2025, №3

сс. 42-49

Study of the Effect of Micronization of N-butyl-N-methyl-1-phenylpyrrolo 1,2-A]pyrazine-3-carboxamide by Rapid Expansion of Supercritical Solution on the Dissolution Kinetics from Tablets

2025, №3

сс. 42-49

Цитировать

V.B. Markeev, A.M. Vorobei, S.V. Tishkov, E.V. Blynskaya, O.O. Parenago, V.L. Dorofeev

Key words: rapid expansion of supercritical fluid, micronization, solubility, active pharmaceutical ingredient, tablets

N-Butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3) is a compound exhibiting both anxiolytic and antidepressant activity. Like most substances being developed as active pharmaceutical ingredients (API), it is practically insoluble in water, which may negatively affect its bioavailability and complicate tablet formulation. According to the Noyes—Whitney equation, solubilization of poorly water-soluble APIs may be achieved by increasing their contact surface area with the aqueous medium or by creating a supersaturated state in solution. The API surface area can be increased by micronization using the rapid expansion of supercritical solution (RESS) method. The solubility of GML-3 in CO2 allows its micronization via RESS and the development of tablets with micronized API. The aim of this study was to develop GML-3 tablets containing API micronized by RESS, with improved dissolution kinetics.