Standardization of medicines is, as a rule, the main guarantor of their high quality in mass production and ensures the effectiveness and safety of use. Quality management is achieved through the implementation of a set of activities, methods and means that ensure and maintain product quality. Standardization solves the following main tasks: development of regulatory requirements for the quality of finished products, as well as for the quality of raw materials and semi-finished products used in their manufacture; development of requirements and standards in the field of design and production of products, methods and means of testing and monitoring; ensuring the unity and accuracy of measurements in the country, developing new and improving existing standards of units of measurement; Pharmacopoeial monograph (FS) - this is a regulatory and technical document that establishes requirements for the quality of a medicinal product or medicinal plant raw materials, its packaging, conditions and shelf life, quality control methods, approved by the authorized federal executive body and having the nature of a state standard. Pharmacopoeial monographs (types): Pharmacopoeial monograph of the enterprise (FSP) - this is a drug quality standard under a trade name, contains a list of methods and indicators for quality control of drugs produced by a specific enterprise, takes into account the specific technology of this enterprise, which has been examined and registered in the prescribed manner in accordance with the State Pharmacopoeia. General pharmacopoeial monograph (GPM):- this is a state standard for the quality of medicines, containing the basic requirements for the dosage form, as well as a description of standard methods for quality control of medicines. The pharmacopoeial monograph, general pharmacopoeial monograph and pharmacopoeial monograph of the enterprise are approved by the head of the Department, and then registered with an organization authorized by the Ministry of Health of the Russian Federation, with the obligatory assignment of a designation. Private Pharmacopoeial monograph (PCS):- this is a regulatory and technical document regulating the quality and safety of a medicinal product; a private pharmacopoeial monograph is created for the medicinal product under an international non-proprietary name. Temporary pharmacopoeial monograph:– this is a regulatory and technical document approved for the period of development of industrial production of a medicinal product and for developing industrial technology of methods for determining the quality or indicators of a new medicinal product for a period of no more than 3 years.

14.The main sections of the FS using the example of a pharmaceutical substance.

Pharmaceutical substance– a standardized biologically active substance or a standardized mixture of biologically active substances, obtained by synthesis methods or using biological, molecular genetic or cellular technologies, intended for the preparation of medicinal products.

Many substances are salts of organic acids and organic bases. The names of pharmacopoeial monographs for such substances must include the name of both the cation and the anion. For example, diclofenac sodium, diclofenac potassium or amlodipine besylate or doxazosin mesylate or ketamine hydrochloride. The names of substances that are esters by their chemical nature are written together. For example, Beclamethasone dipropionate, and not Beclamethasone dipropionate, or Betamethasone valerate, and not Betamethasone valerate.

In the introductory part of the pharmacopoeial monograph, the substance is given its chemical name according to the JUPAC nomenclature, structural formula, empirical formula and relative molecular weight.

Description. Indicates the characteristics of the physical state and color of the substance. No description of taste should be included. Where necessary, information about odor and hygroscopicity is provided.

For solid substances, the indication “crystalline”, “fine crystalline” or “amorphous powder” is required. The crystallinity characteristics of a substance are one of the important parameters on which the quality of solid dosage forms depends.

In some cases, a numerical range of particle size may be specified, and a study of crystal shape may also be introduced. Such tests are placed in separate sections.

Assessment of the polymorphism of a substance is mandatory in cases where the polymorphic modification determines the pharmacological activity of the finished dosage form and its pharmacotechnological properties.

Solubility. To determine solubility, solvents covering a wide range of polarities should be used, for example: water, 96% alcohol, acetone, hexane. The use of low-boiling, flammable (eg diethyl ether) or highly toxic (eg benzene) solvents is not recommended.

Authenticity. To establish the authenticity of a substance, an optimal combination of physicochemical and chemical methods is recommended - infrared spectroscopy, absorption spectrophotometry, thin-layer, gas and high-performance liquid chromatography (TLC, GC and HPLC) and qualitative (primarily specific) chemical reactions.

Melting temperature. The test is usually used to characterize solids.

In accordance with Article 7 of the Federal Law of April 12, 2010 No. 61-FZ “On the Circulation of Medicines” (Collected Legislation of the Russian Federation, 2010, No. 16, Art. 1815; No. 31, Art. 4161) I order:

Approve the Procedure for developing general pharmacopoeial monographs and pharmacopoeial monographs and including them in the state pharmacopoeia, as well as posting data on the state pharmacopoeia on the official website on the Internet in accordance with the appendix.

Application

The procedure for developing general pharmacopoeial monographs and pharmacopoeial monographs and including them in the state pharmacopoeia, as well as posting data on the state pharmacopoeia on the official website on the Internet

1. This Procedure establishes the rules for the development, approval of general pharmacopoeial monographs and pharmacopoeial monographs, their inclusion in the state pharmacopoeia and publications of the state pharmacopoeia, as well as the rules and terms for posting data on the state pharmacopoeia and its annexes on the official website on the Internet.

2. The basic concepts in this Procedure are used in the same meaning as in the Federal Law of April 12, 2010 No. 61-FZ “On the Circulation of Medicines”.

3. General pharmacopoeial monographs and pharmacopoeial monographs are developed and revised taking into account new advances in the field of biological, biochemical, microbiological, physicochemical, physical, chemical and other methods of analysis of drugs for medical use.

4. General pharmacopoeial monographs and pharmacopoeial monographs are developed by the Ministry of Health and Social Development of the Russian Federation, including on the basis of proposals received from subjects of medicines circulation.

5. General pharmacopoeial monographs and pharmacopoeial monographs are approved by the Ministry of Health and Social Development of the Russian Federation and constitute the state pharmacopoeia.

6. The development of a pharmacopoeial monograph for an original medicinal product and its inclusion in the state pharmacopoeia during the period of protection of the exclusive right certified by a patent for the original medicinal product is carried out with the consent of its developer.

7. The general pharmacopoeial monograph contains a list of quality indicators and (or) quality control methods for a specific dosage form, medicinal plant raw materials, descriptions of biological, biochemical, microbiological, physicochemical, physical, chemical and other methods of analysis of a medicinal product for medical use, as well as requirements for reagents, titrated solutions, and indicators used for this analysis.

8. The pharmacopoeial monograph contains a list of quality indicators and methods for quality control of a medicinal product for medical use.

The structure and indicators of a pharmacopoeial monograph in each specific case can be individual based on the specific profile and nature of the origin of the drug. A pharmacopoeial monograph is developed for a medicinal product under an international nonproprietary name, if available (for monocomponent medicinal products), and contains a mandatory list of indicators and methods of quality control, taking into account its dosage form.

9. Upon completion of the development of a general pharmacopoeial monograph and a pharmacopoeial monograph, the responsible department of the Ministry of Health and Social Development of the Russian Federation (hereinafter referred to as the Department) publishes the draft article on the official website of the Ministry of Health and Social Development of the Russian Federation on the Internet for public discussion for a period of thirty days .

10. After the established period for public discussion, the Department sends to the Council of the Ministry of Health and Social Development of the Russian Federation for the State Pharmacopoeia (hereinafter referred to as the Council for the State Pharmacopoeia), a draft general pharmacopoeial article and a pharmacopoeial article with a documentary justification containing comprehensive data on the feasibility and necessity of its statements.

11. The State Pharmacopoeia Council is formed from representatives of scientific organizations, educational institutions of higher professional education, representatives of the pharmaceutical industry, as well as representatives of the Department, in order to review general pharmacopoeial monographs and pharmacopoeial monographs for their scientific validity and the need for practical application.

12. The State Pharmacopoeia Council within 30 days reviews the submitted draft general pharmacopoeial monograph and pharmacopoeial monograph and makes a decision on approval of the proposed draft or disapproval of the draft, indicating the reasons.

13. Within five working days after approval of the draft general pharmacopoeial monograph and pharmacopoeial monograph, the Department prepares a draft order of the Ministry of Health and Social Development of the Russian Federation on approval of the general pharmacopoeial monograph and pharmacopoeial monograph.

14. In case of disapproval of the draft general pharmacopoeial monograph and pharmacopoeial monograph, the Department finalizes the draft general pharmacopoeial monograph and pharmacopoeial monograph, taking into account the recommendations of the State Pharmacopoeia Council. The project completion period should not exceed forty days.

15. Approved general pharmacopoeial monographs and pharmacopoeial monographs are included in the state pharmacopoeia, which is published by the Ministry of Health and Social Development of the Russian Federation at least once every five years, during the period between which appendices to the state pharmacopoeia containing general pharmacopoeial monographs and pharmacopoeial monographs are published, approved after the publication or reissue of the state pharmacopoeia.

16. Approved general pharmacopoeial monographs and pharmacopoeial monographs, the state pharmacopoeia and its annexes are published in specialized printed publications and posted within three working days from the date of their approval and publication on the official website of the Ministry of Health and Social Development of the Russian Federation on the Internet.

17. The State Pharmacopoeia is published and posted on the official website of the Ministry of Health and Social Development of the Russian Federation on the Internet by entering the following information:

a) general pharmacopoeial articles included in the next edition of the state pharmacopoeia;

b) pharmacopoeial articles included in the next edition of the state pharmacopoeia;

c) appendices to the state pharmacopoeia, containing general pharmacopoeial monographs and pharmacopoeial monographs approved after the publication or reissue of the state pharmacopoeia.

18. Data from the state pharmacopoeia posted on the official website of the Ministry of Health and Social Development of the Russian Federation on the Internet are open and publicly available.

19. Timely updating of state pharmacopoeia data and implementation of technical measures to protect the information contained in them from unauthorized access is ensured by the Department of Informatization of the Ministry of Health and Social Development of the Russian Federation.

20. Information is updated continuously. A backup copy of the state pharmacopoeia data is formed in order to protect the information contained in it, at least once a day. Protection of state pharmacopoeia data from unauthorized access is carried out by built-in operating system tools and the state pharmacopoeia data management system.

Order of the Ministry of Health and Social Development of the Russian Federation dated August 26, 2010 No. 756n “On approval of the procedure for developing general pharmacopoeial monographs and pharmacopoeial monographs and their inclusion in the state pharmacopoeia, as well as posting data on the state pharmacopoeia on the official website on the Internet”

Document overview

On September 1, 2010, a new law regulating the circulation of medicines came into force.

In this regard, it is determined how pharmacopoeial monographs (including general ones) are developed and included in the state pharmacopoeia.

A pharmacopoeial monograph is a document that lists the indicators and methods for controlling the quality of a medicine. The general article includes indicators and (or) methods for quality control of a specific dosage form, medicinal plant raw materials, descriptions of methods for analyzing the drug, requirements for the reagents used for this, titrated solutions, and indicators.

Articles are developed and approved by the Russian Ministry of Health and Social Development. They are revised to take into account new advances in drug analysis methods.

The draft article is posted on the Ministry’s website for 30 days for public discussion. It is then sent to the State Pharmacopoeia Council, where it is reviewed within 30 days.

The project, which was not approved by the council, is being finalized.

Approved articles are included in the state pharmacopoeia. It is published at least once every 5 years. In between, applications are released.

These articles, the state pharmacopoeia and appendices are published in specialized printed publications and posted on the website of the Ministry of Health and Social Development of Russia.

A pharmacopoeial monograph is a state document reflecting the quality criteria of medicines and raw materials for them. The article discusses the concept of pharmaceutical substances, the levels of their regulation, as well as the types and structure of pharmacopoeial monographs

A pharmacopoeial monograph (PS) is a document reflecting the quality criteria for medicines and materials for them. It also contains information about packaging, terms, storage conditions and quality control methods.

The article discusses the concept of pharmaceutical substances, the levels of their regulation, as well as the types and structure of pharmacopoeial monographs.

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From the article you will learn:

A pharmacopoeial monograph is a normative document of national importance. It is approved by executive authorities and contains indicators of the quality of the drug and methods for its control, and also describes methods for studying the quality of the drug and the requirements for reagents, solutions and indicators.

The name of the raw material for the drug is indicated in the document both in Russian and in Latin, with the latter playing the role of an international name.

Until January 1, 2018, the development of the FS was the responsibility of the Ministry of Health. Since the beginning of this year, these powers have been transferred to expert organizations.

Pharmacopoeia: levels of regulation

Pharmacopoeia is a collection of requirements for the quality of medicines. The history of such documents dates back to ancient times. Among the first of these are the Edwin Smith papyrus, the pharmacopoeia of Pliny the Elder, the Garden of Health by Peter Schöffel, and the pharmacopoeia compiled during the Renaissance in Italy. The first pharmacopoeia, under the supervision of government authorities, was published in the mid-16th century in Germany.

In Russia, the first pharmacopoeia was published in Latin in the 18th century, and in Russian in the 19th century. In fact, the serial numbering of the FS began with a document published in the 19th century (the 11th edition was published at the end of the last century).

The FS regulates the quality requirements for the active substances of drugs, auxiliary components, diagnostic tools and products prepared from them. Its provisions are based on the achievements of pharmaceutical analysis and pharmaceutical chemistry, their criteria, methods and methods.

The technologies for preparing and quality control of a particular medicine, the maximum dosages of drugs, are prescribed here. Strict adherence to the requirements set out in the FS in combination with compliance with the GMP standard is the key to the high quality of the received medicines and substances.

1. State pharmacopoeial monograph is a legislative document at the state level, under government supervision; its provisions and norms are mandatory for all enterprises and industries whose activities are related to the production, storage and use of medicines (including those based on medicinal plants).
2. Pharmacopoeial monograph of an enterprise (FSP) is a document that includes a list of criteria and methods for quality control of a drug produced by a specific enterprise, taking into account the technologies used, examination and registration procedures (the maximum period of validity of the FSP is 5 years).
3. General pharmacopoeial monograph (GPM) - includes the basic requirements for the form of the drug and standard methods for assessing its quality, as well as a list of norms and examination methods for a specific drug form;
4. A private pharmacopoeial monograph (PPM) is a regulatory and technical regulation for the safety and quality of a medicinal product, developed for a drug under the INN recommended by WHO.
5. Temporary pharmacopoeial monograph - is being developed for the period of development of industrial production of the drug and to improve the industrial technology of methods for assessing its properties and quality (valid for 3 years).

FS are periodically revised taking into account advances in the field of chemistry, pharmaceuticals, medicine and other scientific disciplines. The structure and criteria of the FS in each individual case may vary based on the specific profile and origin of the drug and its raw materials.

The Pharmacopoeia contains:

• description of drug analysis methods;
• data on indicators, solutions and reagents used to assess the quality of the drug;
• description of articles on certain substances and substances;
• lists of toxic and potent ingredients;
• lists of dosages for people of different ages.

National pharmacopoeias

Pharmacopoeial monographs are available in many countries of the world - in the USA, France, Great Britain, Belarus, Ukraine, Germany, etc. WHO is developing an International Pharmacopoeial monograph, but it does not have the properties of a law, which cannot be said about national pharmacopoeias.

An international or European pharmacopoeial monograph is used as a regulatory document only in those states that do not develop their own similar documents. In addition, many pharmaceutical giants produce medicines according to the requirements of the customer company, that is, either on the basis of one or another pharmaceutical substance.

Structure of a pharmacopoeial monograph

The FS contains a lot of valuable information located in the appropriate sections.

They are presented in the table below:

Introduction (preamble)	Time of collection of raw materials (calendar or growing season) Characteristics of raw materials by processing mode: freshly harvested, dried, fresh frozen, threshed; wild, cultivated; life form of a plant; name of the producing plant and family (indicated in Russian and Latin)
External signs	Composition of raw materials Size of raw materials Characteristic diagnostic signs Smell and taste (for non-toxic varieties)
Microscopy	Diagnostic signs of the anatomy of raw materials (fluorescent microscopy is used for some species) Type of microspecimen on which the study is carried out
Qualitative reactions	Qualitative and histochemical reactions Chromatographic authenticity tests for the main groups of active substances, methods for their implementation and results
Numerical indicators	Specific criteria and their standards for whole, cut raw materials or raw materials in powder form Degree of grinding Concentration of active or extractive substances, impurities, total ash and ash insoluble in hydrochloric acid solution
Qualitative definition	A method for quantitative determination of the main active ingredients in the form of a sum, in terms of any substance contained in a given raw material (if an individual substance is isolated, the content of this particular component in the raw material is standardized)
Package	Types of packaging Weight of raw materials per packaging unit
Microbiological purity	Methods for detecting microorganisms Acceptable limits of microorganisms
Marking	Provided in accordance with the requirements for graphic design of drugs
Transportation	Requirements for transportation, loading and unloading of drugs, handling them after transportation
Storage	Storage conditions for drugs Measures to protect against the influence of adverse factors
Best before date	Time period in which raw materials can be used
pharmachologic effect	Pharmacological group, which includes specific raw materials

33.What is the State Pharmacopoeia, general and private pharmacopoeial articles.

Pharmacopoeia(from the other gr. φαρμακον - medicine, poison, and other gr. ποιη - I make, I manufacture) - a collection of official documents (a set of standards and regulations) establishing quality standards for medicinal raw materials - medical substances, excipients, diagnostic and medicinal products and preparations made from them.

The provisions of the pharmacopoeia are based on the achievements of pharmaceutical chemistry and its pharmaceutical analysis, its criteria, methods and methods. This document includes instructions for the manufacture and quality control of drugs. Determines the highest doses of drugs and establishes requirements for medicinal raw materials. Compliance with the stated standards and requirements of the Pharmacopoeia in combination with compliance with the requirements of the GMP standard ensures the proper quality of medicinal substances and preparations.

State Pharmacopoeia - pharmacopoeia under state supervision. The State Pharmacopoeia is a document of national legislative force; its requirements are mandatory for all organizations of a given state involved in the manufacture, storage and use of medicines, including herbal ones.

It contains:

descriptions of methods of chemical, physicochemical and biological analyzes of medicines,

information about the reagents and indicators required for this,

descriptions of articles on individual medicinal substances and medicinal products,

lists of poisonous (list A) and potent (list B) drugs,

tables of highest single and daily doses for adults and children.

The first Pharmacopoeia of Russia (“Pharmacopoea Rossica”) was published in 1778.

In subsequent years, the following editions of the Pharmacopoeia were published in Russian: the second in 1871, the third - 1880, the fourth - 1891, the fifth - 1902, the sixth - 1910, the seventh - 1925, the eighth - 1946, the ninth - 1961, the tenth - 1968, the eleventh - 1987 (first issue) and 1990 - (second issue).

Part 1 of the “State Pharmacopoeia of the Russian Federation XII edition” was released in February 2008, and has been put into effect since 2009. Now work continues on the release of the second part.

The compilation, addition and republication of the Pharmacopoeia was previously carried out by the Pharmacopoeia Committee. Currently, the Pharmacopoeia is being prepared by an editorial board, which includes representatives of the Ministry of Health and Social Development, Roszdravnadzor, Roszdrav, FFOMS and leading Russian scientists.

Pharmacopoeial monograph (FS)- this is a regulatory and technical document that establishes requirements for the quality of a medicinal product or medicinal plant raw materials, its packaging, conditions and shelf life, quality control methods, approved by the authorized federal executive body and having the nature of a state standard.

The pharmacopoeial monograph contains: the name of the medicinal plant raw material in both Russian and Latin (in this case, the Latin name of the medicinal raw material serves as an international name)

Pharmacopoeial monographs (types):

Pharmacopoeial monograph of the enterprise (FSP):

This is a quality standard for a medicinal product under a trade name, contains a list of methods and indicators for quality control of a medicinal product produced by a specific enterprise, takes into account the specific technology of this enterprise, which has been examined and registered in the prescribed manner in accordance with the State Pharmacopoeia, pharmacopoeial articles of these standards, and these quality indicators , must not be lower than the requirements found in the State Pharmacopoeia.

The validity period of a pharmacopoeial article (pharmaceutical article) of an enterprise is established upon its approval for no more than 5 years, taking into account the level of the technological process of a specific production of a medicinal product.

General pharmacopoeial monograph (GPM):

This is a state standard for the quality of medicinal products, containing the basic requirements for the dosage form, as well as a description of standard methods for quality control of medicinal products. The general pharmacopoeial article includes: a list of standardized indicators and test methods for a specific dosage form, a description of chemical, physical, physicochemical, biological, biochemical, microbiological methods for analyzing drugs, this also includes requirements for the titrated solutions, reagents, and indicators used.

The pharmacopoeial monograph, general pharmacopoeial monograph and pharmacopoeial monograph of the enterprise are approved by the head of the Department, and then registered with an organization authorized by the Ministry of Health of the Russian Federation, with the obligatory assignment of a designation.

Private pharmacopoeial monograph (PPS):

This is a regulatory and technical document regulating the quality and safety of a medicinal product; a private pharmacopoeial monograph is created for the medicinal product under an international nonproprietary name (if it exists, or under a name that replaces it in a mandatory established manner; this also includes a list of standardized indicators and methods testing of this drug, as well as links to general pharmacopoeial monographs.

Temporary pharmacopoeial monograph:

– this is a regulatory and technical document approved for the period of development of industrial production of a medicinal product and for developing industrial technology of methods for determining the quality or indicators of a new medicinal product for a period of no more than 3 years.

Structure of a pharmacopoeial monograph:

Introductory part. The introductory part (preamble) states:

The time of collection of raw materials (vegetation phase, sometimes a calendar period) and the characteristics of the raw materials according to the mode of their technological processing are necessarily given:

Dried, threshed, freshly harvested, freshly frozen, etc.;

Wild or cultivated plant;

His life form;

Name of the producing plant and family in Russian and Latin.

External signs. The most important indicator of the authenticity and purity of raw materials. This section states:

Composition of raw materials;

Characteristic diagnostic signs, characteristic smell and taste (for non-poisonous species), dimensions of raw materials.

Microscopy. The most important method for determining the authenticity of medicinal raw materials. Section contains:

Diagnostic signs of the anatomical structure of raw materials (fluorescent microscopy is provided for some species);

Type of microslide on which the study is carried out.

Qualitative reactions. The section provides the actual qualitative, histochemical reactions, or chromatographic authenticity tests, for the main groups of active substances, the methodology for their implementation and the results.

Numerical indicators. The section includes specific indicators and their standards:

For whole, cut or powdered raw materials, which are the standard for all types of medicinal plant raw materials and determine its quality;

Quantitation. A method is given for the quantitative determination of the main active substances in the form of total content, in terms of any substance contained in a given raw material. If an individual substance is isolated (for example, platiphylline, etc.), the content of this particular component in the raw material is normalized. If the method of quantitative analysis is set out in the SP XI issue I, then a link to it is provided in the private pharmacopoeial monograph.

Package. The types of packaging and the mass of raw materials per packaging unit are indicated.

Microbiological purity. Method for determining microorganisms and their permissible limits.

Marking. Provided in accordance with the requirements for graphic design of medicines.

Transportation. If necessary, requirements for loading, unloading of products, and handling after transportation are indicated.

Storage. The storage conditions for products are indicated, including requirements for protecting products from the influence of climatic factors.

Best before date. The time during which medicinal raw materials can be used.

Pharmachologic effect. Pharmacological group to which medicinal raw materials are assigned.

34. Basics for ointments, classification and characteristics

Ointment This is a soft dosage form intended for application to the skin, wounds, mucous membranes, consisting of an ointment base and medicinal substances distributed in it.

Requirements for ointments:

1.must have a soft consistency, ensuring ease of application to the skin and mucous membranes

2.maximum dispersion of the leukin and their uniform distribution throughout the ointment (uniformity)

3.storage stability

4.absence of mechanical inclusions

5.should not change its composition during storage and use

6.should not delaminate during storage

7.should not be toxic or allergenic to the skin

8. for eye ointments, for introduction into the body cavity, for newborns, with antibiotics - sterility

9.absence of negative interactions between drugs and excipients

The ointment contains:

1. ointment base (lanolin, petroleum jelly)

2. lek. Ingredients (zinc oxide, sulfur, dermatol, novocaine, protargol, anesthesin, menthol, camphor, furatsilin, sulfacylamides)

Classification of ointments:

1. composition: a) simple

B) complex

2. by the nature of the action:

A) superficial

B) deep

3.at destination:

A) ocular

B) for the nose, etc.

4.consistency:

A) liniment (medicinal form for external use, which is a thick, liquid or gelatinous mass that dissolves at body temperature. From a physicochemical point of view, it is a dispersion system with varying degrees of dispersion and homogeneity)

B) paste (ointments with a powder percentage of 25 or more, suspension and combined types, more difficult to spread, but last longer and stay on the skin)

5.by type of disperse system:

A) homogeneous (single-phase) ointments-alloys (a combination of mutually soluble fusible components), ointment solutions (formed by substances soluble in the base - if the base is petroleum jelly, then homogeneous ointments are formed by: camphor, menthol, phenol), extraction (obtained by extraction with oils raw materials of plant/animal origin))

B) heterogeneous (two-phase) ointments-suspensions (the main task in preparation is to grind the solid substance as finely as possible), ointments-emulsions (containing drugs, soluble in water, but insoluble in the base (protargol, novocaine, collargol, ephedrine hydrochloride), aqueous solutions of drugs and pharmacopoeial liquids (Adrenaline solution, liquid Burov), viscous liquids (ichthyol, tar), combined (contain substances that form different types of ointments, but such an ointment is prepared in one mortar!) )

Most often, combination ointments are prepared in pharmacies.

Concept and characteristics of pharmacopoeia. Structure of a pharmacopoeial monograph. GP quality control requirements. Main types of standard samples. History of domestic pharmacopoeias. State Pharmacopoeia X and XI. Pharmacopoeia of the Russian Federation and the USA.

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Chapter 1. Concept and characteristics of pharmacopoeia

1.1 Definition of pharmacopoeia

The State Pharmacopoeia is the main document regulating pharmaceutical analysis.

Pharmacopoeia (pharmakopiea)- a Greek word containing two roots: Pharmakon- medicine and poieo- I do (the art of preparing medicines).

Pharmacopoeia- this is an official guide for pharmacists (pharmacists), containing a description of the properties, authentication and quality testing, and storage conditions.

The Pharmacopoeia contains mandatory national standards and regulations that regulate the quality of medicines.

The GF consists of general pharmacopoeial monographs (GPM) and pharmacopoeial monographs (FS).

General pharmacopoeial monograph- This is the State Quality Standard for Medicines, containing the basic requirements for the dosage form and/or a description of standard methods for quality control of medicines. The General Pharmacopoeia Monograph includes a list of standardized indicators or test methods for a specific dosage form, a description of physical, physicochemical, chemical, biochemical, biological, microbiological methods for analyzing drugs, requirements for the reagents used, titrated solutions, and indicators.

Pharmacopoeial monograph- this is the State quality standard for drugs under the international nonproprietary name (INN), which is given by the World Health Organization (WHO) for single-component drugs (if available), containing a mandatory list of indicators and methods of quality control (taking into account its dosage form) that meet the requirements of leading foreign pharmacopoeias.

General pharmacopoeial monographs and pharmacopoeial monographs must be revised by the Scientific Center for Expertise and State Control of Medicines of the Russian Ministry of Health at least every five years.

Pharmacopoeial monograph of the enterprise- a quality standard for a medicinal product under a trade name, containing a list of indicators and methods for quality control of drugs produced by a specific enterprise, taking into account the specific technology of this enterprise, and has been examined and registered in the prescribed manner.

1.2 Structure of a pharmacopoeial monograph

The structure of a pharmacopoeial monograph for a substance includes the name of the substance in Russian and the chemical name in accordance with IUPAC rules. Below and in the center is the structural formula. In the empirical formula, carbon is written first, then hydrogen, and then all the elements in alphabetical order. If the relative molecular weight of the drug exceeds 400 amu, then it is indicated to the first decimal place, and if less, then to the second. The content of the main active ingredient is indicated in mass fractions, percentages or units of action (antibiotics). The following describes the nature of the drug and its physicochemical properties.

The “Description” section usually provides indicators of the drug’s appearance: its physical state (aggregate - amorphous or crystalline), shape and size of crystals, color, smell. Hygroscopicity and possible changes when stored in air or light are indicated.

The “Solubility” section indicates solubility in water, 95% ethanol, chloroform, ether and other solvents.

In the GF for most drugs, solubility is indicated in conventional terms:

The indicators given in the left column are very arbitrary. No matter how hard the drug researcher tries to remember all the given categories of solubility, in the end he will still have to turn to the classical quantitative (physicochemical) characteristic of solubility. Solubility usually means the concentration of a saturated solution of a substance at a certain temperature. In chemistry, the following solubility characteristics are used: soluble (more than 1 g in 100 g of solvent), slightly soluble (solubility from 1 mg to 1 g in 100 g of solvent), insoluble (solubility less than 1 mg in 100 g of solvent). The Pharmacopoeia considers seven solubility positions.

In the “Authenticity” section, the characteristics of UV and IR absorption spectra or other methods are indicated, as well as 2 - 3 chemical reactions that are most specific for a given drug.

When determining authenticity using chemical color reactions, group or specific reagents can be used. General (group) authenticity reactions can be used, for example, in the detection of aromatic amino compounds with the formation of aniline dyes.

A particular (specific) reaction to authenticity, for example, the determination of sodium ions in sodium chloride, is carried out by qualitative reactions to the presence of sodium ion - with zinccuranyl acetate or by flame color.

Temperature limits for distillation, melting and solidification temperatures, as well as density, specific rotation, specific absorption index, refractive index and other physical constants can be used as indicators of the authenticity and purity of a drug.

The section “Foreign (specific) impurities” provides detection methods and acceptable standards for technological impurities or impurities formed during storage. When using chromatography to detect impurities, indicate the type of sorbent, phase composition, amount of the test substance, development reagent and other chromatographic conditions.

Sources of impurities in medicinal products are varied. There are two types of impurities. “Hereditary” impurities enter drugs from poorly purified reagents, solvents, equipment materials, and excipients. For example, the preparation “Boric acid” may contain impurities of chlorides, sulfates, heavy metals, calcium, iron, arsenic, and borax. “Acquired” impurities are formed when storage conditions are not observed (for example, quinone impurity during the oxidation of phenol in the light). Impurities contained in a drug should not affect its physical, chemical properties and pharmacological activity.

An approximate (within certain limits) assessment of the content of some permissible impurities is carried out using standard solutions.

Reference method is based on the observation, under identical conditions, of the color or turbidity that occurs under the influence of any reagent on the test substance in comparison with a standard solution. The standard is a standard sample containing a certain amount of the impurity being determined. The presence of impurities is determined visually, by photocolorimetric or nephelometric methods. To do this, compare the results of reactions in the standard solution and in the drug solution after adding equal amounts of the corresponding reagents.

For example, for chloride tests, a reference solution is prepared by mixing solutions of sodium chloride and silver nitrate. A standard solution for sulfate ion is prepared by mixing barium chloride and potassium sulfate.

Many private articles of the Global Fund recommend the use of a reference method for determining impurities of organic substances. As a result of dehydration or oxidation under the action of sulfuric acid, colored products are formed. The intensity of the resulting color should not exceed the color intensity of the corresponding color standard.

Standards for determining the color of liquids are prepared from salts of cobalt(II), chromium(VI), copper(II) and iron(III). In this case, standard solutions of brown, yellow, pink and green shades are obtained. The color is observed on a white background.

To determine transparency, the liquid is viewed at an angle of 90° to the direction of the incident light (maximum light scattering according to Rayleigh's law). The test and reference solutions are placed in front of a black screen in comparison with the solvent. The standards for determining the degree of turbidity are suspensions obtained by mixing solutions of hydrazine sulfate and hexamethylenetetramine.

When performing purity tests, the general instructions provided by the Pharmacopoeia must be strictly followed. The water and reagents used must not contain detectable ions; the test tubes must be of the same diameter and colorless; the sample is taken with an accuracy of 0.001 g; reagents are added simultaneously and in equal quantities to the standard and test solutions.

It should be borne in mind that, unlike analytical chemistry, drugs are classified depending on the degree of purity not as “pure” (Pure), “pure for analysis” (analytical grade), “chemically pure” (CP) and “extra pure” ( Pure purity grade), but as substances of “pharmacopoeial quality”.

The section “Residual organic solvents” provides the results of determining the residual amounts of solvents if they were used in the drug manufacturing process.

In the sections “Chlorides”, “Sulfates”, “Sulfate ash and heavy metals” the permissible limits of these impurities are indicated, in the section “Arsenic” the permissible limits or requirements for the absence of arsenic are indicated.

The sections “Weight loss on drying” and “Water” indicate drying conditions, rates of weight loss on drying or moisture content.

One of the quality criteria is consistency of composition PM.

The drug can hydrolyze in the presence of moisture and when heated:

In this case, the composition of the drug changes. Irreversible changes in composition also occur during weathering - loss of crystallization water. In addition, the properties of drugs change when carbon dioxide is absorbed from the air.

The sections “Toxicity”, “Pyrogenicity”, “Content of substances with histamine-like action” indicate test doses, methods of administration, and period for observing the effect.

The section “Microbiological purity” describes the method for determining microorganisms and the permissible limits for their content.

The “Quantitative Determination” section provides a description of the method(s) for quantitative determination of the main substance contained in the drug, its mass fraction as a percentage or activity in units of action per milligram (IU/mg) when converted to the active substance.

This is followed by the sections “Packaging”, “Labelling”, “Transportation” and “Storage”. The last of the listed sections indicates the storage conditions that ensure the safety of the drug, the shelf life, and notes the storage features for drugs classified as poisonous, potent, psychotropic, and narcotic drugs.

The “Application” section contains information about the dosage forms of the drug, methods of administration and dosage.

1.3 Quality control requirements G.P.

All economically developed countries carry out pharmaceutical activities in accordance with GP (Good Practice) criteria. These rules have been applied in the USA since 1963 and relate to both production (GMP - Good Manufacturing Practice) and requirements for laboratory and clinical research or educational activities - GLP, GCP, GEP - (Laboratory, Clinical, Education respectively). The WHO certification system, based on GMP rules, is recognized in 140 countries around the world.

Thus, during the period of rapid development of the pharmaceutical industry, problems arose in the quality of finished medicines that could not be solved only by strengthening pharmacopoeial analysis. Ensuring the quality of drugs became possible only on the basis of GMP rules. The reason for their introduction was the use of thalidomide, a hypnotic with a teratogenic effect (congenital deformities).

In our time, the production of reproduced (generic) drugs, which required specific approaches to quality control, began to rapidly develop. Currently, the quality of finished drugs is determined not only by pharmacopoeial requirements, as was the case in the era of herbal medicines, but also by such pharmacokinetic characteristics as bioavailability and bioequivalence.

According to the GMP rules, the entire process of drug production, including premises, personnel, and documentation, becomes the object of control.

Good quality control practices for pharmaceuticals are ensured by a set of activities during their development and research, taking into account the requirements of not only GMP, but also GLP and GCP. Quality control includes quality control of raw materials, intermediate products, medicinal substances and finished dosage forms.

Each technique must contain a justification for its advantages in comparison with others in the form of presented comparative results of its application (validation).

Method validation includes the following metrological characteristics:

right(accuracy) - the closeness of the results to the true value, which can be carried out by comparison with the results obtained using another previously validated method;

accuracy(precision) - consistency between individual test results (deviation of individual results from the average value - relative standard deviation);

convergence(repeatability) - the accuracy of a technique when performed by the same analyst under the same conditions (reagents, equipment, laboratory);

reproducibility(reproducibility) - the accuracy of a technique when used under different conditions for identical samples taken from the same homogeneous series of material (different laboratories, performers, equipment, time).

reliability(robustness) - the ability of a technique to provide analytical results with acceptable accuracy and precision when operating conditions change for supposedly identical samples from the same homogeneous series of material;

sensitivity(sensitivity) - the ability of a test procedure to detect small changes in concentration (slope of the calibration curve);

detection limit(limit of detection) - the lowest content at which the analyte can be detected.

There is ongoing debate about the role of metrology in testing drugs at the preclinical and clinical levels, and in describing the effects of related substances in a drug, such as optical isomers. In the pharmacopoeial monograph, in the description of these tests, it is necessary to indicate the number of experiments during the analysis.

The issue of analytical reference materials (RMs) does not lose its relevance.

Main types of CO:

official СО - pharmacopoeial standard (state standard sample - GSO). This is a special series (batch) of a medicinal substance prepared in a certain way. GSO can be produced either by independent synthesis or using additional purification of the resulting substance. The reliability of a high degree of purity is established by analytical tests. Such a substance becomes the basis for creating a working standard sample;

working standard sample (RO) - a medicinal substance of established quality and purity, obtained with the help of a basic standard and used as a standard substance in the analysis of certain batches, new medicinal substances and new medicinal products.

Standardization of drugs at the international level (to establish uniformity in nomenclature, research methods, assessment of the quality of drugs, dosage of substances) is carried out by the United Nations World Health Organization (UN WHO), with the participation of which the publication of the International Pharmacopoeia was carried out.

Chapter 2. Pharmacopoeia of the USSR

2.1 History of domestic pharmacopoeias

The history of the creation of the first Russian pharmacopoeias begins in the second half of the 18th century.

In 1765, the Military Pharmacopoeia was published for the first time in Russia, and in 1778 the first official Russian State Pharmacopoeia was published.

The latter contained description 770 LP mineral, vegetable And animal origin, as well as multicomponent dosage forms.

In 1798, the second State Russian Pharmacopoeia was published, published, like the first, in Latin (translated into Russian in 1802).

After 1798, Military Pharmacopoeias (1808, 1812, 1818, 1840), Marine Pharmacopoeia (1864), Pharmacopoeias for the Poor (1807, 1829, 1845, 1860) and Court Pharmacopoeias (1825, 1872) were published in Russia. , 1874).

Each of the pharmacopoeias was a reflection of the level of development of pharmaceutical analysis. The first and second Russian pharmacopoeias recommended mainly organoleptic research methods (determination of color, smell, taste) and provided a description of the most important properties of drugs.

The publication in 1866 of a new edition of the Russian Pharmacopoeia was a historical milestone in the development of domestic pharmacy. This pharmacopoeia included 906 articles that described minerals, alkaloids, glycosides, plant materials, and finished drugs. A feature of the new pharmacopoeia was the inclusion in it, along with organoleptic chemical methods of drug control. The Pharmacopoeia of 1866 contains a list of potent drugs and the rules for their storage.

The Pharmacopoeia of 1866 became the first edition of the Russian Pharmacopoeia. Then II, III, IV, V, VI editions were published in 1871, 1880, 1891, 1902 and 1910, respectively.

The first edition of the Soviet pharmacopoeia, called the VII edition of the State Pharmacopoeia of the USSR (GP VII), was put into effect in July 1926. This pharmacopoeia differed from previous editions by its increased scientific level, the desire for the possible replacement of drugs made from imported raw materials with domestically produced drugs . GF VII included 116 articles on new drugs and excluded 112 articles. Significant changes have been made to the requirements for drug quality control. Instead of organoleptic control, a number of new methods of chemical and biological standardization of drugs were provided, 30 general articles were included in the form of appendices, descriptions of some general reactions used to determine the quality of drugs were provided, etc. Thus, in Global Fund VII, primary attention was paid to improving drug quality control. This principle was further developed in subsequent editions of the pharmacopoeia.

In 1949, the VIII edition was published, and in October 1961, the IX edition of the State Pharmacopoeia of the USSR was published.

The X edition of the State Pharmacopoeia (SP X) came into force on July 1, 1969. It reflected the new successes of domestic pharmaceutical and medical science and industry.

The fundamental difference between GF IX and GF X is the transition to new international drug terminology, as well as a significant update (by 30%) of its nomenclature. In GF X, the requirements for the quality of JIC have been significantly increased, and the scope of application of physicochemical methods has been expanded.

2.2 State Pharmacopoeia X

The tenth edition of the State Pharmacopoeia (GF X) contains an introductory part, two main parts and “Appendices”.

The first part - “Drugs” - includes individual articles that define the quality requirements for individual medicines, and group articles (tablets, injection solutions, extracts, herbs, tinctures, etc.).

The second part of the Pharmacopoeia contains a description of physicochemical, chemical, pharmacological and biological research methods, as well as reagents, titrated solutions and indicators.

The “Appendices” section contains tables of atomic weights, alcoholometric tables, drop tables, etc., as well as the highest single and daily doses of poisonous and potent drugs for adults and children and single, most commonly used doses of drugs for animals.

The tenth edition of the State Pharmacopoeia has a number of differences from the previous, IX edition.

The tenth edition of the State Pharmacopoeia contains 707 individual articles (in GF IX - 754) for various drugs and 31 group articles (in GF IX - 27).

219 private articles and 4 group articles were again included in Global Fund X; 235 articles contained in Global Fund IX are not included. The list of these articles is given on pages 23-25. 28 articles on vaccines and serums used in veterinary medicine were also excluded.

The requirements of GF IX for alcohols 90°, 70° and 40° are combined into one article, as well as the requirements for purified and precipitated sulfur.

The nomenclature of articles of the Global Fund X reflects the successes achieved in the creation and introduction of drugs into medical practice.

Global Fund X includes new synthetic drugs of various therapeutic groups: antibiotics, vitamins, hormones and other drugs. Outdated drugs that have been discontinued are excluded from the list. Also not included in the nomenclature are a number of drugs that have not been discontinued, but have limited use, and the quality of which does not differ from the requirements of the IX edition of the State Pharmacopoeia.

The quality of medicinal products not included in the State Fund X, but produced by industry, must be checked according to the relevant articles of the State Fund IX or the Inter-Republican Technical Specifications (MRTU 42).

GF X does not include tablets of complex composition (containing more than one active ingredient).

The articles in the “Drugs” section are placed in alphabetical order in accordance with their Latin names, with the exception of articles on dosage forms (injection solutions, tablets, ointments), which in this edition are placed after the article on the original medicinal substance.

The following sequence of titles is adopted in the headings of articles:

a) Latin name;

b) Russian name, which is an exact translation of the Latin name; in exceptional cases, names are given that deviate from the exact translation, but are generally accepted in the USSR;

c) synonyms: first - the main Latin and Russian synonyms used in the USSR, then the international Latin non-proprietary names recommended by the World Health Organization (WHO), if they do not coincide with the main Latin name of the Global Fund X.

International names are indicated by the symbol * and left without Russian translation.

In development of the nomenclatural principles laid down in the Global Fund IX, in the X edition of the Global Fund the Latin chemical name is given as the official name in the headings of articles in accordance with the principles recommended by WHO. Latin names, which were the main ones in GF IX, are included in the X edition of the State Pharmacopoeia as synonyms and are printed in bold below and to the left of the main Russian name. For the duration of the Global Fund X, these synonyms can be used by doctors when prescribing medications along with the main Latin names.

For ease of use of the Pharmacopoeia and the alphabetical index and the greatest correspondence between Latin and Russian chemical names in the headings of articles, the Russian name of the cation is placed first (for example, potassium bromide, sodium sulfate). In the alphabetical index, Russian chemical names are given starting with both the cation and the anion.

The main source of botanical names of species, genera and families given in the Global Fund X is, with rare exceptions, “Flora of the USSR”. In the names of pharmacognostic objects, as a rule, the rooted traditional names of plants are retained, even if they differ from the botanical names adopted in the “Flora of the USSR”.

Latin and Russian names of plant materials are given in the singular, except for “flowers” ​​- Flores, since this term means not only single flowers, but also inflorescences.

Russian names are adopted for reagents.

In order to achieve uniformity and consistency between individual groups of drugs, GF X introduced changes in the rational names and structural images (formulas) of drugs.

For salts of organic bases, the expanded name of the base in the genitive case is written in the first place, and the acid or acid radical in the nominative case is written in the second place.

The nomenclature of sulfonamide drugs remains the same as in SP IX, which corresponds to the generally accepted names of this class of compounds in the domestic chemical literature.

For gross formulas, the international system is adopted: carbon is written first, hydrogen second, the following elements, including metals, are arranged in alphabetical order.

Derivatives of acid radicals are depicted in detail.

The formulas of alkaloids, antibiotics, steroids and glycosides are depicted in planar form, but with a configurative designation.

For ease of use of the Pharmacopoeia, the structure of the articles in the new edition has been slightly changed (with the exception of articles on medicinal plant materials).

The “Properties” section has been replaced with 2 sections: “Description” and “Solubility”.

Due to the inclusion of a general article containing authenticity reactions for 25 ions and functional groups, a link to this article is provided for many drugs in specific articles. Some reactions to authenticity have been unified or replaced by new, more specific ones.

The “purity test” is divided into separate sections (chlorides, sulfates, etc.).

Instead of the two methods of quantitative determination that were available in a number of articles of the Global Fund IX, the new edition, as a rule, provides one method. In some cases, when GF X contains two methods and there are no special instructions, both methods are mandatory.

In GF X, the requirements for the quality of medicinal products have been increased in relation to both testing for purity and the quantitative content of the substance in the drug.

Many analysis methods available in GF IX have been clarified, changed and improved, and a number of new methods have been included.

For the first time, the following articles on methods of analysis are included in the Pharmacopoeia."

"General Reactions to Authenticity"

"Method of combustion in oxygen"

"Spectrophotometry in the infrared region" as a section of the article "Definitions based on measurements of light absorption",

"Fluorometry"

"Polarography"

"Nitritometry"

“Chromatography in a thin layer of sorbent” as a section of the article “Chromatography”

The articles have been revised and significantly changed: “Determination of arsenic”, “Determination of transparency and degree of turbidity of liquids”, “Determination of the color of liquids”, “Determination of density”, “Determination of melting point”, “Determinations based on measurement of light absorption”.

The articles have been updated: “Determination of the viscosity of liquids”, “Determination of the refractive index (refractometry)”, “Determination of optical rotation (polarimetry)”, “Determination of pH”, “Potentometric titration”, “Titration in non-aqueous solvents”, “Complexometric titration” , "Chromatography", "iodine number". The sections “Reagents” and “Indicators” have been expanded.

The use of new methods along with previously used methods for qualitative and quantitative testing of various drugs is envisaged.

The increased use of physicochemical methods of analysis has necessitated the development of reference materials for comparison. Therefore, the X edition of the Pharmacopoeia includes a general article “Reference Standards”, which provides the basic requirements for the quality of reference materials, which are approved by the Pharmacopoeial Committee of the USSR Ministry of Health in the form of MRTU 42 and are not included in the Pharmacopoeia. These requirements are based on the quality of existing international reference standards developed by the World Health Organization.

The new edition of the Pharmacopoeia clarifies and increases the quality requirements for a number of finished dosage forms.

New general articles have been introduced: “Eye drops” and “Granules”.

The rate at which tablets disintegrate has been changed from 10 to 15 minutes. The general article “Tablets” has been supplemented with requirements for enteric tablets. For coated tablets, separate articles indicate the weight of the tablet before coating.

For tablets, dragees, capsules and pills, a unified method for determining disintegration time is indicated.

The title of article GF IX “Dosage forms for injections” was changed to “Dosage forms for injections” and the names of private articles were changed accordingly.

For the articles “Dosage forms for injections” and “Eye drops”, a table of isotonic equivalents of medicinal substances for sodium chloride has been compiled, which is included in the “Appendices” section.

The article “Infusions and decoctions” is supplemented with a table of water absorption coefficients for various types of plant materials.

The article “Suppositories” includes a method for determining the complete deformation of suppositories.

In the article “Grinding and Sifting” the numbering of sieves is left in accordance with state standards.

In GF X, the articles “Techniques of microscopic research” and “Taking an average sample of plant materials” were significantly revised.

The general article on determining the biological activity of antibiotics has been clarified and expanded.

The new, X edition of the State Pharmacopoeia includes articles on some new endocrine drugs. To improve the quality of endocrine drugs, additional physical and chemical indicators have been included in a number of private articles.

Methods for determining the biological activity of insulin and assessing the duration of the effect of long-acting insulin preparations have been reworked. All methods require a mandatory comparison of the activity of the test and standard drugs and statistical processing of the data obtained.

Significant changes have been made to general articles that outline methods for determining the biological activity of endocrine drugs.

The article “Metopes for the analysis of bacterial preparations” was introduced for the first time in the Global Fund X.

Additionally, group-wide articles “Bacterial and Viral Allergens” and “Anatoxins” were included, and a number of new articles on serum-vaccine preparations were introduced. When compiling pharmacopoeial monographs, the requirements contained in the Inter-Republican Technical Specifications for these drugs, approved in 1960-1967, were taken into account. Ministry of Health of the USSR.

For the first time, GF X includes a section outlining methods of chemical analysis used to control vaccines, serums and toxoids.

The article “Biological methods for assessing the activity of medicinal plants and drugs containing cardiac glycosides” includes an additional section “Method of biological evaluation of cardiac drugs in pigeons.” Methods for determining drugs included in SP X for the first time (digitoxin, digitoxin tablets, celanide, etc.) are presented. Statistical analysis is used to evaluate the experimental results.

GF X includes a special general article “Statistical analysis of the results of biological tests”.

This edition has revised lists A (toxic) and B (potent) substances.

TO list A include medicines, the prescription, use, dosing and storage of which, due to their high toxicity, must be carried out with extreme caution. This list also includes drugs that cause addiction.

TO list B include medicines, the prescription, use, dosing and storage of which must be carried out with caution due to possible complications when used without medical supervision.

Storage and dispensing in pharmacies and all other institutions of medicines according to lists A and B are carried out in compliance with the rules given in special instructions approved by the USSR Ministry of Health.

The table of higher single and daily doses of toxic and potent drugs for adults has been revised, clarified and expanded. The table of the highest single and daily doses of poisonous and potent drugs for children has been updated. There is a table of single doses of poisonous, potent and some other medicines widely used in veterinary medicine for adult pets.

In the text of the articles, as well as in the IX edition of the Pharmacopoeia, only the highest single and daily doses for adults are indicated, the remaining doses are indicated in the tables.

At the end of the articles on the substances, instructions are given about the main pharmacological action. However, it should not be assumed that the substance cannot have another type of action or use.

The “Storage” section provides brief information about the conditions under which the drug should be stored (temperature; containers protected from light and moisture, etc.).

The expiration dates of drugs given in Global Fund IX are not indicated in this publication. These data are published in a separate document approved by the USSR Ministry of Health. The exceptions are ether for anesthesia, chloroform for anesthesia and some drugs containing cardiac glycosides, for which there is an indication of the period of re-control.

After the publication of GF X, a significant change in the nomenclature of drugs occurred, the requirements for their quality increased, and new highly effective methods of pharmacopoeial analysis were developed. The number of outdated, ineffective, and insufficiently harmless drugs excluded from the nomenclature was about 1000 items. All this required the Pharmacopoeial Committee to make appropriate additions and changes to the ND and create new FS.

2.3 State Pharmacopoeia X I

Since 1971, the Ministry of Health of the USSR approves a FS or VFS for each new drug and drug approved for use, and general pharmacopoeial monographs (GPM) for general methods of analysis. All of them have the same legal force and legislative character along with the Global Fund X. The work carried out was a preparatory stage for the release of the new, XI, edition of the Global Fund.

Issues have now been published. 1 and 2 GF XI. Vol. 1 by order of the USSR Ministry of Health was put into effect on January 1, 1988. Since that time, all previously valid ND, including the relevant articles of the Global Fund X, replaced by articles no. 1 GF XI.

The remaining materials contained in GF X (taking into account changes made to them in the prescribed manner) remain valid until the publication of the corresponding issues and articles of GF XI.

Unlike previous editions, the present eleventh edition of the State Pharmacopoeia (SP XI) is intended to be published in two parts, consisting of separate volumes with a sequential serial number.

Published individual pharmacopoeial monographs and volumes of the Global Fund XI are legally equivalent and have the same legal force.

Volume I of the State Fund XI "General methods of analysis" includes general articles on physical, physico-chemical, chemical methods of analysis and methods of analysis of medicinal plant raw materials - a total of 54 articles.

For the first time, 9 articles are introduced: "Gas chromatography" as a section of the general article "Chromatography", "High-performance liquid chromatography" as a section of the general article "Chromatography", "Method for determining the degree of whiteness of powdered drugs", "Phase solubility method", "Nuclear magnetic spectroscopy resonance", "Radioactivity", Electrophoresis",

“Emission and atomic absorption flame spectrometry”, “Luminescence microscopy”, “Determination of impurities of chemical elements in radiopharmaceuticals”.

The articles “Definition of the acetyl group” and “Reichert-Meissl number” contained in GF X are not included in GF XI. All other articles contained in the Global Fund X have been revised and supplemented taking into account modern scientific achievements in the field of drug analysis.

The article “Determination of transparency and degree of turbidity of liquids” has been significantly revised. To determine these indicators, new standards have been introduced - suspensions obtained from hydrazine sulfate and hexamethylenetetramine. A table for the preparation of standards and a diagram for viewing the transparency and degree of turbidity of liquids are provided.

The article “Complexometric Titration” has been revised and expanded to include a new indicator - calcone carboxylic acid, which has recently become widespread in pharmaceutical analysis. Complexons are increasingly used in analytical chemistry. Methods for determining cations of aluminum, bismuth, calcium, lead, magnesium and zinc have been introduced.

The article “Method of combustion in a flask with oxygen” includes methods for determining chlorine, bromine, fluorine, sulfur and phosphorus, which are currently widely used in analysis.

The article “General reactions to authenticity” has been significantly expanded. New sections have been introduced into it: “Iron oxide” and “Sulfites”; new identification methods are included in the sections “Iodides”, “Carbonates”, “Nitrates”, “Citrates”.

The article “Definitions based on measurements of the absorption of electromagnetic radiation” (section “Spectrophotometry in the ultraviolet and visible regions”) contains additions regarding the spectrophotometric analysis of multicomponent systems and includes a method of differential spectrophotometry.

The article “Determination of the color of liquids” has been significantly revised: a method for preparing 4 basic solutions from 4 initial solutions has been introduced; a ferric chloride solution was added to prepare one of the stock solutions.

The section “Measurement of viscosity on rotational viscometers” has been added to the article “Determination of the viscosity of liquids”. In the section "Measuring Viscosity with a Falling Ball Viscometer" the determination of viscosity using a Heppler viscometer is provided.

The article “Determination of volatile substances and water” has been revised and expanded: the sections “Drying method” and “Determination of water” have been clarified.

The section "Method of titration with K. Fisher's reagent" is supplemented with a method for determining the end of titration by electrometric titration "until the current completely stops."

The article “Determination of temperature limits of distillation” introduces a new device of the TPP type, with the help of which more accurate and reproducible results are obtained.

The article “Determination of Melting Point” introduces a PTP device with electrical heating to determine the melting point with a measurement range from 20 to 360 ° C.

The articles have been updated: “Determination of the refractive index”, “Fluorimetry”, “Determination of pH”, “Polarography”, “Solubility”, “Nitritometry”, “Iodine number”.

The article “Electrometric titration methods” in the section “Amperometric titration with two indicator electrodes (titration method “until the current completely stops”)” includes an addition to the measuring circuit, which allows, along with sensitive microammeters, to use industrially produced pH meters or ionometers.

In the article “Test for purity and permissible limits of impurities” the methods “Test for ammonium salts” and “Test for heavy metal salts” have been revised.

The article "Polarimetry" has been revised and clarified.

In the article “Determination of Nitrogen in Organic Compounds,” a change was made to the description of the device for determining nitrogen due to the improvement of the “funnel for introducing alkali.”

The article “Determination of solidification temperature” additionally indicates substances capable of supercooling.

The article "Statistical analysis of biological test results" has been significantly revised. The section "Statistical processing of chemical experiment results" has been added.

The section “Methods for analysis of medicinal plant raw materials” includes 7 group articles that define the main diagnostic characteristics for morphological groups of raw materials: “Leaves”, “Herbs”, “Flowers”, “Fruits”, “Seeds”, “Bark”, “Roots”, rhizomes, bulbs, tubers, corms", in which new sections "Luminescent microscopy" and "Histochemical reactions" are introduced (except for the article "Flowers"), and modern botanical terminology is also taken into account.

The article “Rules for the acceptance of medicinal plant raw materials and methods of sampling for analysis” includes for the first time the section “Sampling of packaged products.”

In the article “Determination of essential oil content in medicinal plant raw materials,” along with the three methods adopted by the State Fund X, a fourth determination method (Clevenger’s method as modified) was introduced.

All other articles have been revised and supplemented taking into account modern requirements for the quality of medicinal plant raw materials.

Issue 2 of the State Fund XI includes 2 sections: “General methods of analysis” and “Medicinal plant raw materials”.

The section “General methods of analysis” includes 40 articles, 6 of which are for the first time: “Determination of the activity of enzyme preparations”, “Determination of protein in enzyme preparations”, “Methods for the quantitative determination of vitamins in dosage forms”, “Aerosols”, “Suspensions” and "Test for microbiological purity."

The remaining articles have been revised and supplemented taking into account modern advances in the field of drug analysis. Thus, for the first time, the article “Sterilization” additionally introduced the method of sterilization through membrane and depth filters, as well as the radiation method.

In the article “Determination of the grinding of powders and sieves,” for the first time, along with silk fabric for sieves, the use of nylon fabric is provided. The article describes the characteristics of the sieves used for analysis when determining the grinding of medicinal plant raw materials.

In the article “Determination of Zinc in Insulin Preparations,” instead of the photocolorimetric method with dithizone, the spectrophotometric method with zincone and atomic absorption method were introduced.

In the article “Determination of preservatives in hormonal preparations,” the gas chromatography method was first introduced to determine phenol and nipagin.

The article “Reference Standards” provides definitions of the terms “State Standard Samples” (GSO), “Working Standard Samples” (RSO) and “Reference Standard Samples of Witness Substances”, indicating their areas of application and requirements for their quality.

The article “Titrated solutions” has been revised in connection with the introduction of the SI system and IUPAC recommendations. The basic SI unit of quantity of a substance is the mole, so “normal” solutions are converted to “molar” solutions. This article, in the “General Notes” section, provides definitions of molarity, titer, mole, a definition of the term “conventional particle” (CP), and basic instructions for the preparation and storage of molar solutions.

The article “Indicators” has been revised and clarified: a definition of the concept “indicators” has been introduced, requirements for the preparation and storage of indicator solutions and dry indicator mixtures, and safety rules when working with indicators. The section "Indicator paper" has been introduced; The documentation for the indicators is provided.

The article "Reagents" has been revised and clarified. A “Note” has been introduced indicating which reagent grade should be used when analyzing medicinal products. Documentation for reagents is provided.

Due to the fact that the articles “Titrated solutions”, “Indicators” and “Reagents” of the 2nd issue of the State Pharmacopoeia of the USSR XI edition include titrated solutions, indicators and reagents given in the 1st issue, but in an updated version, it follows When using private pharmacopoeial monographs, be guided by the relevant articles published in the 2nd issue.

The general article "Granules" includes a description of coated granules; a requirement has been introduced to determine moisture (in accordance with private articles). The disintegration and dissolution of granules is intended to be determined using the devices specified in the article “Tablets”.

The article “Injectable dosage forms” introduces a requirement for the manufacture of medicines for parenteral use under conditions that maximally prevent contamination of the finished product by microorganisms and foreign substances.

A requirement has been introduced for individual injection solutions to be isohydric and isotonic; the type of excipients has been specified. Some excipients have permissible amounts; for example, for substances like chlorobutane, cresol, phenol - up to 0.5%; sulfites - up to 0.2%.

A requirement is included on the inadmissibility of the presence of preservatives in drugs for intracavitary, intracardiac, intraocular administration or in injection dosage forms administered into the spinal canal, as well as for a single dose exceeding 15 ml. It is prohibited to introduce the suspension into blood and lymphatic vessels, as well as the introduction of suspensions and emulsions into the spinal canal.

The article "Injectable dosage forms" provides a definition of clarity in comparison with water for injection or an appropriate solvent.

Additional requirements have been introduced for testing for toxicity, as well as for pyrogenicity, with a single dose volume of 10 ml or more, as well as with a smaller dose, if indicated in a private article.

Requirements have been introduced regarding dosing accuracy and permissible deviations in the mass of a substance in a dose of dry medicines for parenteral use. For contents weighing 0.05 g or less, a dosage uniformity test is required.

For suspensions administered parenterally, the time of sedimentation stability is indicated, and instructions are given for passage into the syringe through a needle No. 0840.

For the first time, a requirement has been introduced for the mandatory application of a batch number on an ampoule (vessel) of any capacity.

The article “Eye Drops” introduces a method of sterilization and sterility testing; The list of excipients has been expanded. Additional requirements for the packaging of drops are given.

The article “Capsules” includes a definition of the average weight for capsules containing 0.05 g or less of a medicinal substance.

A test for dosage uniformity is also provided, the definition of disintegration is clarified, and a definition of dissolution (release) is included.

The general article “Ointments” provides the actual ointments, pastes, creams, gels and liniments. The classification of ointment bases is given; in the absence of indications on the base, it is recommended to choose it taking into account the physical and chemical compatibility of the ointment components. The article contains instructions on the sterility of eye ointments. A microscopic method has been introduced for determining the degree of dispersion of the solid phase in suspension ointments.

The article “Suppositories” provides for the standardization of the weight of suppositories for children (from 0.5 to 1.5 g) and their size (with a diameter of no more than 1 cm). For suppositories made on hydrophilic bases, a new “dissolution” indicator has been introduced. The requirements regarding the determination of the deviation of the suppository weight from the average value have been clarified. For suppositories made on polyethylene oxide bases, a requirement is included for the need to wet the suppositories before insertion into the body cavity.

The article “Tablets” has been supplemented with requirements for tablets for parenteral use and an indication of the sterility of tablets for implantation. The list of excipients has been updated. The permissible norm for aerosil content has been introduced.

The requirements for fluctuations in the average weight of tablets and the content of medicinal substances have been clarified. Dosage uniformity testing is included for uncoated tablets containing 0.05 g or less of drug substance and for coated tablets containing 0.01 g or less of drug substance. A determination of the abrasion strength of uncoated tablets has been introduced.

The definition of disintegration has been clarified and a definition of dissolution (release) has been included.

The article “Biological methods for assessing the activity of medicinal plants and preparations containing cardiac glycosides” provides a general description of methods for biological assessment in frogs, cats and pigeons, and a detailed description of methods for determining the biological activity of each of the medicinal plants and preparations containing cardiac glycosides is given in private pharmacopoeial monographs.

Statistical processing of the results of biological tests is carried out taking into account the requirements of the Global Fund XI, no. 1, Art. "Statistical processing of the results of chemical experiments and biological tests."

In the article “Determination of the biological activity of insulin,” along with the ferricyanide method, the glucose oxidase method for determining blood glucose was introduced for the first time as the most specific and widespread.

In comparison with the article of the State Pharmacopoeia X, some changes and additions have been made to the article “Toxicity Test” related to the ever-increasing requirements for the quality of medicines and, accordingly, the standardization of their test conditions. The mass of animals on which the test is carried out (both initial and repeated) has been increased. To more strictly standardize the test results, the conditions for keeping the animals are indicated, as well as the period of observation for them (48 hours). The article includes a "Sampling" section.

The article “Pyrogenicity Test” contains an indication that the use of albino rabbits is inadmissible. Testing for the reactivity of rabbits intended for drug testing for the first time has been introduced. The section on the possibility of reusing rabbits to determine pyrogenicity has been clarified.

The section “Methods for microbiological control of medicinal products” includes articles “Test for sterility”, “Nutrient media”, “Test for microbiological purity” and “Quantitative determination of microorganisms”. The articles unify sampling for analysis, incubation temperature, methods for determining the antimicrobial effect of drugs, recording results, etc.

A membrane filtration method has been introduced to determine the sterility of drugs with a pronounced antimicrobial effect and drugs produced in containers larger than 100 ml.

The article “Sterility Test” has been significantly revised and supplemented. To determine this indicator, two nutrient media were added (thioglycolate and Sabouraud), and the incubation time of the crops was increased to 14 days.

The article “Test for microbiological purity” provides for the determination of the total number of bacteria and fungi in non-sterile medicinal products, as well as the identification of contaminating flora - representatives of Escherichia coli and staphylococcus, the presence of which is excluded. The limits of permissible microbial contamination in relation to bacteria and fungi are given.

The article “Determination of the antimicrobial activity of antibiotics by diffusion in agar” has been revised and expanded, in which two methods are presented (three-dose and using a standard curve) and determination conditions are given.

The second section, “Medicinal plant materials,” includes one general and 83 specific articles on medicinal plant materials, widely used in medical practice for the preparation of herbal infusions and decoctions, as well as for the production of medicines in industrial production.

Compared to the X edition of the State Pharmacopoeia of the USSR, the nomenclature of medicinal plant raw materials has been significantly expanded, species not included in previous editions are included, as well as new species approved for medical use: rhizomes with roots of Rhodiola rosea, shoots of wild rosemary, common spruce cones, seaweed , rhizomes with madder roots, etc.

For some types of medicinal plant raw materials, along with those used, other botanical species of the same genus, approved for medical use, are included (for example, various types of hawthorn, rose hips).

The name of the raw material is given in the plural (leaves, roots, etc.).

The nomenclature of the names of producing plants is unified and brought into line with their modern scientific Russian and Latin names (Article 3 of the rules of the International Code of Botanical Nomenclature, 1980 edition). In a number of cases, the interpretation of the taxonomic volume of some genera and species has changed: large polymorphic taxa are considered as narrower ones (Padus avium = P. avium + P. asiatica) and, conversely, previously understood as isolated closely related taxa, are combined into species or genera of enlarged volume (Aralia mandshurica) --> A. elata).At the same time, taking into account the established traditional names of raw materials, in this edition of the pharmacopoeia it was decided not to change them, but in some cases to give a second Latin name according to the genus and species of the producing plant.

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