盐酸乐卡地平Ⅰ、Ⅱ晶型及无定型对制剂制备的影响
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篇名: 盐酸乐卡地平Ⅰ、Ⅱ晶型及无定型对制剂制备的影响
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摘要: 目的:研究盐酸乐卡地平Ⅰ、Ⅱ晶型及无定型对制剂制备的影响,为其制剂开发及一致性评价提供理论基础。方法:采用X-射线粉末衍射(XRD)、红外分光光度(IR)和差式扫描量热(DSC)法鉴定盐酸乐卡地平的3种晶型;采用XRD法比较粉粹、研磨、加压工艺,湿法制粒中黏合剂溶剂(水、乙醇)和干燥温度(50、60、70 ℃)对盐酸乐卡地平3种晶型稳定性的影响;比较3种晶型盐酸乐卡地平片在水、盐酸、pH 4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液4种介质中的体外溶出度。结果:XRD显示,Ⅰ、Ⅱ晶型均有特征衍射峰,且2 θ值不一致,无定型无特征衍射峰;IR显示,3种晶型具有不同的吸收强度和吸收峰数目;DSC显示,Ⅰ、Ⅱ晶型分别在194.6、207.3 ℃有明显吸热峰,无定型在86.1 ℃有明显吸热峰、 299.8 ℃有放热峰。粉粹、研磨、加压及干燥温度对3种晶型转变均无影响;湿法制粒时水对晶型转变无影响,乙醇会引起Ⅰ晶型的晶型转变。除在盐酸中Ⅰ晶型与Ⅱ晶型片比较f2=68外,4种介质中3种晶型盐酸乐卡地平片溶出度两两比较的f2均小于50。结论:XRD、IR、DSC法均能鉴定盐酸乐卡地平的3种晶型。用Ⅰ晶型制备盐酸乐卡地平片时,湿法制粒应避免使用乙醇作为黏合剂溶剂,建议使用水。不同晶型会影响所制盐酸乐卡地平片的体外溶出度。
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 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.
期刊: 2017年第28卷第10期
作者: 卜鑫珏,张涛,王驰,夏喜坚,陈国松
AUTHORS: BU Xinjue,ZHANG Tao,WANG Chi,XIA Xijian,CHEN Guosong
关键字: 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 hydrochloride; Ⅰcrystal form; Ⅱ crystal form; Amorphous; Identification; Stability; Dissolution in vitro
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