 2.- p. 71-72.

8. Besedina I.V., Karchevskaya V.V. Evaluation of the purity of injection solutions of pharmaceutical manufacture in the process of application // Pharmacy.- 1988.- No. 6.- p. 57-58.

9. Gubin M.M. Problems of manufacturing injection solutions in industrial pharmacies // Pharmacy. - 2006. - No. 1.

10.Moldover B.L. Aseptically manufactured dosage forms St. Petersburg, 199

11. Svetlanova S. Without a hospital pharmacy, the healing process will stop. // Pharmaceutical Bulletin. - 2005. - No. 26 (389) of August 16, 2005.

12.www.medkurs.ru/pharmacy/sterile_medicine/section2315/11725.html

13. Avamesyants E. M. Technology for the manufacture of dosage forms. Rostov-on-Don, "Phoenix", 2002.

14. State Pharmacopoeia of the USSR. – 10th ed. Moscow: Medicine, 1968.

15. Klimova L.D., Ber O.V. Making medicines. Educational-methodical recommendations. - Samara; GOUVPO SamGMU Roszdrav, 2006. - 70 p.

16. Order of the Ministry of Health of the Russian Federation of December 31, 1971. No. 949

17. Order of the Ministry of Health of the Russian Federation of 18.08.1972 No. 689

18. Order of the Ministry of Health of the Russian Federation of 06/23/1983. No. 758

19. Order of the Ministry of Health of the USSR No. 758 dated 06/23/1983 "On the position and states of self-supporting interhospital (hospital) pharmacies"

Liquid dosage forms are dispersed systems in which drugs (solid, liquid and gaseous) are distributed in a liquid dispersion medium. Depending on the degree of grinding of the dispersed phase (DP) and the nature of its connection with the dispersion medium, liquid dosage forms can be: true solutions; solutions of macromolecular compounds; colloidal solutions; suspensions; emulsions; combinations of these types of dispersed systems (combined systems).

Liquid dosage forms include:

Solutions (drops, solutions for injection, etc.) - dosage forms obtained by dissolving liquid, solid or gaseous substances in an appropriate solvent;

Suspensions (suspensions) - dosage forms, which are a dispersed system containing one or more solid drugs suspended in an appropriate liquid (particle size ranges from 0.1 to 10 microns); suspensions are used for internal and external use, as well as for injection;

Emulsions - a dosage form, which is a dispersed system containing two or more mutually insoluble or immiscible liquids, one of which is emulsified into the other; emulsions are used for internal and external use, as well as for injection;

Infusions and decoctions - water extracts from medicinal plant materials or aqueous solutions of extracts;

Mucus - dosage forms of high viscosity, as well as those prepared using starch from an aqueous extract of plant materials;

Medicinal syrups - a dosage form for internal use, which is a concentrated solution of various sugars, as well as their mixtures with drugs;

Tinctures - dosage form, which is alcohol and water-alcohol extracts from medicinal plant materials, obtained without heating and removing the extractant;

Extracts - concentrated extracts from medicinal plant materials or raw materials of animal origin, which are mobile, viscous liquids or dry masses; distinguish between liquid extracts (mobile liquids), thick extracts (viscous masses with a moisture content of not more than 25%), dry extracts (loose masses with a moisture content of not more than 5%).

Liquid dosage forms account for more than 60% of the number of drugs prepared in pharmacies.

The preparation of liquid dosage forms is regulated by the order of the Ministry of Health of the Russian Federation No. 308 dated 10/21/1997, according to which solutions and other liquid dosage forms are manufactured by methods: mass-volume, by mass, by volume. The current GF is adopted as the main mass-volume method for the manufacture of liquid dosage forms.

Mass-volume concentration- mass of the drug or individual substance (g) in the total volume of the liquid dosage form (ml).

Mass concentration- mass of the drug or individual substance (g) in the total mass of the liquid dosage form (g).

Volume concentration- the volume of a liquid drug or an individual substance (ml) in the total volume of a liquid dosage form (ml).

Examples

In prescriptions:

Rp.: Solutionis Natrii bromidi 2% - 200 ml (a) Rp.: Solutionis Camphorae oleosae 2% - 50.0 (b) Rp.: Solutionis Acidi hydrochlorici 2% - 200 ml (c).

As can be seen from the example, mass-volume concentration (a), mass concentration (b) and volume concentration (c) can be indicated as a percentage (%).

In addition, it is possible to separately enumerate the mass and volume of the drug (substance) and the dispersion medium (solvent):

Rp.: Natrii bromidi 4.0

Aquae purificatae 200 ml (a)

Rp.: Camphorae 1.0

Olei Helianthi 49.0 (b)

Aquae purificatae 196 ml (c); indicating the solvent to a given volume or mass:

Rp.: Natrii bromidi 4.0

Aquae purificatae ad 200 ml (a)

Rp.: Camphorae 1.0

Olei Helianthi ad 50.0 (b)

Rp.: Acid hydrochlorici 4 ml

Aquae purificatae ad 200 ml (c); indicating the ratio of the mass or volume of the dissolved drug (substance) and the volume or mass of the solution:

Rp.: Solutionis Natrii bromidi ex 4.0 - 200 ml

(seu 1:50 - 200 ml) (a)

Rp.: Solutionis Camphorae oleosae ex 1.0 - 50.0 (b) Rp.: Solutionis Acidi hydrochlorici ex 4 ml - 200 ml (seu 1:50 - 200 ml) (c). Mass-volume concentration is used for:

Production of aqueous and water-alcohol solutions of solid drugs;

Aqueous and water-alcohol suspensions with a solids content of less than 3%;

Dilution of standard solutions written in the prescription under the chemical name, indicating the concentration of the drug in the solution.

In concentration by weight, solutions of solid and liquid drugs are prepared in viscous and volatile solvents, dosed by weight, as well as suspensions and emulsions and homeopathic liquid drugs. The following are dosed by weight: fatty and mineral oils, glycerin, dimexide, polyethylene glycols (polyethylene oxides), silicone fluids, ether, chloroform, as well as benzyl benzoate, validol, vinylin (Shostakovsky's balm), birch tar, ichthyol, lactic acid, essential oils, turpentine, methyl salicylate, nitroglycerin, perhydrol.

Volumetric concentration is used in the manufacture of:

Alcohol solutions of various concentrations;

Solutions of hydrochloric acid;

Standard solutions written out in the prescription under the conditional name;

Purified water and water for injection;

Aqueous solutions of drugs;

Galenic and novogalenic drugs (tinctures, liquid extracts, etc.).

If the recipe does not specify a solvent, then an aqueous solution is made. Under the name “water”, in the absence of special instructions, purified water is understood. The term "alcohol" refers to ethyl alcohol. In the absence of instructions on the concentration of alcohol (in the recipe or the corresponding ND), 90% alcohol should be used. The name "ether" means medical ether. The term "glycerol" means glycerin containing 10-16% water, with a density of 1.223-3.233 g/cm 3 .

In the manufacture of aqueous solutions of substances containing water of crystallization as part of the molecule, the recalculation of the amount of drugs, taking into account the content of crystallization water, is carried out in accordance with the current Global Fund or other ND in cases where this is regulated by the composition of the recipe and the method of quantitative determination. Strongly hygroscopic substances are used for the manufacture of liquid dosage forms in the form of concentrated solutions (for example, calcium chloride).

Liquid dosage forms are subjected to chemical control - qualitative or complete chemical, depending on the composition and purpose. According to the order of the Ministry of Health of the Russian Federation No. 214 dated July 16, 1997, a qualitative analysis is mandatory: concentrates, semi-finished products and liquid drugs in a burette installation and in barbells with pipettes in the assistant's room when filling.

Qualitative analysis is subjected to selectively the following groups of drugs.

Dosage forms manufactured according to individual prescriptions or requirements of healthcare facilities selectively, but not less than 10% of the total number of prescriptions. Particular attention is paid

on dosage forms for children, especially newborns, as well as those used in eye practice and containing poisonous and narcotic substances.

Mandatory full chemical analysis is carried out: all solutions for injections and infusions before sterilization, including the determination of the pH value, isotonizing and stabilizing substances; solutions for injections and infusions after sterilization are checked for pH value, authenticity and quantitative content of active substances; sterile solutions for external use; eye drops and ointments containing narcotic and poisonous substances; dosage forms for newborns; solutions of hydrochloric acid for internal use, atropine sulfate, silver nitrate; concentrates, semi-finished products, triturations, intra-pharmaceutical preparations, stabilizers and buffer solutions; the concentration of ethyl alcohol when diluted in a pharmacy.

Complete chemical control is subject to selective: dosage forms manufactured in a pharmacy according to individual prescriptions or requirements of medical organizations (at least 3 when working in one shift); dosage forms for children; used in eye practice; containing narcotic and poisonous substances; solutions for therapeutic enemas.

The results of qualitative and complete chemical control are recorded in journals (see Appendix 2). The journal also records cases of unsatisfactory manufacture of drugs found during the quality control of their manufacture in a pharmacy by pharmacists-analysts of the center for quality control of drugs. The detected marriage is seized for re-analysis with the preparation of an act of seizure and an explanatory note. The drug is made anew and its quality is again controlled.

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Introduction

Medicines have been used by humans since prehistoric times. And if earlier people more often resorted to alternative medicine, which includes folk recipes, homeopathy, acupuncture, naturopathy and other methods, then in our time, many people turn to pharmacology, which uses clinically proven medicines.

Thus, over thousands of years, a kind of evolution took place from "grandmother's" recipes to a whole science - pharmaceutical technology, which led to the creation of a large number of drugs. Pharmacy counters are rapidly filling up with more and more new drugs, therefore, there is a need for a more thorough check of the quality of medicines in accordance with the current legislation, as the number of counterfeit drugs has also increased.

The use of low-quality drugs can harm human health and life, even death, since the pharmacological properties of low-quality drugs differ from the properties of the original ones.

About 90% of medicines produced by pharmacies are medicines for medical institutions: hospitals, hospitals, dispensaries. Most of the drugs manufactured for medical institutions are liquid dosage forms (LDF). The quality of their production depends on the life and health of many people. Therefore, the issue of the quality of liquid dosage forms will always be relevant.

That's why the purpose of this work is an analysis of the quality of liquid dosage forms produced by pharmacy No. 418, the only production pharmacy in the Kompressorny microdistrict.

To achieve this goal, it is necessary to solve the following tasks:

To study liquid dosage forms from a theoretical point of view;

Consider methods of intra-pharmacy control (VAK);

Analyze the range of products manufactured by the production department of pharmacy No. 418;

Choose liquid dosage forms for physical, complete chemical and organoleptic analysis (types of intra-pharmacy control available to me);

Conduct a physical, complete chemical and organoleptic analysis of selected liquid dosage forms;

To draw conclusions about the compliance of the quality of the studied liquid dosage forms with the current legislation.

Subject of study: liquid dosage forms produced by pharmacy No. 418.

Object of study: furacilin solution 1/5000 (sterile; for treating wounds), calcium chloride solution 5% (for oral administration), protargol solution 2% (nasal drops).

Research methods: statistical analysis, literature analysis, titration in aqueous media, observation method, refractometry method.

Theoretical part

Liquid dosage forms

Liquid dosage forms- these are comprehensively free disperse systems in which medicinal substances are distributed in a liquid dispersion medium.

2.1. Classification of liquid dosage forms

Liquid dosage forms can be divided into several groups:

By way of application	Composition	Depending on the type of dispersion systems	Depending on the environment
a) for internal use (drops, solutions, mixtures) b) for external use (lotions, rinses, douches, enemas, nasal drops, ear, dental, vaginal, urethral) c) for injections	a) Simple (one-component solutions - from one medicinal substance and solvent) b) Complex (multicomponent - from several medicinal substances and a solvent)	a) True solutions (molecular and ion-dispersion systems less than 1 mmc) b) IUD solutions c) Colloidal IUDs d) Suspensions e) Emulsions f) Combined disperse systems g) Water extracts (infusions, decoctions, mucus)	a) Aqueous solutions b) Non-aqueous solutions

Liquid dosage forms have both advantages and disadvantages.

In any case, for the effective use of medicines, strict adherence to the standard for the preparation of pharmacy products is necessary.

2.2 General technological scheme for the preparation of solutions of mass-volume or volume concentration

The technological scheme for the preparation of solutions includes several stages:

Stage 1 - calculation, verification of doses of substances with doses; calculation of substances and solvent;

Stage 2 - preparation for work;

stage 3 - dissolution;

Stage 4 - purification (filtration of the solution);

Stage 5 - packaging and capping;

stage 6 - registration;

Stage 7 - quality control.

At each stage of the preparation of liquid dosage forms, compliance with the requirements of intra-pharmacy control is mandatory.

2.3. Pharmacy control

Intra-pharmacy quality control of medicines is regulated by the order approved by the Ministry of Health of the Russian Federation No. 751n of 2015. This order applies to all pharmacies on the territory of the Russian Federation, regardless of ownership and departmental affiliation.

Work on quality control of medicines is assigned to the pharmacist and pharmacist-technologist, who are required to own all types of intra-pharmacy control.

Intra-pharmacy control includes all stages of the drug preparation process.

Directions for the implementation of intra-pharmacy control

1. Quality control of medicinal substances (PM) and other items used in the preparation of medicines: A) Compliance with the rules for the reception and storage of medicinal substances in a pharmacy; B) Proper processing of pharmacy utensils and auxiliary materials; C) Compliance with sanitary and pharmaceutical regimes, proper receipt and storage of purified water, concentrates and semi-finished products.

2. Quality control of manufactured medicines: A) Compliance with the rules for taking prescriptions and manufacturing technology of medicines; B) Carrying out all types of intra-pharmacy control

Mandatory types of intra-pharmacy control: written, organoleptic and control on vacation.

Written control provides for the filling of a written control passport in the manufacture of a dosage form. The passport indicates the date, prescription number, the name of the medicinal product in Latin, its quantity, the mass of individual doses and their number, calculation formulas, the necessary coefficients for the calculation, the signature of the person who manufactured the medicinal product, packaged, checked. All calculations are carried out before production and are recorded on the reverse side of the written control passport. The name of medicinal products and their quantities are listed in the written control passport in accordance with the manufacturing technology immediately after manufacturing from memory. The written control passport is stored in the pharmacy for 2 months. In the manufacture of concentrates, semi-finished products, intra-pharmaceutical preparations and packaging of medicines, entries are made not in the passport, but in the registers of laboratory and packaging work.

Organoleptic control consists in checking the appearance of dosage forms, color, smell, uniformity of mixing, absence of mechanical impurities. The control results are recorded in the appropriate journal.

Vacation control includes verification of compliance: packaging of medicinal products with the properties of their constituent medicinal substances; registration of medicinal products - the requirements of regulatory documents; doses of drugs with normalized doses - the age of the patient; numbers on the prescription-number on the label; surnames on the receipt and label-surnames on the prescription; prescription copies; correct labeling. The person dispensing the medicine signs on the back of the prescription.

Selective types of intra-pharmacy control: interrogatory, physical and chemical.

Poll control is used selectively after the pharmacist makes no more than 5 dosage forms. When carrying out this type of control, the pharmacist-technologist names the name of the first ingredient included in the prescription (in complex dosage forms) and its quantity, after which the pharmacist from memory names all the medicines taken and their quantity (when using semi-finished products, he names their composition and concentration).

Physical control is carried out to check the total mass or volume of the medicinal product, the number and mass of individual doses (at least 3 doses) and the quality of the closure of all dosage forms.

Mandatory physical control is subject to:

Each package and intra-pharmacy preparation (at least 3 packages) of injection solutions, eye drops, medicines for newborns and children of the first year of life, sterile dosage forms for external use;

Each series of sterile dosage forms (at least 5 bottles, after packaging before their sterilization): injection solutions, eye drops, dosage forms for newborns and children of the first year of life, sterile dosage forms for external use;

Dosage forms with narcotic, psychotropic and potent substances;

Suppositories (solid at room temperature and melting (dissolving or disintegrating) at body temperature dosage forms).

Medicines are subjected to chemical control depending on the composition, purpose and type of dosage form.

Chemical control consists in assessing the quality of the manufactured medicinal product according to the following indicators: “authenticity”, “test for purity and permissible limits of impurities” (qualitative analysis) and “quantitative determination” (quantitative analysis) of the medicinal substances that make up its composition.

Qualitative analysis is subject to mandatory:

Purified water, water for injection (daily) for the absence of chlorides, sulfates, calcium and magnesium salts. Water for injection additionally for the absence of reducing substances, carbon dioxide and the content of ammonium salts. Quarterly purified water is sent to the control and testing laboratory for a complete chemical analysis;

All medicines coming from the storage rooms to the assistant, and in case of doubt: to the pharmacy, from the warehouse;

Concentrates and semi-finished products;

Medicinal products of industrial production, packaged in a pharmacy (each series);

Medicinal products received by the pharmacy - in case of doubt about their quality;

Homeopathic medicines in the form of an intra-pharmacy blank

and selectively: dosage forms manufactured according to individual prescriptions and requirements of medical institutions (at least 10% of the total number of manufactured drugs). Particular attention is paid to dosage forms for children, eye, as well as medicines containing poisonous and narcotic substances.

Qualitative and quantitative analysis (complete chemical analysis) is necessarily used for quality control:

All injection solutions prior to their sterilization, including the determination of the pH value, isotonizing (that is, substances whose osmotic pressure of solutions is equal to the osmotic pressure of blood plasma) and stabilizing substances. Solutions for injection after sterilization are checked for pH value, authenticity and quantitative content of active substances;

Sterile solutions for external use (for example, solutions for the treatment of open wounds);

Eye drops and ointments with poisonous and narcotic substances;

Dosage forms for newborns;

Solutions of hydrochloric acid (for internal use); solutions of atropine sulfate and silver nitrate;

Concentrates, semi-finished products, triturations (dry mixtures of toxic and potent substances with indifferent substances in a certain (1/10, 1/100) ratio), intra-pharmaceutical preparation (each series);

Stabilizers used in the manufacture of solutions for injections and buffer solutions necessary in the manufacture of eye drops;

The concentration of ethyl alcohol when diluted in a pharmacy;

Ethyl alcohol, in case of doubt in the concentration upon admission to the pharmacy;

Homeopathic granules for disintegration;

Injectable homeopathic solutions.

Medicines made according to individual prescriptions are subject to chemical control selectively, but at least 3 times per shift. Particular attention is paid to dosage forms for children, ophthalmic dosage forms, narcotic and poisonous, solutions for therapeutic enemas. The results of a complete chemical control are recorded in the appropriate journal.

In the process of making solutions for injections, they are subjected to primary and secondary control. The primary control consists in carrying out a complete chemical control (including the determination of pH and ) after filtering and packaging the solution. Secondary control is carried out before packaging after sterilization. It consists in complete chemical control, control for the absence of mechanical impurities, control for sterility and pyrogenic substances (products of vital activity and decay of microorganisms), in checking the quality of vials capping and their filling volume.

The assessment of the quality of manufactured medicines is carried out according to two indicators: “satisfies” (suitable products) and “does not satisfy” (marriage).

After carrying out a complete chemical quality control of medicines, a pharmacist-analyst (a specialist with a higher pharmaceutical education working in the field of medicine production) affixes the analysis number and his signature on the written control passport and on the back of the prescription.

From all of the above, we can conclude that the methods of intra-pharmacy control available to me are: physical, organoleptic and complete chemical analysis.

3. Research part

For the practical part of the study, a pharmacy was chosen within walking distance from the place of residence and education in the Kompressorny microdistrict.

1. Analysis of the produced assortment

I conducted an analysis of the manufactured assortment of the production department of pharmacy No. 418 for the month (from August 20, 2017 to September 20, 2017), based on the information provided by the person acting as head of the pharmacy.

Analysis of the manufactured assortment of the production department of pharmacy No. 418 for the period from August 20, 2017 to September 20, 2017:

Liquid dosage forms 6571(90.4%)

Sterile 4934(67.9%)Non-sterile 1637(22.5%)

1. Injectable 1903(26.2%) 1. External 1568(21.6%)

(including water for injection 720(9.9%))

2. External sterile 1784(24.6%) 2. Internal 69(0.9%)

3. Sterile packaging 852(11.7%)

4. Eye drops 395(5.4%)

Ointments 501(6.9%) (including packaging 173(2.4%))

Powders 194(2.7%) (including packaging152(2.0%))

From the above statistics, we can conclude that liquid dosage forms predominate in the range of manufactured products.

1. Selection of liquid dosage forms for analysis

I opted for the following liquid dosage forms, which were available to me without a prescription:

Furacilin solution 1/5000(sterile; for wound care)

Manufacturing feature: A solution of furacilin is made in a boiling 0.9% (isotonic) solution of sodium chloride, since furacilin is a poorly soluble substance in water.

Also, this solution is produced in large quantities for medical institutions for the treatment of wounds.

Calcium chloride solution 5%(for oral administration)

Manufacturing feature: The substance calcium chloride is very hygroscopic, that is, it easily absorbs moisture from the air and melts very quickly. Therefore, in pharmacies, concentrated solutions are prepared from this substance, more often 1/50. And dosage forms are already made from this concentrated solution.

This solution is widely used in medical institutions and the population.

Protargol solution 2%(nasal drops)

Manufacturing feature: Protargol is poured onto the surface of the water and left alone until completely dissolved (about 30-45 minutes). It is impossible to shake the solution, since when shaking, foam is formed, which envelops the particles of protargol and significantly slows down the dissolution process.

It is widely used in pediatrics for the treatment of inflammation of the nasal mucosa.

Each of these drugs has a peculiarity in the manufacture and wide application in medicine. Based on these factors, I chose the above medicines for analysis.

1. Analysis of liquid dosage form No. 1

Solution of furatsilina 0.02% (1/5000) - 400 ml

Organoleptic control

Index	Requirement	Indicators of the manufactured LF
Appearance of LF	Clear, yellowish-colored solution	Corresponds
	Without smell	Corresponds
No mechanical inclusions		Corresponds

• Physical control

AND ABOUT. (deviation interval) = ±1% (see annex 1)

A.I. = 400 ml. (±1%) / 100% = ±4 ml

D.I.O. (permissible deviation interval) =396 ÷ 404 ml

V measured = 401 ml (Included in the tolerance range)

Complete chemical analysis

Since the analyzed solution of furacilin is prepared in an isotonic solution of sodium chloride, a complete chemical analysis checks not only the presence and content of furacilin, but also the presence and content of sodium chloride too.

Qualitative Analysis

Furacilin: method of observation.

The method is based on the property of furacilin to fluoresce green in ultraviolet radiation.

Sodium chloride:

For chloride ion:

1 ml is added to 3 drops of the solution. purified water, 5-6 drops of HNO 3 (razb.) and 2-3 drops of AgNO 3 form a white cheesy precipitate.

NaCl + AgNO 3 → AgCl ↓ (white curd precipitate) + NaNO 3

To the sodium cation: using a microcrystalline reaction.

The sodium cation, reacting with 2,4,6-tinitrophenol (picric acid), forms yellow needle-like crystals of sodium picrate, emerging from one point.

O 2 N NO 2 O 2 N NO 2

NaCl + → HCl +

Quantitative analysis.

Furacilin:

Furacilin formula:

O 2 N O CH \u003d N - NH - C - NH 2

5-nitrofurfural semicarbazone

iodometry method

The method is based on the reducing properties of the drug due to the hydrazide group.

Methodology: To 2 ml. solution of furatsilina add an excess of 0.01 m iodine solution (2 ml.) and a solution of sodium hydroxide 10% dropwise until discoloration. Then dilute sulfuric acid (2 ml; for an acidic medium) is added and left in a dark place for some time (approximately 2-5 minutes). The released iodine is titrated with 0.01 m sodium thiosulfate solution until it becomes colorless. Indicator - starch (add 3 drops at the end of the titration).

Several reactions take place in parallel:

1. I 2 + 2NaOH → NaI + NaIO + H 2 O (iodine solution in an alkaline medium forms hypoiodite (NaIO)).

O + 2I 2 + 6NaOH → O +

O 2 N O CH \u003d N - NH - C - NH 2 O 2 N O C - H

n (C 6 H 6N4 O 4) \u003d 1 mol z (I 2) \u003d 2 * 2 \u003d 4 (z (I 2) \u003d n (I 2) * N atoms. (I))

N 2 + NH 3 + 4NaI + Na 2 CO 3 + 3H 2 O (nitrofural oxidation to 5-nitrofurfural)

3. NaI + NaIO + H 2 SO 4 → I 2 + Na 2 SO 4 + H 2 O (solution acidification)

4. I 2 + 2Na 2S2 O 3 → 2NaI + Na 2S4 O 6 (titration of the released excess iodine with sodium thiosulfate using an indicator - starch, which is added at the end of the titration)

The titer of sodium thiosulfate according to furacilin is:

M 1/z (molar mass of titrant equivalent)

M (C 6 H 6N4 O 4) \u003d 198.14 g / mol (table value; see Appendix 2)

M 1 / z \u003d \u003d 49.54 g / mol

C 1 / z = 0.01 mol / l (molar concentration of titrant equivalent)

T (C 6 H 6N4 O 4) \u003d 0.0004954 g / ml

ω(C 6 H 6N4 O 4) =

V 0.01 (I 2) \u003d 2 ml (total excess iodine)

V 0.01 (Na 2S2 O 3) \u003d 1.2 ml (volume of titrant spent on titration)

ω (C 6 H 6N4 O 4) = = 0.079264 g

AND ABOUT. (deviation interval) = ±15% (see appendix 1)

MA = 0.08 g (±15%) / 100% = ±0.012 g

D.I.O. (permissible deviation interval) = 0.068 ÷ 0.092 g

ω (C 6 H 6N4 O 4) \u003d 0.079264 g (included in the allowable deviation interval)

Sodium chloride:Mohr's method of argentometry

The method is based on the precipitation of chloride ions with silver cations.

Methodology: 2 ml of water, 2 drops of potassium chromate are added to 0.5 ml of the solution and titrated with 0.1 mol/l solution of silver nitrate until the precipitate turns orange-yellow.

NaCl + AgNO 3 → AgCl↓+ NaNO 3

n(C6H6N4O4) = 1 mol z (I2) = 1 * 1 = 1 (z (AgCl) = Valence (Ag) * N atoms. (Ag))

2AgNO 3 + K 2 CrO4 → Ag 2 CrO 4 ↓ + 2KNO 3

The titer of sodium chloride on silver nitrate is:

M(NaCl) = 58.44 g/mol (table value; see Appendix 2)

M 1 / z \u003d \u003d 58.44 g / mol

T(NaCl) = = 0.005844 g/ml

V 0.1 (AgNO 3) \u003d 0.8 ml (volume of titrant spent on titration)

V lf. = 400 ml (total dosage form volume)

K p. \u003d 1 (indicated on the packaging of the titrant)

a = 0.5 ml (volume of working solution taken for titration)

ω(NaCl) = = 3.74016 g

MA = 3.6 g (±4%) / 100% = ±0.144 g

D.I.O. (permissible deviation interval) = 3.456 ÷ 3.744 g

ω(NaCl) = 3.74016 g (included in the allowable deviation interval)

1. Analysis of liquid dosage form No. 2

Calcium chloride solution 5% - 100 ml

Organoleptic control

Index	Requirement	Indicators of the manufactured LF
Appearance of LF	Clear, colorless solution	Corresponds
	Without smell	Corresponds
No mechanical inclusions	There are no mechanical inclusions	Corresponds

Physical control

AND ABOUT. (deviation interval) = ±3% (see appendix 1)

A.I. = 100 ml. (±3%) / 100% = ±3 ml

D.I.O. (permissible deviation interval) =97 ÷ 103 ml

V measured = 102 ml (Included in the tolerance range)

Also, as part of physical control, it is checked

the quality of the capping of the medicinal product.

Complete chemical analysis

Qualitative Analysis

For chloride ion:

Precipitation of chloride ions by silver cations.

To 0.5 ml of the analyzed solution add 5-6 drops of HCl (razb.) (to acidify the medium) and 2-3 drops of AgNO 3 form a white cheesy precipitate.

CaCl 2 + 2AgNO 3 → 2AgCl ↓ (white curd precipitate) + Ca(NO 3) 2

For calcium cation:

To 0.5 ml of the test solution add 3 drops of ammonium oxalate. A white precipitate forms.

CaCl 2 + (NH 4) 2 C 2 O 4 → CaC 2 O 4 ↓ (white precipitate) + 2NH 4 Cl

Quantitative analysis.

Calcium chloride: refractometry method(since calcium chloride concentration ≥5%)

The refractive index of the analyzed solution (n) is determined at 20˚С. The concentration of CaCl 2 (X, in grams) is calculated by the formula:

X= (At 20˚C)

n 0 \u003d 1.333 (refractive index of light in water; taken from a refractometer)

n \u003d 1.339 (Refractive index of light in the CaCl 2 medium; taken from the refractometer)

V lf. = 100 ml (total dosage form volume)

F = 0.0012 (refractive factor CaCl 2 5%; tabular value, see appendix 3)

AND ABOUT. (deviation interval) = ±4% (see appendix 1)

MA = 5 g (±4%) / 100% = ±0.2 g

D.I.O. (permissible deviation interval) = 4.8 ÷ 5.2 g

X = 5.0 g (Included in the tolerance range)

Conclusion - this liquid dosage form meets the requirements of the order of the Ministry of Health of the Russian Federation dated 10.26.15. No. 751n.

1. Analysis of liquid dosage form No. 3

Protargol solution 2% - 10 ml

Organoleptic control

Index	Requirement	Indicators of the manufactured LF
Appearance of LF	Clear dark brown solution	Corresponds
	Without smell	Corresponds
No mechanical inclusions	There are no mechanical inclusions	Corresponds

• Physical control

AI = 10 ml. (±10%) / 100% = ±1 ml

D.I.O. (permissible deviation interval) = 9 ÷ 11 ml

V measured = 10 ml (Included in the tolerance range)

Also, as part of physical control, it is checked

the quality of the capping of the medicinal product.

Complete chemical analysis

Qualitative Analysis

per silver cation

Precipitation of silver cations by chloride ions.

To 0.5 ml of the test solution add 3 drops of nitric acid and heat. The liquid turns yellow, turbidity appears. Then 2 drops of hydrochloric acid are added, a yellowish-white cheesy precipitate is formed.

LS HNO3, t0 Ag +

HCl + Ag + → AgCl↓ + H +

For protein:

When heated, the protein in the analyzed solution is carbonized. There is a smell of burnt horn.

The analyzed solution is heated to charring of the protein, the smell of burnt horn is felt.

Quantitative Analysis

For silver: rhodanometry method (Folhard argentometry), direct titration method.

In pure protargol, silver is only 8%, the rest is protein. Therefore, the titer of protargol is considered through the conditional titer of silver. Protein is not quantified.

The method is based on the precipitation of silver cations by rhodanide ions.

3 drops of nitric acid (to acidify the medium) and 3 drops of ferric ammonium alum are added to 2 ml of the preparation, heated to discoloration, and the discolored solution is titrated with 0.1 m ammonium thiocyanate solution to a pinkish-red color.

Ag + + NH 4 SCN → AgSCN↓ + NH 4 +

n(Ag) \u003d 1 mol z (NH 4 SCN) \u003d 1 * 1 \u003d 1 (z (NH 4 SCN) \u003d Valence (NH 4) * N groups (NH 4))

3 NH 4 SCN + Fe 3+ → Fe(SCN) 3 + 3 NH 4 +

Silver titer for ammonium thiocyanate is:

M 1/z (molar mass equivalent)

M(Ag) = 107.9 g/mol (table value; see Appendix 2)

M 1 / z \u003d \u003d 107.9 g / mol

C 1 / z \u003d 0.1 mol / l (molar equivalent concentration)

T(Ag) = 0.01079 g/ml

T protargol conditional = = = 0.134875 g / ml

The mass fraction of silver in the analyzed solution in grams is equal to:

V 0.1 (NH 4 SCN) \u003d 0.3 ml (volume of titrant spent on titration)

V lf. = 10 ml (total dosage form volume)

K p. \u003d 1 (indicated on the packaging of the titrant)

a = 2 ml (volume of working solution taken for titration)

ω(Ag) = = 0.2023125 g

AND ABOUT. (deviation interval) = ±10% (see appendix 1)

AI \u003d 0.2g. (±10%) / 100% = ±0.02g

D.I.O. (permissible deviation interval) = 0.18 ÷ 0.22 g

ω(Ag) = 0.2023125 g (included in the allowable deviation interval)

Conclusion - this liquid dosage form meets the requirements of the order of the Ministry of Health of the Russian Federation dated 10.26.15. No. 751n.

4. Conclusion

1. I studied the classification of liquid dosage forms and the general technology for their manufacture, methods of intra-pharmacy control and found out which of them I can carry out.

2. In the experimental part, I analyzed the range of products manufactured by the production department of pharmacy No. 418. From the analysis, we can conclude that the vast majority of liquid dosage forms are produced - more than 90%, so the topic of my research work, where I consider only liquid dosage forms, is very relevant.

She also selected and analyzed liquid dosage forms and made conclusions about their quality compliance with the current legislation. I believe that the tasks set by me were completed.

3. At Pharmacy No. 418, the quality control system for liquid medicines is organized in accordance with the current legislation.

5. List of references

Order of the Ministry of Health of the Russian Federation of October 26, 2015 N 751n “On approval of the rules

manufacturing and dispensing of medicinal products for medical

application by pharmacy organizations, individual entrepreneurs licensed for pharmaceutical activities "

E.V. Ermilova, V.V. Dudko, T.V. Kadyrova "Analysis of complex dosage forms" Tutorial. Ministry of Education. Siberian State Medical University. Tomsk, 2012

Pletneva T.V., Uspenskaya E.V., Muradova L.I. Quality control of medicines. - M.: GEOTAR-Media, 2014. - 555 p.

Krasnyuk I.I., Mikhailova G.V., Muradova L.I. Pharmaceutical technology. Technology of dosage forms. - M.: GEOTAR-Media, 2013. - 560 p.

Internet - resources, electronic tutorials and textbooks:

GUARANTEE URL: http://www.garant.ru

Ministry of Health of the Russian Federation URL : http://www.rosminzdrav.ru/

http://xumuk.ru/

6.Applications

Attachment 1

Permissible deviations in the total volume of LLF in the manufacture of mass-volume method.
Prescribed volume, ml	Deviations, %
Over 10 to 20 Over 20 to 50 Over 50 to 150 Over 150 to 200
Permissible deviations in the weight of the sample of individual medicinal substances in the LDF in the manufacture of the mass-volume method.
Registered weight, g	Deviations, %
Over 0.02 to 0.1 Over 0.1 to 0.2 Over 0.2 to 0.5 Over 0.5 to 0.8 Over 0.8 to 1.0 Over 1.0 to 2.0 Over 2.0 to 5.0

DEVIATIONS PERMISSIBLE IN THE MANUFACTURE OF LIQUID

DOSAGE FORMS IN THE PHARMACY.

Annex 2

Table "MOLAR MASS OF DRUG SUBSTANCES"

	medicinal substance	Molar mass
	Acetylsalicylic acid
	Vitamin C
	Adrenaline hydrotartrate
	Anestezin
	Analgin
	Antipyrine
	Apomorphine hydrochloride
	Atropine sulfate
	Benzoic acid
	Boric acid
	Barbital
	barbital sodium
	Butadion
	Glutamic acid
	Hexamethylenetetramine
	Diphenhydramine
	calcium chloride
	calcium gluconate
	calcium lactate
	Codeine Phosphate
	caffeine anhydrous
	Potassium chloride
	Potassium bromide
	Potassium iodide
	Potassium permanganate
	Levomecithin
	Magnesium sulfate
	Morphine hydrochloride
	sodium benzoate
	Sodium bromide
	Sodium chloride
	sodium iodide
	sodium bicarbonate
	sodium nitrite
	Sodium salicylate
	Sodium tetraborate
	Sodium thiosulfate
	A nicotinic acid
	norsulfazol
	Norsulfazole sodium
	Novocaine
	Papavirine hydrochloride
	Pilocarpine hydrochloride
	Promedol
	Pyridoxine hydrochloride
	Hydrogen peroxide
	Resorcinol
	Riboflavin
	Silver nitrate
	Streptocid soluble
	Sulfacyl sodium
	Sulfadimezin
	Salicylic acid
	Theobromine
	Theophylline
	Thiamine bromide
	Thiamine chloride
	Mercury oxide yellow
	Phenobarbital
	Phenyl salicylate
	Ftalazol
	Furacilin
	Hydrochloric acid
	Quinine dihydrochloride
	Quinine hydrochloride
	Quinine sulfate
	Chloral hydrate
	zinc sulfate
	Ethaminal sodium
	Ethylmorphine hydrochloride
	Ephedrine hydrochloride
	Eufillina: theophylline
	Ethylenediamine

Annex 3

REFRACTIVE INDEX TABLE FOR MEDICINAL SUBSTANCES

Amidopyrine 4%		Analgin
Ammonium bromide 5%		Analgin 20%
Ammonium bromide 20%		Antipyrine 1%
Ammonium chloride 10%		Antipyrine 5%
Ammonium chloride 20%		Atropine sulfate
Barbamil 3%		Barbital
Barbamil 5%		sodium barbital
Urotropin 10%		Glucose (moisture content 10%)
Urotropin 20%		Glucose b/w
Urotropin 40%
Potassium bromide 5%		Diphenhydramine
Potassium bromide 10%		K-ta aminocaproic 5%
Potassium bromide 20%		K-ta ascorbic
Potassium iodide		Boric acid 3%
Potassium chloride 10%		K-ta glutamine
Potassium chloride 5%		K-ta nicotine
calcium gluconate		Acetic acid
calcium lactate		Codeine Phosphate
Calcium chloride 5%		cardiamine
Calcium chloride 20%
Calcium chloride 50%		Caffeine-sodium benzoate
Magnesium sulfate up to 50%		Magnesium chloride
Magnesium sulfate up to 30%		copper sulfate
Valerian tincture		Sodium salicylate 20%
Sodium bromide 5%		Sodium chloride 5%
Sodium bromide 10%		Sodium chloride 10%
Sodium bromide 20%		Sodium tetraborate
sodium benzoate		Sodium thiosulfate 10%
sodium bicarbonate		Sodium thiosulfate 20%
sodium hydrocitrate		Sodium thiosulfate 40%
Sodium iodide 5%		Sodium thiosulfate 50%
Sodium iodide 10%		Sodium thiosulfate 60%
Sodium iodide 30%		sodium citrate
Sodium sulfate		Sodium etaminal
Sodium sulfate b/w		Novacainamide 10%
Sodium salicylate 10%		Novocaine
Pilocarpine hydrochloride
Pachycarpine hydroiodide		Pyridoxine g/h
papaverine hydrochloride		Promedol
		Alcohol ammonia
Sodium sulfate		Streptocide solution
Resorcinol		Quinine g / x
zinc sulfate		Chloral hydrate
Euffilin 10%		Ephedrine g/h