盐酸厄洛替尼晶型研究

摘要

Objective: To identify the polymorph crystal A and B of erlotinib hydrochloride, to learn the influence of preparation process on crystal stability and to determine the development process of er-lotinib hydrochloride tablets with polymorph A. Methods: X-ray diffraction (XRD), infrared spectrophotome-try (IR), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were applied to study the polymorph A and B of erlotinib hydrochloride for their physicochemical properties and the crystal transformation between A and B. In addition, in vitro dissolution tests were conducted to determine the dissolution profiles of each crystal form and the development process was also studied preliminarily. Re-sults: Polymorph A and B demonstrated explicit disparity in crystal form characteristic, dissolution rate and stability, wherein polymorph A was thermodynamically unstable with better solubility and faster dissolution rate. Wetting agent added in wet granulation would transform crystal A into B. Conclusion: This study in-dicates that XRD, IR, SEM and DSC can be used to identify polymorphs rapidly and accurately. To devel-op erlotinib hydrochloride tablets of polymorph A by dry granulation process, the stability of polymorph should be ensured by improving packaging technology.%目的：对盐酸厄洛替尼A晶型、B晶型进行鉴定，了解制剂过程对晶型稳定性的影响，确定A晶型盐酸厄洛替尼片的开发工艺。方法：通过X射线粉末衍射（XRD）、红外分光光度法（IR）、电镜扫描（SEM）和差式扫描量热分析（DSC），对两种晶型进行鉴定。通过XRD技术对晶型的转化进行研究，并比较两种晶型的理化性质及片剂在溶出介质中的溶出行为差异，对片剂的工艺开发进行初步研究。结果：两种晶型具有不同的晶型特征。 A晶型溶解性好，溶出速度快，稳定性差；而B晶型具有较好的稳定性。湿法制粒中润湿剂的加入会导致A晶型转变为B晶型。结论：采用XRD、IR、SEM和DSC技术可以对药物晶型进行快速、准确的鉴定。以A晶型替代B晶型制备盐酸厄洛替尼片，采用干法制粒，但需改善包装，保证晶型的稳定性。