Biopharmaceutical characterization of sotalol-containing oral immediate release drug products
Biopharmaceutical characterization of sotalol-containing oral immediate release drug products
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DOI：
10.1016/j.ejpb.2004.02.007
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发表时间：
2004-07-01
影响因子：
4.9
通讯作者：
Oeser, H
中科院分区：
文献类型：
--
作者：
Alt, A;Potthast, H;Oeser, H
本研究的目的是通过生成适当的体外数据来取代体内生物等效性研究，以获得通用上市许可。测定盐酸索他洛尔的溶解度和渗透性，从而根据生物制药分类系统对该化合物进行分类。此外，不同Sota-saar（R）制剂和参比产品的体外溶出特性的比较研究为免除体内生物利用度（BA）/生物等效性（BE）研究提供了令人满意的理由。考虑到在pH值为1.0 - 7.5的水性介质（250 ml）中的最高剂量规格，进行了溶解度研究。使用人结肠直肠癌细胞系Caco-2研究渗透性。体外和体内数据表明药物化合物通过肠膜的渗透性高。因此，通过对溶解度和渗透性的评价，将盐酸索他洛尔归类为生物药剂学分类系统I类药物。体外溶出曲线表明，供试品和参比品的溶出速度相当（15 min内溶出率超过85%）。总之，满足相关先决条件可豁免BA/BE研究。(C)2004 Elsevier B. V.保留所有权利。
The objective of this study was replacing an in vivo bioequivalence study by generating suitable in vitro data in order to get generic marketing authorisation. Solubility and permeability of sotalol hydrochloride were determined thereby achieving classification of this compound according to the biopharmaceutical classification system. In addition comparative investigation of in vitro dissolution properties of different Sota-saar(R) formulations and the reference product provided satisfying justification to waive in vivo bioavailability (BA)/bioequivalence (BE) studies. The investigations on solubility were performed considering the highest dose strength in aqueous media (250 ml) with pH conditions between pH 1.0 and 7.5. Permeability was studied using the human colorectal carcinoma cell line Caco-2. In vitro as well as in vivo data suggest high permeability of the drug compound through the intestinal membrane. Thus, evaluation of solubility and permeability allow sotalol hydrochloride to be classified as biopharmaceutics classification system class I drug. In vitro dissolution profiles demonstrate comparable rapid dissolution (more than 85% in 15 min) for test and reference products. Summarizing, relevant prerequisites are fulfilled to waive BA/BE studies. (C) 2004 Elsevier B.V. All rights reserved.