HYDRATION OF DRUG MOLECULES - CAVITY-INCLUSION OF WATER IN CRYSTALS OF LOPERAMIDE HYDROCHLORIDE TETRAHYDRATE

Single crystal X-ray determination of the hydration sites in loperamid e hydrochloride tetrahydrate reveals that both ordered and disordered water molecules are entrapped in cavities formed by the packing of dru g molecules around threefold crystallographic axes. The compound was o btained by recrystallization of loperamide HCl from ethanol and crysta llizes in the trigonal system, space group R3, with a = 22.497(3), c = 16.719(6)Angstrom, Z = 9 and D-c = 1.194g cm(-3); final R = 0.070 for 2029 observed data collected at 294K. The cation adopts an extended c onformation in the crystal and there is extensive hydrogen bonding inv olving water molecules, chloride ions and the cation O-H and N+-H grou ps, The compound was also characterized by hot-stage microscopy, therm ogravimetry, differential scanning calorimetry and X-ray powder diffra ction (XRD).