Lapisteride

Ground CS-891 (N-[1-(4-methoxyphenyl)-1-methylethyl]-3-oxo-4-aza-5a-androst-1-ene-17β-carboxamide) of poorly water soluble drug was obtained using a Heiko Seisakusho model TI-100 vibration mill, and samples with different crystallinity were prepared at mixture ratios of 10:0, 7:3, 5:5, 3:7 and 0:10 (intact:ground CS-891).Physicochem. characterizations were obtained using qual. and quant. x-ray diffractometry, different scanning calorimetry (DSC), SEM, Quantasorb surface area analyzer, and controlled atm. microbalance.With increase of amorphous CS-891 in mixture ratios, the intensities of x-ray diffraction peaks of crystalline CS-891 were decreased, whereas surface area, water absorption, and exothermic peaks in DSC were increased.The apparent solubility of ground CS-891 was 4.4 μg/mL and the solubility of intact CS-891 was 3.1 μg/mL at 37 ± 1°.The apparent precipitation rates of CS-891 in a supersaturated solution during the solubility test were increased with an increase of amorphous CS-891, and a crystalline form of CS-891 transformed from amorphous CS-891 after the solubility test was found by x-ray diffraction anal., DSC and SEM.The dissolution profiles of CS-891 with different crystallinity at 37 ± 1° by the USP paddle method were investigated, and the apparent dissolution rate constant of ground CS-891 was about 5.9-fold higher than that of intact CS-891.A linear relationships between the crystallinity of CS-891 and the apparent dissolution rate constant (r > 0.96) were obtained.