Mechanisms by which moisture generates cocrystals

  • Jayasankar A
  • Good D
  • Rodríguez-Hornedo N
  • 111

    Readers

    Mendeley users who have this article in their library.
  • 80

    Citations

    Citations of this article.

Abstract

The purpose of this study is to determine the mechanisms by which moisture can generate cocrystals when solid particles of cocrystal reactants are exposed to deliquescent conditions (when moisture sorption forms an aqueous solution). It is based on the hypothesis that cocrystallization behavior during water uptake can be derived from solution chemistry using models that describe cocrystal solubility and reaction crystallization of molecular complexes. Cocrystal systems were selected with active pharmaceutical ingredients (APIs) that form hydrates and include carbamazepine, caffeine, and theophylline. Moisture uptake and crystallization behavior were studied by gravimetric vapor sorption, X-ray powder diffraction, and on-line Raman spectroscopy. Results indicate that moisture uptake generates cocrystals of carbamazepine-nicotinamide, carbamazepine-saccharin, and caffeine or theophylline with dicarboxylic acid ligands (oxalic acid, maleic acid, glutaric acid, and malonic acid) when solid mixtures with cocrystal reactants deliquesce. Microscopy studies revealed that the transformation mechanism to cocrystal involves (1) moisture uptake, (2) dissolution of reactants, and (3) cocrystal nucleation and growth. Studies of solid blends of reactants in a macro scale show that the rate and extent of cocrystal formation are a function of relative humidity, moisture uptake, deliquescent material, and dissolution rates of reactants. It is shown that the interplay between moisture uptake and dissolution determines the liquid phase composition, supersaturation, and cocrystal formation rates. Differences in the behavior of deliquescent additives (sucrose and fructose) are associated with moisture uptake and composition of the deliquesced solution. Our results show that deliquescence can transform API to cocrystal or reverse the reaction given the right conditions. Key indicators of cocrystal formation and stability are (1) moisture uptake, (2) cocrystal aqueous solubility, (3) solubility and dissolution of cocrystal reactants, and (4) transition concentration.

Author-supplied keywords

  • Cocrystal stability
  • Cocrystallization
  • Deliquescence
  • Hygroscopicity
  • Molecular complex
  • Phase transformation

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Adivaraha Jayasankar

  • David J. Good

  • Naír Rodríguez-Hornedo

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free