An investigation of the causes of cocrystal dissociation at high humidity.
The dissociation at high humidity of cocrystals formed between caffeine and theophylline with a series of dicarboxylic acids is investigated and found to be driven by the partial dissolution of the acid, rather than by the formation of caffeine/theophylline hydrate. It is shown that partial dissociation occurs under all humidity conditions, and that cocrystals of compounds which do not form hydrates also dissociate by this mechanism. The observations made in this study indicate that cocrystal instability at high humidity will be a widespread issue, especially for cocrystals where the two coformers have widely differing aqueous solubilities, as is likely for systems where cocrystallisation is being used as means of improving the aqueous solubility, or dissolution rate, of a compound.
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom. Electronic address: mde32@cam.ac.uk.
Mark D
MD
Eddleston
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
Ranjit
R
Thakuria
Pfizer, Discovery Park House, Sandwich, United Kingdom.
Barry J
BJ
Aldous
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
William
W
Jones
D002110:Caffeine / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D004355:Drug Stability; D006813:Humidity; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013806:Theophylline / Q000737:chemistry; D014867:Water / Q000737:chemistry
D004364:Pharmaceutical Preparations; D014867:Water; D002110:Caffeine; D013806:Theophylline
X-ray powder diffractometry; co-crystals; hydrates/solvates; physical stability; solid state; solubility