Целью настоящей работы является оценка эффективности снижения токсичности лекарственного средства (ЛС) группы противовирусных препаратов- Рибавирин. Для этого был применён оригинальный метод биотестирования Spirotox в сочетании с модельной схемой ферментативной кинетики Михаэлиса-Ментен. Для снижения токсичности, в качестве среды растворения использовали природный комплекс гуминово-фульвовых кислот (ГК). Показано, что разведение ЛС комплексом гуминово-фульвовых кислот способствует увеличение времени жизни клеточного биосенсора по сравнению с водой очищенной Рассчитанные кинетические параметры уравнения Михаэлиса-Ментен для водных растворов Рибавирина fm=18,2 с ; Кр=2,5 · 10 моль/л и с использованием в качестве разбавителя ГК : воду очищенную (140-145 ppm) fm=1,0 с ;Кр=0,3 · 10 моль/л демонстрирует способность ГК снижать токсичность противовирусных ЛС.

Introduction . The strategy of quality control of drugs provides for compliance with the requirements of regulatory documentation methods and critical quality indicators that determine its effectiveness. Special attention should be paid to the properties of the initial pharmaceutical substance (lipophilicity logP, area of the topological polar surface of TPSA, particle size, polymorphism), which determine the solubility and dissolution rate of the active pharmaceutical substance (APS) in terms of their impact on the bioavailability of the finished drug in vivo  [1–3]. Since the assessment of pharmacopoeia solubility of APS is reduced to a visual procedure and the use of approximate terms, we have developed an original method for determining the dissolution rate of substances using the laws of chemical kinetics. Validation of the analytical method is carried out at introduction of the new method, and also at change of conditions of analysis of medicines carried out during the life cycle (product lifecycle) of a pharmaceutical product and its manufacturing process [4]. The proposed technique for laser determination of the dissolution rate in water of a medicinal substance of fluoroquinolone group has been tested; elements have been included in validation studies: repeatability, precision, linearity and range. Aim . Development of the method for determining the dissolution rate of active pharmaceutical substances by laser light diffraction with validation elements. Materials and methods . Determination of the dissolution rate of moxifloxacin hydrochloride was carried out in water for laboratory analysis of purity level 1 (ultra-pure water) obtained on the Milli-Q ® Integral, the quality of which corresponds to ISO 3696:1987. To achieve this goal, a pharmacopoeia method of research was used – low-angle scattering of laser light (laser diffraction method); instrument equipment – laser dispersion meter Malvern 3600 EC. Results and discussion . An additional analytical method for determination of API dissolution rate by laser light diffraction method was developed. Validation studies on parameters: precision (repeatability, intra-laboratory/intermediate), linearity, analytical region. Precision was estimated based on the results of 18 measurements, the coefficient of variation was 8 %, the relative error of average 4 %. Linearity was determined (correlation coefficient R = 0.992). The range of application of the analytical technique depends on its purpose, is determined in the linearity analysis and ranges from 5 · 10 -3 g/ml to 5 · 10 -2 g/ml. Conclusion . The proposed methodology can be used as an independent test of the properties of pharmaceutical substances both at the stage of their development and preclinical studies, and in the process of quality control in addition to the existing pharmacopoeia test to assess the solubility of pharmaceutical substances, expressed in terms of conditional.

Solubility is the most important quality indicator, reflecting the physicochemical properties of active pharmaceutical ingredients (APIs). Prior to the release of API, solubility is one of the key factors affecting the efficacy and safety of drugs. Therefore, the directed development of new drugs with predetermined properties (drug design) should be basedon solubility of candidate substances and be taken into account when evaluating the bioequivalence of generic drugs branded, including in vitro - in vivo correlation. Given that the pharmacopeia regulation of the test for the solubility of API is reduced to a visual estimate and approximate solubility, we developed a kinetic dissolution evaluation method by laser diffraction and performed statistical analysis of the results obtained under repeatability conditions.

The kinetic evaluation of solubility of drug substances of different chemical and pharmacological groups (bendazol hydrochloride, lactose monohydrate and taurine) was conducted in aqueous solutions with different isotopic composition of hydrogen. The choice of solvent was made due to the fact that the replacement of purified water, containing 141,0 ± 0,9 ррm 2 1 H(D ) heavy isotope of hydrogen, to water with low content of 2 1 H(D ) can accelerate the solubility of the active process pharmaceutical ingredients (APIs), approximately in 1,5 times. The study was carried out by the laser light diffraction method, which is the basis of the Monograph.1.2.1.0008.15 SF RF XIII «Particle size distribution». In contrast to the existing methods of the pharmacopoeial analysis governing the visual assessment of the completeness of the solubility of the API, the laser diffraction method allows to get an objective assessment of the solubility of the API based on the change of the integral characteristics of dispersion over time.

Drug release studies (or in vitro release) of valsartan in three dissolution media simulating the main sections of the gastrointestinal tract were conducted. The concentrations were determined using UV/Vis spectrophotometer (Varian Cary 50) at 254 nm. The study was conducted using dissolution apparatus with the paddle assemble; 5-mL sample aliquots were withdrawn at 5, 10, 15, and 30 min. Estimation f2 parameter confirmed the equivalence of valsartan dissolution kinetics: f2=67 in hydrochloric acid solution, pH 1,2; f2=57 in phosphate buffer, pH 4,5, and in phosphate buffer, pH 6,8 - dissolution amount is greater than 85% at 15 min, so the two products are deemed equivalent, and a profile comparison is not necessary.

Two optical methods - polarimetry and laser light diffraction - have been used to study valine aqueous solutions. It has been shown that optical activity of valine enantiomers depends on deuterium content in aqueous solutions. The influence of deuterium-dependant heterophase clusters of water on optical activity of valine aqueous solutions has been discussed.

В последнее время значительно возросло число биотехнологических препаратов на основе гликопротеинов и хиральных лекарств, полученных органическим синтезом. Особенности гликозилирования белка, которые могут быть обусловлены таутомерными превращениями углеводов, влияют на механизмы действия, фармакокинетику, фармакодинамику, устойчивость и иммунные свойства лекарственных средств. Продолжающаяся дискуссия о необходимости разделения активного и его инертного/токсичного оптического антипода органического соединения стимулирует поиск новых методов контроля качества оптически активных лекарственных средств. В работе приведены результаты исследования кинетики мутаротации D- и L-галактозы в водных растворах с различной мольной долей тяжелого изотопа водорода — дейтерия.

В настоящей работе методом биологического тестирования на клеточной культуре (модель SpiroTox) в водных растворах разного изотопного состава и термическим анализом твердофазных субстанций исследовано взаимодействие вспомогательного вещества класса антиоксидантов — натрия сульфита — и фармацевтической субстанции 3-гидрокси-6-метил-2-этилпиридина гидрохлорида.

Stationary stability of giant heterophase clusters (GHCs) of water in samples of sodium chloride isotonic aqueous solutions from, three manufacturers has been studied. The influence of the NaCl concentration on the relaxation kinetics of GHCs is established. A method for determining the identity of aqueous drug solutions without violating the integrity of packaging is developed.

A series of barium sulfate samples from different manufacturers have been studied by means of dispersive analysis using small-angle laser radiation scattering (SALS) technique. The presence of particles with sizes exceeding 10 μm (i.e., beyond the allowed range) is established. Based on the obtained results, it is possible to recommend the SALS method for rapid dispersive analysis of drug powders and suspensions.

Modern approaches to definition of properties and qualities of the natural water intended for manufacturing of pharmaceutical preparations are considered. It is shown, that waters of the internal seas render toxic influence on a cellular biosensor control that is connected with significant anthropogenous loading on them. The analysis of water supramolecular structure can serve the express train-estimation of quality of suitability of water for application in the medical purposes.

The new developments of the department of pharmaceutical and toxicological chemistry (RPFU, Medical faculty) in the field of heterogeneous, system (suspensions^ emulsions, aerosols and powders) investigations with low angle laser light scattering and laser interferometry are observed and described.