Xu Yuanlong, Mao Lijuan, Li Xueming, Wang Yonglu, Wei Ping
College of Pharmacy, Nanjing University of Technology, Jiangsu, PR China.
Pak J Pharm Sci. 2013 May;26(3):495-502.
As a representative proton pump inhibitor, Lansoprazole was poorly soluble in water which caused the low oral bioavailability. The present study was carried out to enhance the dissolution of lansoprazole by cogrinding with some commonly used hydrophilic polymers (β-CD, PVP, HPMC, L-HPC, CS, PEG and PVPP) in the weight ratio of 1:1 for 2 h in the jar mill. Samples of coground mixture, micronised drug, and physical mixture were characterized by XRPD, and DSC, the results showed that the drug crystallinity reduced in the coground process. The amount of drug released from the coground mixtures in PBS (pH 6.8, 37°C) in 30 min was 100% approximately (except the coground mixtures prepared with VPP or PEG) while released from the micronised drug was just about 20%. Increasing the hydrophilicity and diminishing the size of drug particles by cogrinding were the main causes for enhancing the dissolution of the drug. The results of the stability study of lansoprazole in coground mixture showed that there were no significant changes in the drug content and dissolution characteristics 6 months later. It is clear that the cogrinding method described in the article is very effective for enhancing the dissolution of the poorly soluble drugs, and it is easy for industrialization, showing a strong potential for future applications.
作为一种代表性的质子泵抑制剂，兰索拉唑在水中溶解度较差，导致口服生物利用度较低。本研究通过在罐磨机中以1:1的重量比与一些常用的亲水性聚合物（β-环糊精、聚乙烯吡咯烷酮、羟丙基甲基纤维素、低取代羟丙基纤维素、壳聚糖、聚乙二醇和交联聚乙烯吡咯烷酮）共研磨2小时来提高兰索拉唑的溶出度。通过X射线粉末衍射（XRPD）和差示扫描量热法（DSC）对共研磨混合物、微粉化药物和物理混合物的样品进行了表征，结果表明在共研磨过程中药物结晶度降低。在30分钟内，共研磨混合物在pH值为6.8、37°C的磷酸盐缓冲盐溶液（PBS）中的药物释放量约为100%（用交联聚乙烯吡咯烷酮或聚乙二醇制备的共研磨混合物除外），而微粉化药物的释放量仅约为20%。通过共研磨增加药物亲水性并减小药物颗粒尺寸是提高药物溶出度的主要原因。兰索拉唑在共研磨混合物中的稳定性研究结果表明，6个月后药物含量和溶出特性没有显著变化。显然，本文所述的共研磨方法对于提高难溶性药物的溶出度非常有效，且易于工业化，具有很强的未来应用潜力。
