Journal
CRYSTENGCOMM
Volume 11, Issue 3, Pages 493-500Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/b812264d
Keywords
-
Categories
Funding
- Warner Lambert/Parke Davis fellowship
- College of Pharmacy
- University of Michigan, Ann Arbor, MI,
Ask authors/readers for more resources
The purpose of this study was to investigate whether cocrystals form by simply mixing pure solid components without the need to comill. The effects of moisture and temperature during storage were studied in binary mixtures where pure components were exposed to different levels of mechanical stress: (a) two components unmilled, (b) one component milled, or (3) two components individually milled. Equimolar mixtures of anhydrous monoclinic form III carbamazepine (CBZ) with form I nicotinamide (NCT) or saccharin (SAC) were stored at 25 degrees C-75% RH, 45 degrees C-0% RH and 45 degrees C-75%RH. Transformation to cocrystal was monitored by FTIR and XRPD. Results show that conversion to cocrystal occurs even when components are not mechanically stressed at all storage conditions within 3 months except for unmilled CBZ/SAC at 25 degrees C-75%RH. Free energy calculations from solubilities and equilibrium constants confirm that transformation from reactants to cocrystal is thermodynamically favorable. Increasing temperature and relative humidity as well as mechanical activation by individually milling reactants enhances cocrystal formation. CBZ-NCT cocrystal forms faster than CBZ-SAC at all storage conditions. A metastable CBZ-SAC polymorph was detected in mixtures of individually milled CBZ and SAC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available