Development of Effervescent Granules with Solid Dispersion of Furazolidone

Introduction.In the treatment of infectious and inflammatory diseases, active substances (AI) are in demand, characterized by low resistance of microorganisms, high specificity of the mechanism of action and a wide spectrum of antimicrobial activity. Furazolidone (FZ) is an active substance that meets these criteria, but the fact that it is practically insoluble in water significantly limits its use. To increase the solubility and dissolution rate of active substances with low solubility in water, the method of solid dispersions (SD) allows. Previous studies indicate an increase in the solubility and dissolution rate of FZ in water from TD with polyvinylpyrrolidone-24000 (PVP-24000) in a ratio with AI > 6: 1 by weight. As a result, it becomes possible to introduce TD FZ into the composition of instant effervescent dosage forms, for example, Target. Development of the composition and technology for obtaining effervescent granules based on solid dispersions of FZ for obtaining a solution for external use. Materials and methods. FZ substance, polyvinylpyrrolidone-24000 ± 2000 (PVP-24000 ± 2000), tartaric acid, malic acid, anhydrous sodium carbonate, ethyl alcohol 96%, purified water. The granulates were obtained by fluidized bed granulation. The analysis of the obtained granules was carried out according to the following indicators: Description, granule size, weight loss upon drying, disintegration, dosing uniformity according to GPM.1.4.1.0004.15 "Granules". Also carried out a qualitative and quantitative determination of DI, analyzed the pH of an aqueous solution of granules. In order to study the stability and shelf life, the samples of granules were stored in accordance with OFS.1.10009.15 "Stability and shelf life of medicines".Results and discussion. The composition and technology of FZ effervescent granules for obtaining a solution for external use have been developed. The granules were obtained by separate granulation of the main (containing TD DV) and acidic components, followed by mixing in proportions that provide a solution of FZ with a concentration of 0.004% in water at room temperature. The quality of the resulting compositions was assessed, the shelf life (2 years) and storage conditions (in a dry place protected from light at a temperature of 25 °C) of the developed granule compositions were determined. Conclusion. As a result of technological and chemical-pharmaceutical studies using the TD method, a new dosage form of FZ has been developed - effervescent granules, which makes it possible to obtain an aqueous solution with an AI concentration of 0.004% in less than 5 minutes without heating. Based on the results of the work, an application was filed with Rospatent No. 2021105988 dated March 10, 2021 "Instantly soluble dosage form of furazolidone and a method for its preparation.". © Elagina A. O., Beliatskaya A. V., Krasnyuk (Jr.) I. I., Krasnyuk I. I., Stepanova O. I., Vorob'yov A. N., Fateeva T. V., 2022

ИЗУЧЕНИЕ РАСТВОРИМОСТИ КЕТОПРОФЕНА ИЗ ТВЕРДЫХ ДИСПЕРСИЙ С ПОЛИВИНИЛПИРРОЛИДОНОМ

The effect of solid dispersions (SD) on the solubility of ketoprofen was determined. We investigated ketoprofen and its SD with polyvinylpyrrolidone (PVP) -10,000, -12600 and -24000. The preparation of SD increases the solubility and dissolution rate of a non-steroidal anti-inflammatory agent. The solubility of Ketoprofen from SD increases by 1,5-2,6 times. Dissolution rate of SD increases by 1,5-3,2 times. The complex of physicochemical methods of investigation suggests that an improvement in the release of ketoprofen from SD occurs through the preparation of a solid solution of the active substance in the polymer, the formation of intermolecular hydrogen bonds of SD and PVP, and with the solubilizing effect of the polymer upon dissolution of ketoprofen. The results can be used in the development of rapidly soluble solid dosage forms of ketoprofen with increased bioavailability.Изучена растворимость кетопрофена (нестероидного противовоспалительного средства) из твердых дисперсий на основе поливинилпирролидона (ПВП-10000, ПВП-12600 и ПВП-24000). Использование ТД повышает растворимость и скорость растворения. Растворимость кетопрофена из ТД увеличивается в 1,5-2,6 раза. Скорость растворения из ТД повышается в 1,5-3,2 раза. Исследования, проведенные комплексом физико-химических методов, позволяют предположить, что улучшение высвобождения кетопрофена из ТД происходит за счет получения твердого раствора действующего вещества в полимере, образования межмолекулярных водородных связей действующего вещества с поливинилпирролидоном и солюбилизирующего действия полимера при растворении кетопрофена. Полученные результаты могут быть использованы при разработке быстрорастворимых твердых лекарственных форм кетопрофена с повышенной биодоступностью

Антимикробная активность нитрофурала в различных лекарственных формах

Comparative evaluation of the antimicrobial activity of nitrofural based preparations by agar-well diffusion method was carried out. Diameters of the growth inhibition zones caused by nitrofural gels and solutions of solid nitrofural dispersion with 0.02 and 0.04% concentrations, as well as ointment with the active substance content 0.2% were measured. Staphylococcus aureus, S. epidermidis and Escherichia coli were used as the test strains. On the basis of obtained experimental data, it has been concluded that the antimicrobial activity of drugs containing solid dispersion of nitrofural is significantly higher than the activity of drugs commercially available on the market at present.Проведена сравнительная оценка антимикробной активности препаратов нитрофурала методом диффузии в агар. Определены зоны задержки роста микроорганизмов под действием гелей и растворов, содержащих твердую дисперсию нитрофурала с концентрацией действующего вещества 0,02 и 0,04 %, а также фурацилиновой мази 0,2 %. В качестве тест-штаммов использовали: Staphylococcus aureus, Staphylococcus epidermidis и Escherichia coli. На основании полученных экспериментальных данных сделан вывод о более высокой антимикробной активности препаратов, содержащих твердую дисперсию нитрофурала, по сравнению с препаратами, представленными на фармацевтическом рынке