W. J. Irwin, M. Iqbal
Sep 20, 1991
Citations
0
Influential Citations
22
Citations
Journal
International Journal of Pharmaceutics
Abstract
Abstract α-Lactose monohydrate and bropirimine acetic acid solvate were used as model excipients and 4-methoxyphenyl aminoacetate hydrochloride was used as a model labile component to study the relationship between mechanical stress on solvates and the solid-state stability of a drug component. The effect of grinding the solvates was to disrupt the integrity of the associated solvent. When samples were examined by differential scanning calorimetry this change was characterised by a broadening of the endotherm due to desolvation and a lowering of the peak maximum temperature ( t max ) of the endothermic transition. This represents a weakening of the intermolecular forces which hold the solvent within the crystal. When 4-methoxyphenyl aminoacetate hydrochloride, a substrate which undergoes ready hydrolysis, is mixed with the solvates solid-state degradation rates, yielding 4-methoxyphenol are enhanced. The greatest effect is observed in samples where the solvate has been ground, suggesting that the enhanced lability of the solvent promotes solid-state degradation to a significant degree.