In article we analyse key practical aspects of contract manufacturing agreements with respect to pharmaceuticals in Russia.

In article theoretical and practical results of longstanding work of collective of Pharmaceutical technology department of Kursk State Medical University for the development of rectal and vaginal suppositories for the treatment of infectious and inflammatory diseases have been shown and approaches to the choice of rational suppositories composition and technology, including using of Dissolution test, have been formulated.

Rheological characteristics of the original basis tizol gel and medicinal compositions on this basis were studied by method of viscosimetry, constructed and analyzed curves of viscosity and flow curves objects of research, calculated their mechanical stability. It was shown that the medicinal compositions made on the basis of tizol gel have optimal structural and mechanical properties which the soft medicinal form for local and external application has to possess. Expediency and efficiency of application of this basis for production of medicinal compositions in manual recipes were confirmed.

The work is devoted to the development of novel ophthalmic drug prolonged action in the treatment of cataract of different genesis, degeneration and corneal injury. The results showed the possibility of creating an ophthalmic gel based on carbomers with the addition taurine. The resulting preparation was studied on the basic parameters that demand for ophthalmic dosage forms.

With this study the results of influence particle size distribution and method of modification API on dissolution profile from matrix tablets with sustained release are shown. The effect of Hydroxyethylcellulose, which is used as sustained release agent, also as an excipient, able to improve dissolution speed and maintain more complete release of an API from sustained release formulation, with glibenclamide as an example has been studied.

There were illustrated the main questions of development of new generation drug delivery systems as hybrid nanomaterials as follows: selection of nanocarrier, its standardization and the methods of immobilization of biologically active and medicinal substances. The basic organs of distribution and accumulation of advanced carbon nanocarrier - detonation nanodiamond were identified. It was shown that antihypoxic effect of the nanodiamond-glycine conjugate increased in comparison with a native Glycine and Mexidolum® as reference drugs.

In the review describes the main properties of cyclodextrins and their potential use in the formulations in various dosage forms as excipients, by which it becomes possible to modify the solubility of drugs, increase the bioavailability and stability of the drug.

This article has described some of the ways in which the delivery of an active ingredients, in terms of there rate of permeation and location within the skin, can be controlled through formulation design. Every ingredient in the formulation possesses the potential to have some effect on the delivery of an active ingredient, either through its effect on the solubility of the active, its interaction with the skin, or on the formulation as it undergoes various phase changes on the skin. It is therefore important to consider the role of every ingredient in the formulation to optimize a delivery of the active ingredient.

The quality review procedure, which is an essential improvement of the quality system by manufacturers, was used for monitoring the stability of the production process and quality of Ambroxol syrup. The quality review of Ambroxol syrup was carried out, using Shewhart’s control charts. Reproducibility and stability of the manufacturing process of the drug product were evaluated with respect to a set of parameters.

The development of the biopharmaceuticals begins with the development of effective producers. But the more complex protein and its producer, the greater the amount of impurities is synthesized or accumulated during the upstream process. Among them are as follows: bacterial endotoxins, viruses, host cell proteins, related impurities, aggregates and high molecular weight admixtures etc. This article describes approaches to the downstream process purification of biopharmaceutical proteins. We discuss the main chromatography and non-chromatographical methods.

On the base of the experimental studies of some magnetic medications and dosage forms, magnetic fillers for magnetic dosage forms (by means of chemical, physical-chemical, physical methods) the experimental tests of the quality control of finely-dispersed magnetite, finely-dispersed barium ferrite have been developed.

The possibility of the use of chromatographic columns with amino sorbents for the analysis of nitroglycerin and separation of isosorbide dinitrate and isomers of isosorbide mononitrate was investigated. As the mobile phase used a mixture of acetonitrile and water. Separation of analytes on amino columns in condition of the hydrophilic interaction liquid chromatography possible with acetonitrile content in the mobile phase, more 95%. Best separation isomers of isosorbide mononitrate on column Zorbax NH₂, 150×4,6 mm was achieved with acetonitrile content in the mobile phase 99,8%. Separation of isosobide dinitrate and isosorbide mononitrates on columns with amino sorbents resulted in changing the sequence of elution of these compounds compared to reversed-phase chromatography.

This paper considers the possibility to comprehensive quantification of pyridoxine hydrochloride, thiamine hydrochloride, cyanocobalamin, lidocaine hydrochloride, benzyl alcohol are selected of “Vitagamma solution for intramuscular injection in ampoules of 2 ml per pack №5×2” drug by HPLC method. The expediency of using 0.1 M sodium orthophosphate solution with pH level equal to 5 as a buffer solution and introduction of 0.001 M sodium pentansulfonat as an ion pair agent is proved. The conditions for chromatographic determination of active ingredients in the drug are selected: a gradient of concentration of the organic solvent (acetonitrile) from 2 to 60%; chromatographic column ZORBAX Eclipse Plus C8, 3.0×150 mm, 3.5-Micron; column temperature 30 °C; mobile phase velocity of 0.6 ml/min; spectrophotometric detector wavelength of 245 nm; sample volume of 20 ul.

The main objectives of stress experiments and tests corresponding to them, and also stress experiments for preparation of solutions for check of system suitability of chromatographic systems are in detail considered. Approach for systematization and the analysis of results of stress experiments (stress testing) is offered. This approach is based on use of relative times of peaks of substances and on the special table, which allows resolving overlapping peaks before and after stress tests with high confidence; it is especially important for development and validation of the analytical methods. The table also gives the possibility to correlate peaks of impurity to certain types of negative chemical reactions of decomposition/transformation of drug substances. Recommendations are presented for conducting stress tests, which would be without doubts a great help in practice.

The simple and available technique of determination of tetracycline in the form of colored complex with iron(III) ions and B₁₂ vitamin in the form of the colored thiocyanate complex of cobalt(II) after a chemical mineralization of cyanocobalamin is offered. The analytes were separated from the accompanying components by sorption to polyurethane foam based on ethers. The conditions of sorption separation and measurement of analytical signal of these substances are optimized. The obtained results are in satisfactory agreement with data declared by the manufacturer. The adequacy of proposed approach is confirmed by results of indirect X-ray fluorescence analysis of tetracycline drug substance and injection solution B₁₂ vitamin (cyanocobalamin).

Abnormal Toxicity test is obligatory in the Russian Federation for standardisation of biological origin substances, despite an ambiguous assessment of its expediency. Evaluation of abnormal toxicity of insulin by a standard technique is impossible because its introduction causes death of animals as a result of hypoglycemic shock. A change in pharmacopoeial technique defines need of its validation. On the example of substance of human genetically engineered insulin Rosinsulin (LLC «Zavod Medsintez») with mice males as biological test system the optimum conditions of the test were proposed. They include intraperitoneal introduction of glucose solution in 60 min, prior to intravenous administration of insulin. Indicators of intoxication, body weight and blood glucose level were monitored during the test for three bathes of insulin substance. Abnormal Toxicity test was validated on Robutness (with influence of small changes of volume of the entered solution of insulin and time between introduction of glucose and insulin solutions) and a Precision (intra-day and inter-day). Satisfactory results for all validation parameters were received.

Results of development of differential spectrophotometry method for determination of the total flavonoids assay in tablets containing dry extracts of ginkgo biloba are presented. Total flavonoid assay in leaves of ginkgo biloba and grass meadowsweet is preliminary presented by LLC «Vitaukt-Prom». The assay method for the sum of flavonoids in the dry extracts from this raw material and tablets «Ginkgotropil-forte» is developed. Justification of limit of flavonoid content in tablets «Ginkgotropil-forte» is presented and the limit is not less than 6 mg, based on the average weight of the tablet. The proposed method was validated for specificity, linearity, precision and accuracy.

This article describes the results of the development of composition and technology of a combined drug, containing lercanidipine and ramipril, affording equivalent dissolution kinetics with original drugs. The comparative release profiles of the active pharmaceutical ingredients are shown. The choice of a solid dosage form in the form of bi-layer tablets was substantiated.

Dissolution profile study for extended-release valproic acid preparations was performed in three dissolution media: 0.1 M hydrochloric acid, acetate buffer pH 4.5, citrate-phosphate buffer pH 6.8 using Apparatus 1 at 75 rpm. Time points were 1, 2, 3, 4, and 6 hours. Assay of released API was performed using HPLC-UV. API did not released or slightly released in 0.1 M hydrochloric acid and acetate buffer pH 4.5 because of low solubility of valproate in acid form. Recommended dissolution medium was citrate-phosphate buffer pH 6.8 which provides high solubility, stability and complete release of API.

Pre-clinical studies in Russia are required to be compliant with the Ministry of Health of Russia order N 708 «On approval of the rules of laboratory practice". One of the most important aspects of the quality of carried out research is possibility to reconstruct the study after its completion on the basis of archived materials. Order of Ministry of Health of Russia issued on 06.06.2013 N354n "On the procedure of autopsy" requires storage of biological materials in 10% formalin solution before the end of the histological study and also storage of micropreparations and paraffin blocks for3 years. Our study identifies and describes the most frequently encountered artificial changes that occur in the archived material with the passage of time in compliance with the recommendations on storage conditions.

The pharmacological activity of the combined formulation including ethanol-induced narcosis was studied. It is shown that the daily use of the combined formulation on the background of subchronic alcohol intoxication prevents the development of resistance to ethanol and reduces ethanol-induced narcosis both at single and prolonged administration.

Study of main CYP isoforms activity using «cocktail» method was conducted on patients suffered from drug allergy with different concurrent diseases in order to determine the presence of correlation between drug allergy appearance and changes in biotransformation activity.

A new method for determination of moxifloxacin in human plasma using HPLC with UV-detection is described. The sample preparation was made by protein precipitation by 50% trifluoracetic acid solution. The method was validated in terms of selectivity, calibration curve, accuracy, precision, lower limit of quantification, carry-over and stability. The analytical range was 100-5000 ng/mL. Limit of determination was 31 ng/mL. Method could be applied to moxifloxacin determination in plasma for PK and BE studies.

Some aspects of the adequate use of reference standards (RS) for making a reliable decision on the compliance of medicines are reviewed. An analysis of the specificity of using RS with the certified value and substance/reagent, for which the nominal value is considered to be 100%, is conducted. Status and specific character of using pharmacopoeial RS are considered. Issues of the use of RS for non-pharmacopoeial test methods as well as for non-pharmacopoeial medicines, problems of provision of RS for purity tests and RS for the analysis of herbal drugs and herbal drug preparations are analyzed. Some metrological aspects of the proper use of RS related to the implementation of the concept of uncertainty and the use of the principle of insignificance are discussed.

In this article the current state of the legal regulation of age restriction for using of medicines in children in Russian Federation has been analyzed. The ways for addressing legal uncertainties between the register of the standard labels of the interchangeable medicines and labels of concrete medicines, approved at their state registration, have been offered. The necessity of development of the list of data for compulsory including in the register of the standard labels of the interchangeable medicines have been proved. The prospects of the using of the register of the standard labels of the interchangeable medicines to improve of drug supply of pediatric patients have been studied.

The principles of the rational pharmacotherapy in pediatric practice are generalized. It should take into account characteristics of pharmacokinetic and pharmacodynamic of drugs influences on the children organism. It is established, that solution of problem for development of high-potent and harmless pharmaceutical forms for children is impossible without including medical, pharmaceutical and regulatory aspects.

The regulatory requirements are constantly increasing in the medicines manufacturing sphere, which is reflected in the good manufacturing practice rules. The changes in the GMP regulations relating to personnel, premises and equipment, production, quality control, complaints, quality defects and product recalls, as well as a new version of qualification and validation annex and certification by a Qualified Person and batch release annex have been characterized and analyzed in a review. The related information sources have also been analyzed in order to facilitate the interpretation and implementation of these innovations in the practice of company-producers and, in the long term, the work of the regulatory authorities. The review provides recommendations on the priorities and points of application of efforts to implement the changes discussed.

The paper presents the literature data on the knowledge K. Galen in pharmacology. The source of information is the materials published in domestic and foreign literature.