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 granulation, adhesive solvents (water, ethanol) and drying temperature (50, 60, 70 ℃) on stability of 3 crystal forms of lercanidipine hydrochloride; 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 diffraction 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 hydrochloride 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.
关键词
盐酸乐卡地平Ⅰ晶型Ⅱ晶型无定型鉴定稳定性体外溶出
Keywords
Lercanidipine hydrochlorideⅠcrystal formⅡ crystal formAmorphousIdentificationStabilityDissolution in vitro