The biological assessment of the quality of drugs is usually carried out according to the strength of the pharmacological effect or toxicity. Biological methods are used when physical, chemical or physico-chemical methods fail to make a conclusion about the purity or toxicity of the medicinal product, or when the method of preparation of the drug does not guarantee the constancy of activity (for example, antibiotics).
Biological tests are carried out on animals (cats, dogs, rabbits, frogs, etc.), individual isolated organs (uterine horn, part of the skin), individual groups of cells (blood cells), as well as on certain strains of microorganisms. The activity of drugs is expressed in units of action (ED).
Biological control of drugs containing cardiac glycosides. According to SP XI, a biological assessment of the activity of medicinal plant materials and preparations derived from it containing cardiac glycosides, in particular foxglove (purple, large-flowered and woolly), adonis, lily of the valley, strophanthus, gray jaundice, is carried out. Tests are carried out on frogs, cats and pigeons, setting the frog (ICE), feline (CED) and pigeon (CED) action units, respectively. One ICE corresponds to the dose of the standard sample, which, under experimental conditions, causes systolic cardiac arrest in the majority of experimental standard frogs (males weighing 28–33 g). One KED or GED corresponds to the dose of a standard sample or test drug per 1 kg of animal or bird weight that causes systolic cardiac arrest in a cat or pigeon. The ED content is calculated in 1.0 g of the study drug, if plant materials or dry concentrates are tested; in one tablet or in 1 ml if liquid dosage forms are being tested.
Toxicity test. In this section GF XI, no. 2 (p. 182), in comparison with SP X, a number of additions and changes have been made, reflecting the increasing requirements for the quality of medicines and the need to unify the conditions for their testing. The article includes a section that describes the procedure for sampling. The mass of animals on which the test is carried out has been increased, the conditions for their maintenance and the period of observation of them have been indicated. To perform the test, two vials or ampoules are selected from each batch containing not more than 10,000 vials or ampoules. From parties with a large number, three ampoules (vials) are selected from each series. The contents of samples of one series are mixed and tested on healthy white mice of both sexes weighing 19–21 g. The test solution is injected into the tail vein of five mice and animals are observed for 48 hours. The drug is considered to have passed the test if none of the experimental mice die in within the specified period. In the event of the death of even one mouse, the test is repeated according to a certain scheme. Private articles may also specify a different procedure for conducting a toxicity test.
Pyrogenicity tests. Bacterial pyrogens are substances of microbial origin that can cause in humans and warm-blooded animals when they enter the blood channel fever, leukopenia, drop in blood pressure and other changes in various organs and systems of the body. The pyrogenic reaction is caused by gram-negative living and dead microorganisms, as well as their decay products. Permissible content, for example, in an isotonic solution of sodium chloride, 10 microorganisms per 1 ml, and with the introduction of not more than 100 ml, 100 per 1 ml are allowed. The test for pyrogenity is subjected to water for injection, injection solutions, immunobiological drugs, solvents used for the preparation of injection solutions, as well as dosage forms that cause, according to clinics, a pyrogenic reaction.
In SP XI, as well as in the pharmacopoeias of other countries of the world, a biological method for testing pyrogenicity is included, based on measuring the body temperature of rabbits after the introduction of test sterile liquids into the ear vein. Sampling is carried out in the same way as in the toxicity test. The general article (GF XI, issue 2, pp. 183--185) specifies the requirements for experimental animals and the procedure for their preparation for testing. The test solution is tested on three rabbits (not albino), whose body weight differs by no more than 0.5 kg. Body temperature is measured by inserting a thermometer into the rectum to a depth of 5--7 cm. The test liquids are considered non-pyrogenic if the sum of elevated temperatures in three rabbits is equal to or less than 1.4°C. If this amount exceeds 2.2°C, then water for injection or injection solution is considered pyrogenic. If the sum of the temperature rises in three rabbits is between 1.5 and 2.2°C, the test is repeated in an additional five rabbits. The test fluids are considered non-pyrogenic if the sum of the temperature rises in all eight rabbits does not exceed 3.7°C. In private FS, other temperature deviation limits may be specified. Rabbits that were in the experiment can be used for this purpose again no earlier than 3 days later, if the solution introduced by them was non-pyrogenic. If the injected solution turned out to be pyrogenic, then rabbits can be reused only after 2-3 weeks. In SP XI, in comparison with SP X, a test for the reactivity of rabbits used for the first time for testing has been introduced, and the section on the possibility of their use for repeated tests has been clarified.
The recommended SP XI biological method is specific, but does not quantify the content of pyrogenic substances. Its significant disadvantages include the complexity and duration of testing, the need to keep animals, care for them, the complexity of preparing for testing, the dependence of the results on the individual characteristics of each animal, etc. Therefore, attempts were made to develop other methods for determining pyrogenicity.
Along with the determination of pyrogenicity in rabbits, a microbiological method is used abroad, based on counting the total number of microorganisms in the studied dosage form before its sterilization. In our country, a simple and accessible method for the detection of pyrogens has been proposed, based on the selective identification of gram-negative microorganisms by the gel formation reaction using a 3% potassium hydroxide solution. The technique can be used at chemical and pharmaceutical enterprises.
An attempt was made to replace the biological method for determining pyrogenicity with a chemical one. Solutions containing pyrogens, after treatment with quinone, showed a negative reaction with tetrabromophenolphthalein. Pyrogenal with tryptophan in the presence of sulfuric acid forms a brown-raspberry color at a pyrogenal content of 1 μg or more.
The possibility of spectrophotometric determination of pyrogenic substances in the UV region of the spectrum was investigated. Solutions of the filtrate of pyrogen-containing cultures of microorganisms show a weak absorption maximum at 260 nm. In terms of sensitivity, the spectrophotometric method for determining pyrogens is 7-8 times inferior to the biological test on rabbits. However, if ultrafiltration is carried out before spectrophotometry, then due to the concentration of pyrogens, comparable results can be achieved by biological and spectrophotometric determinations.
After treatment with quinone, pyrogen solutions acquire a red color and a light absorption maximum appears at 390 nm. This made it possible to develop a photocolorimetric method for the determination of pyrogens.
The high sensitivity of the luminescent method created the prerequisites for its use for the determination of pyrogenic substances at concentrations up to 1*10 -11 g/ml. Methods have been developed for the luminescent detection of pyrogens in water for injection and in some injection solutions using the dyes rhodamine 6G and 1-anilino-naphthalene-8-sulfonate. The techniques are based on the ability of pyrogens to increase the intensity of the luminescence of these dyes. They allow you to get results comparable to the biological method.
The relative error of the spectrophotometric and luminescent determinations does not exceed ±3%. The chemiluminescent method is also used to determine the pyrogenicity of water for injection.
A promising method is polarography. It has been established that filtrates of pyrogenic cultures, even in a very dilute state, have a strong suppressive effect on the polarographic maximum of oxygen. On this basis, a method has been developed for the polarographic assessment of the quality of water for injection and some injection solutions.
Test for the content of histamine-like substances.
Parenteral medicinal products are subjected to this test. Perform it on cats of both sexes weighing at least 2 kg under urethane anesthesia. First, an anesthetized animal is injected with histamine, testing its sensitivity to this substance. Then, with an interval of 5 minutes, repeated injections (0.1 μg/kg) of the standard solution of histamine are continued until the same decrease in blood pressure is obtained with two successive injections, which is taken as standard. After that, with an interval of 5 minutes, the test solution is administered to the animal at the same rate as the histamine was administered. The drug is considered to have passed the test if the decrease in blood pressure after the introduction of the test dose does not exceed the response to the introduction of 0.1 µg/kg in the standard solution.
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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
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. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ………..nine
1.4.2. Features of quantitative express analysis. . . . . . . . …nine
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
1.2 Errors in Pharmaceutical Analysis
1.3 General principles for testing the identity of medicinal substances
1.4 Sources and causes of poor quality of medicinal substances
1.5 General requirements for purity tests
1.6 Methods of pharmaceutical analysis and their classification
Chapter 2. Physical Methods of Analysis
2.1 Verification of physical properties or measurement of physical constants of drug substances
2.2 Setting the pH of the medium
2.3 Determination of clarity and turbidity of solutions
2.4 Estimation of chemical constants
Chapter 3. Chemical Methods of Analysis
3.1 Features of chemical methods of analysis
3.2 Gravimetric (weight) method
3.3 Titrimetric (volumetric) methods
3.4 Gasometric analysis
3.5 Quantitative elemental analysis
Chapter 4. Physical and chemical methods of analysis
4.1 Features of physicochemical methods of analysis
4.2 Optical methods
4.3 Absorption methods
4.4 Methods based on emission of radiation
4.5 Methods based on the use of a magnetic field
4.6 Electrochemical methods
4.7 Separation methods
4.8 Thermal methods of analysis
Chapter 5
5.1 Biological quality control of medicines
5.2 Microbiological control of medicinal products
List of used literature
Introduction
Pharmaceutical analysis is the science of chemical characterization and measurement of biologically active substances at all stages of production: from the control of raw materials to the assessment of the quality of the resulting medicinal substance, the study of its stability, the establishment of expiration dates and the standardization of the finished dosage form. Pharmaceutical analysis has its own specific features that distinguish it from other types of analysis. These features lie in the fact that substances of various chemical nature are subjected to analysis: inorganic, organoelement, radioactive, organic compounds from simple aliphatic to complex natural biologically active substances. The range of concentrations of analytes is extremely wide. The objects of pharmaceutical analysis are not only individual medicinal substances, but also mixtures containing a different number of components. The number of medicines is increasing every year. This necessitates the development of new methods of analysis.
Methods of pharmaceutical analysis need to be systematically improved due to the continuous increase in the requirements for the quality of drugs, and the requirements for both the degree of purity of medicinal substances and the quantitative content are growing. Therefore, it is necessary to widely use not only chemical, but also more sensitive physical and chemical methods to assess the quality of drugs.
The requirements for pharmaceutical analysis are high. It should be sufficiently specific and sensitive, accurate in relation to the standards stipulated by GF XI, VFS, FS and other scientific and technical documentation, carried out in short periods of time using minimal quantities of tested drugs and reagents.
Pharmaceutical analysis, depending on the tasks, includes various forms of drug quality control: pharmacopoeial analysis, step-by-step control of the production of medicines, analysis of individual dosage forms, express analysis in a pharmacy, and biopharmaceutical analysis.
Pharmacopoeial analysis is an integral part of pharmaceutical analysis. It is a set of methods for the study of drugs and dosage forms set forth in the State Pharmacopoeia or other regulatory and technical documentation (VFS, FS). Based on the results obtained during the pharmacopoeial analysis, a conclusion is made on the compliance of the medicinal product with the requirements of the Global Fund or other regulatory and technical documentation. In case of deviation from these requirements, the drug is not allowed to be used.
The conclusion about the quality of the medicinal product can only be made on the basis of the analysis of the sample (sample). The procedure for its selection is indicated either in a private article or in a general article of the Global Fund XI (issue 2). Sampling is carried out only from undamaged sealed and packed in accordance with the requirements of the NTD packaging units. At the same time, the requirements for precautionary measures for working with poisonous and narcotic drugs, as well as for toxicity, flammability, explosiveness, hygroscopicity and other properties of drugs, must be strictly observed. To test for compliance with the requirements of the NTD, multi-stage sampling is carried out. The number of steps is determined by the type of packaging. At the last stage (after control by appearance), a sample is taken in the amount necessary for four complete physical and chemical analyzes (if the sample is taken for controlling organizations, then for six such analyzes).
From the "angro" packaging, point samples are taken, taken in equal quantities from the top, middle and bottom layers of each packaging unit. After establishing homogeneity, all these samples are mixed. Loose and viscous drugs are taken with a sampler made of an inert material. Liquid medicinal products are thoroughly mixed before sampling. If this is difficult to do, then point samples are taken from different layers. The selection of samples of finished medicinal products is carried out in accordance with the requirements of private articles or control instructions approved by the Ministry of Health of the Russian Federation.
Performing a pharmacopoeial analysis allows you to establish the authenticity of the drug, its purity, to determine the quantitative content of the pharmacologically active substance or ingredients that make up the dosage form. While each of these stages has a specific purpose, they cannot be viewed in isolation. They are interrelated and complement each other. For example, melting point, solubility, pH of an aqueous solution, etc. are criteria for both authenticity and purity of a medicinal substance.
Chapter 1. Basic Principles of Pharmaceutical Analysis
1.1 Pharmaceutical analysis criteria
At various stages of pharmaceutical analysis, depending on the tasks set, such criteria as selectivity, sensitivity, accuracy, time spent on the analysis, and the amount of the analyzed drug (dosage form) are important.
The selectivity of the method is very important when analyzing mixtures of substances, since it makes it possible to obtain the true values of each of the components. Only selective methods of analysis make it possible to determine the content of the main component in the presence of decomposition products and other impurities.
Requirements for the accuracy and sensitivity of pharmaceutical analysis depend on the object and purpose of the study. When testing the degree of purity of the drug, methods are used that are highly sensitive, allowing you to set the minimum content of impurities.
When performing step-by-step production control, as well as when conducting express analysis in a pharmacy, an important role is played by the time factor spent on the analysis. For this, methods are chosen that allow the analysis to be carried out in the shortest time intervals and at the same time with sufficient accuracy.
In the quantitative determination of a medicinal substance, a method is used that is distinguished by selectivity and high accuracy. The sensitivity of the method is neglected, given the possibility of performing an analysis with a large sample of the drug.
A measure of the sensitivity of a reaction is the limit of detection. It means the lowest content at which the presence of the determined component can be detected by this method with a given confidence level. The term "limit of detection" was introduced instead of such a concept as "discovered minimum", it is also used instead of the term "sensitivity". The sensitivity of qualitative reactions is influenced by such factors as the volumes of solutions of reacting components, concentrations of reagents, pH of the medium, temperature, duration experience.This should be taken into account when developing methods for qualitative pharmaceutical analysis.To establish the sensitivity of reactions, the absorbance index (specific or molar) established by the spectrophotometric method is increasingly used.In chemical analysis, the sensitivity is set by the value of the limit of detection of a given reaction.Physicochemical methods are distinguished by high sensitivity analysis The most highly sensitive are radiochemical and mass spectral methods, which allow determining 10 -8 -10 -9% of the analyte, polarographic and fluorimetric 10 -6 -10 -9%, sensitivity of spectrophotometric methods is 10 -3 -10 -6%, potentiometric 10 -2%.
The term "analysis accuracy" simultaneously includes two concepts: reproducibility and correctness of the obtained results. Reproducibility characterizes the scatter of the results of an analysis compared to the mean. Correctness reflects the difference between the actual and found content of the substance. The accuracy of the analysis for each method is different and depends on many factors: the calibration of measuring instruments, the accuracy of weighing or measuring, the experience of the analyst, etc. The accuracy of the analysis result cannot be higher than the accuracy of the least accurate measurement.
5 / 5 (votes: 1 )
Today, it is quite common to find low-quality medicines and dummy pills that cause the consumer to doubt their effectiveness. There are certain methods of drug analysis that allow to determine the composition of the drug, its characteristics with maximum accuracy, and this will reveal the degree of influence of the drug on the human body. If you have certain complaints about a drug, then its chemical analysis and objective opinion can be evidence in any legal proceeding.
What methods of drug analysis are used in laboratories?
To establish the qualitative and quantitative characteristics of a drug in specialized laboratories, the following methods are widely used:
- Physical and physico-chemical, which help determine the melting and solidification temperature, density, composition and purity of impurities, find the content of heavy metals.
- Chemical, determining the presence of volatile substances, water, nitrogen, the solubility of the medicinal substance, its acid, iodine number, etc.
- Biological, allowing you to test the substance for sterility, microbial purity, the content of toxins.
Methods for the analysis of medicines will make it possible to establish the authenticity of the composition declared by the manufacturer and determine the slightest deviations from the norms and production technology. The laboratory of ANO "Center for Chemical Expertise" has all the necessary equipment for an accurate study of any type of medicine. Highly qualified specialists use a variety of methods for analyzing medicines and will provide an objective expert opinion in the shortest possible time.
Methods for the study of medicinal substances are divided into:
1. physical,
2. chemical,
3. physical and chemical,
4. biological.
Physical methods of analysis involves the study of the physical properties of a substance without resorting to chemical reactions. These include: determination of solubility, transparency or degree of turbidity, color; determination of density (for liquid substances), humidity, melting point, solidification point, boiling point.
Chemical research methods based on chemical reactions. These include: determination of ash content, reaction of the environment (pH), characteristic numerical indicators of oils and fats (acid number, iodine number, saponification number, etc.). For the purposes of identifying medicinal substances, only such reactions are used that are accompanied by a visual external effect, for example, a change in the color of the solution, evolution of gases, precipitation or dissolution of precipitates, etc. Chemical research methods also include weight and volume methods of quantitative analysis adopted in analytical chemistry (method of neutralization, precipitation, redox methods, etc.). In recent years, pharmaceutical analysis has included such chemical research methods as titration in non-aqueous media, complexometry. Qualitative and quantitative analysis of organic medicinal substances, as a rule, is carried out by the nature of the functional groups in their molecules.
Via physical and chemical methods study the physical phenomena that occur as a result of chemical reactions. For example, in the colorimetric method, the color intensity is measured depending on the concentration of a substance, in the conductometric analysis, the measurement of the electrical conductivity of solutions, etc.
Physical and chemical methods include: optical (refractometry, polarimetry, emission and fluorescent methods of analysis, photometry, including photocolorimetry and spectrophotometry, nephelometry, turbodimetry), electrochemical (potentiometric and polarographic methods), chromatographic methods.
biological this is an animal study (frogs, pigeons, cats). Defined in units. Subjected to: MPS containing cardiac glycosides, drugs containing hormones, enzymes, vitamins, antibiotics.
Registration of extemporaneous drugs, VAZ, VAF is carried out in accordance with the order of the Ministry of Health of the Russian Federation No. 376 and guidelines on a single design.
Labels for the design of medicines prepared individually and in the order of intra-pharmacy preparation and packaging, depending on the method of their use, are divided into:
ü labels for drugs for internal use with the inscription "Internal", "Internal for children";
ü labels for drugs for external use with the inscription "External";
ü labels for drugs for parenteral administration with the inscription "For injection";
ü labels for eye medicines with the inscription "Eye drops", "Eye ointment".
On all labels for the design of medicines, prepared individually and in the order of in-pharmacy preparation and packaging, warning labels corresponding to each dosage form must be printed in a typographical way:
ü for potions - "keep in a cool and dark place", "shake before use";
ü for ointments, eye ointments and eye drops - "keep in a cool and dark place";
ü for drops of internal use - "keep in a place protected from light";
ü for injections - "sterile".
All labels must contain the warning "Keep out of the reach of children".
The dosage form is indicated by hand.
All labels for the design of medicines prepared in the order of in-pharmacy procurement and packaging must have the following designations:
ü emblem (bowl with a snake);
ü location of the pharmacy institution (enterprise);
ü the name of the pharmacy institution (enterprise);
ü method of application (internal, external, for injection) or dosage form (ointment, eye drops, nose drops, etc.);
date of preparation...;
ü good for ...;
ü series...;
ü Keep away from children.
The text of pharmacy labels intended for the design of medicines prepared individually, as well as the method of application, must be printed in Russian or the local language.
The text of pharmacy labels intended for the design of medicines prepared in the order of in-pharmacy preparation and packaging, as well as their names and necessary warning labels, is recommended to be printed in a typographical way.
Warning labels affixed to medicines have the following text and signal colors:
ü "shake before use" - green font on a white background;
ü "keep in a place protected from light" - white font on a blue background;
ü "keep in a cool place" - white font on a blue background;
ü "childish" - white font on a green background;
ü "for newborns" - white font on a green background;
ü "handle with care" - red font on a white background;
ü "heart" - white font on an orange background;
ü "Keep away from fire" - white font on a red background.
Particularly toxic substances (<...>, cyanide and mercury oxycyanide) are issued with one black warning label with the name of the poisonous drug in Russian (or local) language in white font with the image of crossbones and a skull and the inscription "poison" and "handle with care" in accordance with the current order.
Registration of medicines prepared in pharmacies (enterprises) of various forms of ownership, in accordance with the presented Uniform Rules for the Registration of Medicines, contributes to improving the culture of drug supply to the population, strengthening control over the expiration dates of prepared medicines and their price, drawing attention to them in order to eliminate possible errors in their use.
Determination of tariffs
The payment includes:
1. The cost of drugs
2. Cost of auxiliary materials
3. Cost of dishes
4. Costs
Tariffs are approved by order of the pharmacy.
The initial data for determining production costs are the accounting and reporting data of the pharmacy for the past month.
The number of conditional production units reflects the total labor intensity of manufacturing one unit of a medicinal product and medical devices.
For one production unit, the work performed within 10 minutes is conditionally accepted.
For one unit of production of sterile and liquid dosage forms, ointments, a medicinal product is accepted, fully prepared in accordance with the current documents and intended for dispensing.
Sterile dosage forms include injectable solutions, infusion solutions, ophthalmic irrigation solutions, neonatal solutions and oils.
To ZhLF include solutions and drops for internal use and external use, oils, purified water.
Ointments include pastes, liniments, liquid plasters, suspensions, emulsions.
For one unit of powders and suppositories, a dosage form with packaging for 10 doses is conventionally accepted.
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