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The present study focuses on the use of surfactants (SA) in quality control of solid dosage forms. Features of the dissolution of solid dosage forms and factors affecting the extraction of microorganisms from drug samples are discussed. The properties of SA required to neutralize the antimicrobial activity of drugs are considered. Experimental data on the extraction of microorganisms from and the neutralization of antimicrobial action of solid dosage forms of non-sterile drugs are presented.

An informational-analytical review of alternative microbiological methods for quality testing of pharmaceutical products is presented. The expediency and peculiarities of implementing these methods in pharmacy practice for routine testing are considered. General approaches to validation of new methods are described. The new methods are compared with classical methods in all implementation stages. Foreign regulations on the selection of validation parameters and their acceptance criteria are analyzed.

Materials related to features of microbiological analysis of the purity of soft dosage forms are presented. Possible requirements for microbiological quality parameters of various soft dosage forms are analyzed. The applicability of a direct inoculation technique to obtain reliable quantitative determinations of microorganisms is proven using gel, ointment, and suppositories as examples. The accuracy (Kgr 75 – 107%) and intralaboratory precision (CV 2 – 6%) are calculated and fall within the required limits. The specificity of the method is considered for a particular working range established according to recommendations of the RF State Pharmacopoeia, i.e., up to 250 CFU/dish for bacteria and up to 50 CFU/dish for yeasts and molds. Features of microbiological analysis of the quality of patches and transdermal therapeutic systems are studied. The possibilities and limitations of a membrane filtration technique are shown using 83 series of 18 items meeting regulatory requirements as examples.

The possibility of reducing the sample size for microbiological examination of some pharmaceutical substances is considered. Trypticase-soy agar was evaluated for the ability to detect yeast and mold fungi and to isolate the minimal amount of certain types of microorganisms. The minimal sample size for microbiological examination was 0.2 g (mL) for synthetic substances intended for the production of non-sterile drugs and 1.2 g (mL), for sterile drugs. Based on the experimental results, a scheme has been developed for microbiological examination of particular pharmaceutical substances using a reduced sample size.

The importance of using isolation technologies, e.g., an isolator, for sterility testing of medicines is demonstrated. The advantages and disadvantages for the Sterility parameter of using isolators in manufacturing processes and pharmaceutical analysis during examination and quality control stages are discussed. The goal of the work was to optimize the chamber biological cleaning mode with a working load in a GPPI isolator (ESCO, Indonesia), which enables this equipment to be used for sterility testing of medicines. The parameters on which the success of the biodecontamination cycle of the isolator chamber depends are analyzed. Potential biological cleaning modes are studied. The optimum mode for the working load using the GPPI isolator as an example is found. The isolator system is proven to provide sterile working conditions corresponding to cleanroom class A, which makes the equipment suitable for sterility testing of medicines.

Strategies for determining particulate matter in therapeutic protein injections, including extrinsic and intrinsic particles, are reviewed. Special attention is devoted to the advantages and limitations of various methods used for these purposes, each of which enables different particle characteristics to be determined. The source of particles (extrinsic, intrinsic, or inherent) can be understood better and particle-size distribution and other characteristics can be studied and used to differentiate them if methods based on different measurement principles are used. Protein aggregates in drugs have broad particle-size distributions, from oligomers to particles reaching hundreds of microns. The particle properties can be used to assess the risk associated with protein aggregates in the drug and to study their possible formation mechanisms. Such information could be useful during drug development and manufacturing to reduce the particulate matter content.

Rapid and correct identification of microorganisms is an essential part of pharmaceutical analysis. Several phenotypic, genotypic, and proteotypic methods, each of which has its own advantages and limitations, are currently used to identify microorganisms. The aim of the present work was to reveal features and validate the operation of a Vitek 2 Compact 30 bacteriological analyzer (bioMerieux, France), which was based on determining the biochemical properties of microorganisms. The applicability of this method was determined using accuracy, precision, and robustness. Correct results were found in 86% of 396 cases. Results obtained under repeatability and intermediate precision conditions showed no differences. Approaches to molecular and genetic identification of microorganisms isolated from preparations in addition to automated biochemical identification were discussed.

Important features of the isolation of anaerobic microorganisms were examined. The detection limit and frequency and time for isolating several anaerobic bacteria by direct inoculation on thioglycollate medium and by a BacT/ALERT 3D automated system were established. Isolation of individual cells of anaerobic microorganisms with different tolerances to oxygen was shown to be possible by using thioglycollate growth medium to analyze the sterility of medicinal products. The minimum number of cells in a sample could be reliably determined in less time by using a BacT/ALERT 3D automated system and special growth medium.

The article presents general data on the chemical composition and properties of snake venoms, as well as the history of their use in medical practice. It considers the differences characteristic of the venom of snakes belonging to different systematic groups. It demonstrates that venoms remain a valuable source of new medicines. The article compares existing methods of venom analysis (immunological, chromatographic, electrophoretic, mass spectrometric). Particular attention is paid to specific metho-dological aspects of identification testing depending on the object and purpose of the analysis. The article also compares different modifications of the precipitation reaction. It highlights the advantages and disadvantages of existing methods. The affordability and simplicity of immunological methods accounts for their wide use in the analysis of poisons in biological media which helps to determine the cause of poisoning. While greater informativeness of instrumental methods makes them a perfect toll for detailed examination of poison composition during poisons research and comparison. The authors of the article performed a retrospective analysis of data obtained in identification testing of snake venoms during the period from 2006 to 2017. It has been established that manufacturer specifications for individual medicinal products in some cases do not contain instructions on the use of a specific type of precipitation reaction or the description of test procedures. It was concluded that some modifications should be made to the existing method, the choice of conditions for sample preparation should be considered, or alternative methods for identification of snake venoms in medicinal products should be developed.

The aim of the present work was to examine the applicability of an alternative method for detecting CO2 using an automated BacT/ALERT 3D colorimetric microbiological detection system and analytical parameters for sterility testing of medicinal preparations (MPs) that were selected, justified, and harmonized with leading global pharmacopoeias. The tests used microorganisms and samples of 38 MPs and compared the results with defined criteria for pharmaceutical microbiology. The experimental results showed that the alternative method did not cause discrepancies and was suitable for MPsterility testing. However, the lack of regulations for validation standard procedures in the RF currently limits replacing routine methods by alternative ones.

The article describes the use of antimicrobial preservatives in medicines for children Authors analyzed domestic and foreign regulatory documents, which establish requirements for the quality of mdications and identified the main dosage forms with preservatives. Current data about the range of antimicrobial preservatives, containing in the various dosage forms is presented.

A new approach to microbiological analysis of several pharmaceuticals, in particular, those that can be used in manufacturing sterile medical products, is presented. The proposed approach was verified using a series of 23 samples of various products, three of which were obtained by biotechnological methods. The scheme includes inoculation of samples with test strains followed by isolation and analysis of the contaminants. Validation results showed that the amount of products for microbiological analysis could be reduced to 3 g, which was sufficient for obtaining reliable results. Tryptic soy broth was used as the solvent (diluent) and enrichment broth for microbe growth.

We present an information-analytical review of methods for evaluating the sterility of solid drug formulations. Current normative documentation regulating the quality of parenteral drugs is analyzed and the main limitations of the test method for this indicator are described. The probability of detecting microorganisms depending on the proportion of contaminated units in a batch and the quantity of sample taken for analysis is assessed. Results obtained from analysis of the State Register of Drugs relating to the nomenclature of drugs in solid formulations and their areas of use are presented. The characteristics of tests for individual pharmacological groups of drugs are described.

The efficacies of the antimicrobial conservants in a number of nonsterile medicinal formulations for oral use as syrups and solutions were evaluated, i.e., Klarisens® syrup 1 mg/ml, El’kar® solution for oral use, 300 mg/ml, Lasolvan® syrup 15 mg/5 ml, and others. The quality of seven study samples containing conservants such as benzoic acid, methylparaben, propylparaben, sodium benzoate, and ethanol complied with the requirements of General Pharmacopeia Monograph OFS 42-0069-07 “Determination of the efficacy of antimicrobial conservants in medicines”. The results of the studies reported here were obtained using a modified deep plate inoculation method recommended by the State Pharmacopeia of the Russian Federation XII edition for determination of the microbiological purity of medicines. The modified deep plate method has potential for use as a supplementary method, and inclusion in the next edition of the State Pharmacopeia of the Russian Federation is recommended.

The use of compendial and alternative methods for drug sterility testing, the most important characteristic of which is the limit of detection (LOD), i.e., the minimum amount of viable microorganisms that can be found in the examined sample, is currently regulated abroad. The goal of the research was to determine experimentally and compare the LODs of microorganisms by direct inoculation and using a BacT/ALERT 3D Microbial Detection System automated bacteriological analyzer. Statistically significant differences between the results obtained by the different methods were not found.

We present here the results of validation of qualitative microbiological methods, particularly a modified method for determining the microbiological purity of medicines. The parameters required for validating qualitative microbiological methods and criteria for evaluating them were identified. Experimental data from validation studies demonstrate the value of using improved methods for determining microbiological purity using smaller sample sizes, and confirm that this is possible.

Various aspects of investigating microorganisms present in drugs are considered. Sources of contamination in nonsterile drugs are indicated. Problems related to changes in the organoleptic properties and therapeutic quality of contaminated drugs and the hazard of microorganisms for human health are analyzed. Data on the qualitative and quantitative composition of contaminant microflora isolated from various drugs are presented. Effective methods of contaminant isolation are described. Modern culture media and methods for the identification of bacteria and fungi during the microbiological quality control of drugs are presented.

Methods of evaluation of the antimicrobial activity of nonsterile medicinal preparations are considered. A modified method according to the State Pharmacopoeia (XIth Ed.) is compared to an alternative replication technique applicable to water-insoluble products and also to fatty and colored preparations. The replication method has the advantage of being economical (use of only two culture media), fast (24 – 72 h), and universal (admitting the use of a broad set of test microbes). The final choice of the method depends primarily on the nature of each particular preparation.

Ready-to-use medicinal preparations and related auxiliary substances were inoculated with yeast and mold fungi, and their dynamics was monitored over a period of time up to several months. During the period of observation, the amount of some fungi decreased, provided that the conditions of storage excluded elevated humidity. Each case of drug contamination on storage must be thoroughly considered taking into account the nature of each particular preparation, the amount and species of fungi, and the duration and conditions of storage.

The appearance of precipitates and opalescent components hinders testing for the sterility of insulin suspensions by seeding in cultural media. The sampling procedure is improved by dissolving preparations in 0.2% aqueous ascorbic acid solution, which eliminates opalescence and precipitation and facilitates the reading and interpretation of the test results as the test solutions become transparent. This method is suitable with both direct inoculation and membrane filtration. The insulin solution in 0.2% ascorbic acid does not exhibit antimicrobial activity, which makes expedient testing with the more economical direct inoculation.