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Vladimir B. Markeev, Vladimir P. Vinogradov, Sergej V. Tishkov, Evgenija V. Blynskaya, Konstantin V. Alekseev, Vladimir L. Dorofeev
Influence
of amorphous solid dispersions with a grafted copolymer of
polyvinylcaprolactam, polyvinyl acetate, and polyethylene glycol on the crystallinity
and kinetics of dissolution of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide
Abstract
Abstract. The problem of
poor solubility in water, which usually negatively affects the bioavailability
of oral medications, is a characteristic of most molecules (up to 70%)
developed as active pharmaceutical ingredients (API). Amorphous solid
dispersions of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide
(GML-3) with Soluplus® polymer have been developed. The inclusion of
GML-3, which is practically insoluble in water and has an antidepressant and
anxiolytic effects in solid dispersions, made it possible to transfer it from a
crystalline to an amorphous state. The amorphousness of solid dispersions was
confirmed by powder X-ray diffractometry (PXRD) and differential scanning
calorimetry (DSC), and the interaction of polymer and GML-3 inside the dispersions
was revealed. As a result of studying the effect of amorphous solid dispersions
with Soluplus® on the dissolution kinetics of GML-3, it was possible
to achieve the solubility of GML-3 in water at the level of 98,4%, which solves
the problem of the solubility of the API.
Key words: solid
dispersions, crystallinity, GML-3, Soluplus®, solubility
Copyright (C) Chemistry Dept., Moscow State University, 2002
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