title: Demonstration of a shear-based solid-state phase transformation in a small molecular organic system: chlorpropamide.
abstract: Elucidation of the mechanisms for mechanically activated phase transformations of API are necessary for progress in materials and process understanding. The mechanically induced solid-state transformation between the A and C enantiotropes of the anti-diabetic drug chlorpropamide (C(10)H(13)ClN(2)O(3)S) was investigated. The structure of the high temperature stable phase (form C) was solved using powder X-ray data. Transmission powder X-ray diffraction (PXRD) and Raman spectroscopy were used for in situ quantification and analysis of the phase interconversion that occurs as a function of applied pressure during compaction. Each polymorph was observed to undergo a solid-state transition, which increased with pressure to a maximum extent that corresponded with the consolidation limit of the respective bulk powder. Neither form was observed to convert under hydrostatic pressure, suggesting a shear dependence for interconversion at compaction pressures. Examination of the two crystallographic structures indicated that both forms have a common slip system and preserved molecular positions. It is suggested that the transformation of either form is allowed when resolved shear stresses initiate deformation, causing lattice distortion, which allows the simultaneous reconformation of molecules.
authors: Duquesne University Mylan School of Pharmacy, 600 Forbes Avenue, Pittsburgh, Pennsylvania 15282, USA. wildfongp@duq.edu
authors: Peter L D
authors: PL
authors: Wildfong
authors: Kenneth R
authors: KR
authors: Morris
authors: Carl A
authors: CA
authors: Anderson
authors: Steven M
authors: SM
authors: Short
mesh_terms: D002152:Calorimetry, Differential Scanning; D002747:Chlorpropamide / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D004355:Drug Stability; D007004:Hypoglycemic Agents / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D044367:Phase Transition; D033362:Powder Diffraction; D011208:Powders; D011312:Pressure; D033081:Shear Strength; D013059:Spectrum Analysis, Raman; D013314:Stress, Mechanical; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D007004:Hypoglycemic Agents; D011208:Powders; D002747:Chlorpropamide