Получение водорастворимых сополимеров n-винилпирролидона и n-оксида 2-метил-5-винилпиридина и исследование их иммуноадъювантной активности

In this work partially and completely N-oxidized N-vinylpyrrolidone-2-methyl-5-vinylpyridine copolymers were synthesized. The influence of рН on the reaction course was studied. For obtaining the copolymer N-oxidized by 100% it is necessary to carry out the reaction in an acetate buffer solution. If obtaining the partially N-oxidized copolymer, a citrate buffer solution should be used, which allows carrying out the reaction at a smaller speed and as a result enables to stop the reaction in the necessary range. The dependence of biological activity on the extent of N-oxidation was studied. An immunostimulating effect of N-vinylpyrrolidone-2-methyl-5-vinylpyridine N-oxide copolymers with various extent of N-oxidation was revealed in vivo with an anthrax vaccine.Синтезированы частично и полностью N-оксидированные сополимеры N-винилпирролидона и 2-метил-5-винилпиридина. Выявлено влияние рН среды на протекание реакции N-оксидирования. Проведены биологические испытания полученных субстанций

Разработка метода получения полимерных микросфер, содержащих иммобилизованный диклофенак

The dependence of characteristics of microspheres and the kinetics of drug release from the particles on the type and intensity of mechanical action on the emulsion upon the preparation of polymeric microspheres containing encapsulated diclofenac based on a copolymer of lactic and glycolic acids was investigated. According to the results of the research conditions were selected for the production of microspheres with the gradual release of drug from the particles during two weeks. The polymer microspheres are promising for further study and creation of prolonged dosage forms of diclofenac on their basis.На основании проведенных исследований предложен метод получения полимерных микросфер с иммобилизованным диклофенаком. Разработанная методология иммобилизации диклофенака позволила получить полимерные микросферы с характеристиками, обеспечивающими пролонгированное высвобождение лекарственного вещества из полимерной матрицы

Разработка и валидация метода количественного определения диклофенака в полимерных микросферах

This article describes a new method of determining concentration of active ingredient in diclofenac-loaded polymer microspheres by using HPLC analysis. Proposed method showed better repeatability than more commonly used UV-Vis spectrometry. Isocratic liquid chromatograph with Luna C18 (2) Phenomenex column and UV detector (254 nm) was employed. Various parameters, such as specificity, repeatability, limit of quantification and stability, were measured to validate the method. Chromatogram showed only diclofenac-related peaks, which means specificity was adequate. Recovery was determined using 5 standard diclofenac solutions with known concentration. Repeatability and reproducibility were calculated based on data from two series of microspheres. LOQ was found using standard curve. Stability was observed during 30 days since sample preparation. Based on these results, suggested method successfully passed the validation process and can be used for quality control of diclofenac-loaded microspheres.В статье предложена новая методология количественного определения диклофенака в виде свободной кислоты, инкапсулированного в полимерный носитель, позволившая повысить точность определения содержания лекарственного вещества

Preparing water-soluble n-vinylpyrrolidone-2-methyl-5-vinylpyridine n-oxide copolymers and research on their immunoadjuvant activity

In this work partially and completely N-oxidized N-vinylpyrrolidone-2-methyl-5-vinylpyridine copolymers were synthesized. The influence of рН on the reaction course was studied. For obtaining the copolymer N-oxidized by 100% it is necessary to carry out the reaction in an acetate buffer solution. If obtaining the partially N-oxidized copolymer, a citrate buffer solution should be used, which allows carrying out the reaction at a smaller speed and as a result enables to stop the reaction in the necessary range. The dependence of biological activity on the extent of N-oxidation was studied. An immunostimulating effect of N-vinylpyrrolidone-2-methyl-5-vinylpyridine N-oxide copolymers with various extent of N-oxidation was revealed in vivo with an anthrax vaccine

Quantitative Determination of Benzalconium Chloride in the Naltrexone Hydrochloride Nasal Spray

Introduction. Benzalkonium chloride is widely used as a conservation agent in medicines. For quantitative determination, the methods described in the European and American Pharmacopoeias by chromatography using columns with nitrile sorbent are often used. However, in order to unify the methods and simplify the quality control technology in the production process, it is advisable to adapt the existing methods for new goals and objectives.Aim. To develop a method for the quantitative determination of benzalkonium chloride in a nasal spray containing a thermosensitive polymer Poloxamer 407 and validate it.Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. The quantitative determination of naltrexone in the test sample was developed using a Dionex UltiMate 3000 high-performance liquid chromatograph (Thermo Fisher Scientific, USA) equipped with a diode-matrix detector.Results and discussion. The paper explored the possibility of using an earlier developed method for the quantitative determination of naltrexone hydrochloride for the quantitative determination of benzalkonium chloride in the composition of a nasal spray. Based on the results obtained, changes were made to the quantitative determination method, and the sample preparation of the samples under study was adapted.Conclusion. As a result of the studies carried out, the most acceptable conditions for the preparation of the nasal spray for the quantitative determination of the preservative were selected. The developed technique provides for the chromatographic conditions previously used for the determination of naltrexone hydrochloride, which makes it possible to use the equipment as efficiently as possible in the analysis of the finished drug. The method has been validated and its specificity, linearity, correctness and precision have been proven

Quantitative Determination of Naltrexone Hydrochloride in a Nasal Spray by High-performance Liquid Chromatography

Introduction. Naltrexone, an antagonist of µ-opioid receptors, is promising for the treatment of various autoimmune and oncological diseases when used in doses of 1.5–5 mg/day. To date, there are no medications that provide such dosages of naltrexone.Aim. Development and validation of a method for the quantitative determination of naltrexone hydrochloride in a nasal spray by high performance liquid chromatography (HPLC).Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. The quantitative determination of naltrexone in the test sample was developed using a Dionex UltiMate 3000 high-performance liquid chromatograph (Thermo Scientific, USA) equipped with a diode-matrix detector.Results and discussion. The possibility of using isocratic and gradient chromatographic modes for the quantitative determination of naltrexone hydrochloride in the nasal spray was studied. Based on these results, a new method of determination using the gradient mode is proposed, which allows minimizing the influence of the polymer component in the test sample on the analysis results.Conclusion. A new technique of high-performance liquid chromatography (HPLC) is proposed that allows identification and quantification of naltrexone hydrochloride in a nasal spray containing a high concentration of water-soluble heat-sensitive poloxamer as a thickener. The developed method was validated according to the parameters: correctness, precision, specificity, linearity

Development of a method for preparing polymer microspheres containing immobilized diclofenac

The dependence of characteristics of microspheres and the kinetics of drug release from the particles on the type and intensity of mechanical action on the emulsion upon the preparation of polymeric microspheres containing encapsulated diclofenac based on a copolymer of lactic and glycolic acids was investigated. According to the results of the research conditions were selected for the production of microspheres with the gradual release of drug from the particles during two weeks. The polymer microspheres are promising for further study and creation of prolonged dosage forms of diclofenac on their basis

IMMUNOADJUVANTS, ITS CLASSIFICATION AND APPLICATION IN PHARMACEUTICAL INDUSTRY

The present review is devoted to the investigation of immunoadjuvants. The main properties of adjuvants, their species and reasons of the use in vaccines are considered. Adjuvant classification is described

Elaboration and validation of method of quantitative determination of diclofenac in polymeric microspheres

This article describes a new method of determining concentration of active ingredient in diclofenac-loaded polymer microspheres by using HPLC analysis. Proposed method showed better repeatability than more commonly used UV-Vis spectrometry. Isocratic liquid chromatograph with Luna C18 (2) Phenomenex column and UV detector (254 nm) was employed. Various parameters, such as specificity, repeatability, limit of quantification and stability, were measured to validate the method. Chromatogram showed only diclofenac-related peaks, which means specificity was adequate. Recovery was determined using 5 standard diclofenac solutions with known concentration. Repeatability and reproducibility were calculated based on data from two series of microspheres. LOQ was found using standard curve. Stability was observed during 30 days since sample preparation. Based on these results, suggested method successfully passed the validation process and can be used for quality control of diclofenac-loaded microspheres

STANDARDIZATION OF CATIONIC DERIVATIVE OF BAKTERIOPURPURINIMID AS PHARMACEUTICAL SUBSTANCE FOR ANTIMICROBIAL PHOTODYNAMIC THERAPYA

In this paper key indicators due to Pharmacopoeia XIII [1] that can be used to standardize the cationic derivative of bakteriopurpurinimid as pharmaceutical substance (PS) are presented. The prime application of this compound to be a photosensitiser for antimicrobial photodynamic therapy (PDT)