Hydration of drug molecules: cavityinclusion of water in crystals of loperamide hydrochloride tetrahydrate

Single crystal X-ray determination of the hydration sites in loperamide hydrochloride tetrahydrate reveals that both ordered and disordered water molecules are entrapped in cavities formed by the packing of drug molecules around threefold crystallographic axes. The compound was obtained by recrystallization of loperamide HCl from ethanol and crystallizes in the trigonal system, space group R3, with a = 22.497(3), c = 16.719(6)Å, 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 conformation in the crystal and there is extensive hydrogen bonding involving water molecules, chloride ions and the cation O-H and N + -H groups. The compound was also characterized by hot-stage microscopy, thermogravimetry, differential scanning calorimetry and X-ray powder diffraction (XRD).