Biologically active sulfur-containing compounds (BASC) exhibit pronounced antioxidant properties. Glutathione reduced (GSH) occupies a particular position among these compounds. It represents a key link in the 3 antioxidant systems of the body from the existing four. Based on the foregoing, a GSH-based dosage form with antioxidant properties was proposed. The aim of this study is to work out a model granulated dosage form based on GSH and methods of its analysis by means of pre-column derivatization with ortho-phthalic aldehyde.Materials and methods.GSH and granulated dosage form based on GSH obtained by wet granulation were used as the object of the study. Quantitative evaluation of GSH content in the obtained granules was carried out using pre-column derivatization by the method of reversed-phase high-performance chromatography (RP HPLC). Ortho-phthalic aldehyde was used as a derivatizing agent. A diode-array detector was used to detect the resulting derivative. Ortho-phthalic aldehyde was used as a derivatizing agent. A diode-matrix detector was used to find out the resulting derivative.Results.In the course of the work, a model dosage form was created – granules based on GSH. By reference to the recommendations on the dosage of the drug, the concentration of the active substance was selected. Lactose was chosen as an auxiliary component. Physical and technological characteristics of a model sample of granules with GSH and lactose as a filler were studied. A method of quantitative determination of GSH in granules using pre-column derivatization with ortho-phthalic aldehyde was developed and validated by HPLC. The method of quantitative determination of GSH in granules with the use of pre-column derivatization by ortho-phthalic aldehyde by HPLC was developed and validated.Conclusion.The developed granulated dosage form meets the requirements given in the pharmacopoeial item “Granules” according to the analyzed indicators. Using the validation evaluation it was established, that the developed methods for the quantitative determination of GSH in granules is correct, precise and specific.

The aim . This article is devoted to the intensification of the production process of a thick extract of milk thistle fruits using ultrasonic processing of raw materials. Materials and methods. As an object of the study, the crushed milk thistle fruitss from Penza “Biokor” company were used. As the extractant, an aqueous solution of ethanol 70% vol. was used. For ultrasonic processing of plant materials and extractant, the installation “Bandelin SONOPULS HD 3200” was used, the ultrasound frequency was 20 kHz, the radiator power was 280 W, and the temperature was 25°С. The concentration of the extract was performed using a rotary evaporator RV-10 at the temperature of 60°C and a vacuum of 600–650 Mmhg to a residual moisture content of 25%. Qualitative and quantitative analysis of the thick extract was carried out using spectrophotometry and chromatography. Quantitative analysis of the amount of flavolignans was performed on an SF-56 spectrophotometer. The separation of the flavolignan complex and the quantification of silibinin was performed on a liquid chromatograph “Agilent Technologies 1200 Infinity”. Results and discussion . During the study it was found out, that processing of the crushed milk thistle fruits by ultrasound at the soaking stage almost doubles the output of the flavoligan complex from medicinal plant materials. The maximum amount of flavolignans is extracted when the fruits of milk thistle and extractant are processed with ultrasound at the frequency of 20 kHz for 5 minutes. Thus the obtained thick extract of milk thistle fruits in the component composition contains both the target flavolignan complex (87.39%, silibinin – 24.36%), providing the hepatoprotective effect, and flavonoids – chlorogenic acid (1.69%) and dihydroquercetin (10.92%) exhibiting antioxidant activity. It was established that, according to the qualitative composition of flavolignans, the obtained thick extract corresponds to preparations based on milk thistle. Thus, for the first time, the method was proposed for obtaining a thick extract of milk thistle fruits using ultrasonic processing of raw materials and extractant at the soaking stage. The obtained thick extract is proposed to be used as an active pharmaceutical substance for the production of granules based on methionine and milk thistle flavolignans. Conclusion . The results of the experiments allow us to recommend obtaining a thick extract of the milk thistle fruits, using the stage of ultrasonic processing of raw materials and extractant for 5 minutes at the ultrasound frequency of 20 kHz.