Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability

This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This a...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-07, Vol.24 (15), p.12215
Main Authors: Markeev, Vladimir B, Blynskaya, Evgenia V, Tishkov, Sergey V, Alekseev, Konstantin V, Marakhova, Anna I, Vetcher, Alexandre A, Shishonin, Alexander Y
Format: Article
Language:English
Subjects:
Alcohol
amorphous solid dispersions
Animal experimentation
Antidepressants
anxiolytics
bioavailability
composite
Crystal structure
Crystallization
Ethanol
Polyethylene glycol
Polymer industry
Polymers
R&D
Research & development
solubility
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Summary:This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water. The resulting differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and dissolution test data indicate that the resulting composites are amorphous at 1:15 API: polymer ratios for PVP and 1:5 for Soluplus , which ensures the solubility of GML-3 in purified water and maintaining the supercritical state in solution.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241512215