Hygroscopicity and Solubility of Noncrystalline Cephalexin

Abstract

Noncrystalline cephalexin (NC) was prepared by freeze-drying of a saturated solution of the drug. The results of X-ray diffractometry and polarizing microscopy indicated that NC was in a noncrystalline state. The nuclear magnetic resonance spectrum and the thin-layer chromatography behavior of NC were identical with those of crystalline cephalexin (CC). NC was stored under 0—95% relative humidity RH) at 35°C for 2 weeks. It absorbed about 1 mol of water at 20—32% RH, and about 2 mol of water at 43—66% RH, but there was no change in the X-ray pattern. When NC was stored at 75—95% RH, however, it absorbed more than 2 mol of water, and X-ray diffraction peaks appeared. This result suggests that NC was transformed into a partly crystalline state under conditions of 75—95% RH. The decomposition point (Dp) was measured with a differential thermal analysis (DTA) instrument. The Dp values of NC and CC were I73°C and 190°C, respective-ly. The Dp of the partly crystalline solid formed from NC under conditions of 75—95% RH was about 183°C. The solubility of NC in distilled water was examined by the equilibrium method. The amount of NC dissolved in distilled water at low temperatures reached a plateau, then decreased. This finding is due to the crystallization of NC. NC was about 6 times more soluble than CC solid at 10°C. The heat of solution for NC was calculated to be —3.24 kcal/mol from van’t Hoff plots of log Cs versus 1/T. © 1983, The Pharmaceutical Society of Japan. All rights reserved.