Synchronization of Cocrystal Dissolution and Drug Precipitation to Sustain Drug Supersaturation

Mol Pharm. 2022 Aug 1;19(8):2765-2775. doi: 10.1021/acs.molpharmaceut.2c00122. Epub 2022 Jul 14.

Abstract

A graphical analysis of both drug and coformer concentrations contributed by dissolving cocrystals is presented in the context of a simplified cocrystal phase diagram. The conceptual basis and analysis identify parameters that control cocrystal dissolution-drug supersaturation-precipitation (DSP) behavior. The important effects of coformer concentration, cocrystal dose, and cocrystal solubility on drug supersaturation levels are demonstrated and quantified by the DSPindex. While the studies presented rely on high and nonstoichiometric coformer concentrations contributed by the dissolving cocrystals, the concepts and findings can answer the question of whether and how much coformer should be added to cocrystal dissolution media or formulations.

Keywords: cocrystal phase diagram; cocrystal solubility; coformer concentration; critical supersaturation; dose number; solution-mediated phase transformation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Crystallization
  • Drug Compounding
  • Solubility*