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

Abstract

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.

Development of a Carvedilol Oral Liquid Formulation for Paediatric Use

“…Approximately 70% of the new molecules developed as APIs are poorly soluble in water. Recent methods for increasing solubility include API and polymer composites obtained by creating amorphous solid dispersions [ 25 ], developing nanocarrier systems as nano-slow-release systems using mesoporous materials [ 26 ], and generating self-emulsifying systems (SEDDS), which are promising tools to enhance permeation across biological membranes [ 27 ].…”