Enhanced Boosting of Oral Absorption of Lopinavir Through Electrospray Coencapsulation with Ritonavir
Enhanced Boosting of Oral Absorption of Lopinavir Through Electrospray Coencapsulation with Ritonavir
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DOI：
10.1002/jps.24492
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发表时间：
2015-09-01
影响因子：
3.8
通讯作者：
Kawakami, Kohsaku
中科院分区：
文献类型：
--
作者：
Sakuma, Shinji;Matsumoto, Satoshi;Kawakami, Kohsaku
研究了吸收促进剂与低吸收性药物共包被在同一肠溶颗粒中的体内活性。洛匹那韦[细胞色素P450 3A （CYP3A）的底物]和利托那韦（CYP3A介导的代谢抑制剂）分别作为模型药物和模型吸收促进剂。采用同轴电喷雾沉积法将洛匹那韦和利托那韦包被成无定形肠包被颗粒。电喷雾处理显著改善了两种化合物的溶解分布，这可能是由于颗粒的完全非晶化和优异的分散效率。口服单独含洛匹那韦的肠溶颗粒后，观察到大鼠对洛匹那韦的吸收不良。当颗粒与单独含有利托那韦的肠溶颗粒共同施用时，洛匹那韦的吸收增强。当利托那韦与洛匹那韦共包被为相同的肠溶颗粒时，促进作用进一步增强。血浆浓度-时间曲线下面积的显著增加反映了平均停留时间的延长，而不是C-max的升高。洛匹那韦的吸收得到改善，可能是因为洛匹那韦总是伴随着实际量的利托那韦，以促进颗粒在胃肠道运输过程中。电喷雾共包技术不仅改善了药物的吸收，而且增加了谷浓度，从而减少了给药次数。(3)中国医药科学，2015,(4):391 - 391
In vivo activities of absorption enhancers coencapsulated with poorly absorptive drugs in the same enteric-coated particles were evaluated. Lopinavir [a substrate of cytochrome P450 3A (CYP3A)] and ritonavir (an inhibitor of CYP3A-mediatd metabolism) were used as a model drug and a model absorption enhancer, respectively. Lopinavir and ritonavir were encapsulated into enteric-coated particles as amorphous forms using coaxial electrospray deposition. The electrospray treatment resulted in dramatic improvement of dissolution profiles of both compounds, probably because of complete amorphization and superior dispersion efficiency of the particles. Poor absorption of lopinavir in rats was observed after oral administration of enteric-coated particles containing lopinavir alone. When the particles were coadministered with enteric-coated particles containing ritonavir alone, lopinavir absorption was boosted. The boosting effect was further enhanced when ritonavir was coencapsulated with lopinavir into the same enteric-coated particles. A significant increase in area under the plasma concentration-time curve reflected an extension of mean residence time rather than an elevation of C-max. Lopinavir absorption was improved presumably because lopinavir was always accompanied by a practical amount of ritonavir required for the boosting during the gastrointestinal transit of the particles. Not only did the electrospray coencapsulation technique improve drug absorption, but also increased trough concentration that might result in the reduction of the number of doses. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2977-2985, 2015