Effects ofⅠ,ⅡCrystal and Amorphous Forms of Lercanidipine Hydrochloride on the Preparation / 中国药房

ABSTRACT

OBJECTIVE:To study the effects of Ⅰ,Ⅱ crystal and amorphous forms of lercanidipine hydrochloride on the preparation,and provide theoretical basis for its development and consistency evaluation. METHODS:X-ray powder diffraction (XRD),infrared spectrophotometry(IR)and differential scanning calorimetry(DSC)were adopted to identify the 3 crystal forms of lercanidipine hydrochloride. XRD was used to compare the effects of crushing,grinding,pressing technology,wetting granula-tion,adhesive solvents(water,ethanol)and drying temperature(50,60,70℃)on stability of 3 crystal forms of lercanidipine hy-drochloride;the dissolution in vitro in water,hydrochloride,pH 4.5 acetate buffer,pH 6.8 phosphate buffer were compared among 3 crystal forms of Lercanidipine hydrochloride tablet. RESULTS:XRD showed both Ⅰ,Ⅱ crystal forms had characteristic diffrac-tion peak with inconsistent 2 θ values,amorphous had no characteristic diffraction peak;IR showed 3 crystal forms had different absorption intensity and absorption peak number;DSC showed Ⅰ,Ⅱ crystal forms had obvious endothermic peak in 194.6 ℃, 207.3 ℃,respectively,amorphous had obvious endothermic peak in 86.1 ℃ and exothermic peak in 299.8 ℃. Crushing,grinding, pressing and drying temperature had no effects on the stability of 3 crystal forms;water had no effect on the stability of crystal in wetting granulation,ethanol may cause the change of Ⅰcrystal form. Except for the comparison between Ⅰ,Ⅱ crystal forms in hydrochloride (f2=68),the dissolution f2 of 3 crystal forms in 4 kinds of medium were lower than 50. CONCLUSIONS:XRD, IR,DSC methods can identify the 3 crystal forms of Lercanidipine hydrochloride tablet. When preparing lercanidipine hydrochlo-ride by Ⅰcrystal form,wetting granulation should avoid using ethanol as a adhesive solvent,instead of water. Different crystal forms can affect the dissolution in vitro of prepared Lercanidipine hydrochloride tablet.