Donato Eliane Maria, Martins Laura Alegria, Fröehlich Pedro Eduardo, Bergold Ana Maria
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul., Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
J Pharm Biomed Anal. 2008 Jul 15;47(3):547-52. doi: 10.1016/j.jpba.2008.02.014. Epub 2008 Feb 26.
The objective of the present study was to develop and validate a dissolution test for lopinavir soft gel capsules (Kaletra), using a simulated absorption profile based on in vivo data. Different conditions such as surfactant concentration, apparatus and rotation speed were evaluated. In vivo release profiles were obtained from the literature. The fraction (and percentage) of dose absorbed (FA) was calculated by using Wagner-Nelson method. The best in vitro dissolution profile was obtained using Apparatus 2 (paddle) at 25 rpm, 1000 ml of medium with 2.3% of sodium lauryl sulfate and pH 6.0. Under these conditions a level-A in vitro-in vivo correlation (IVIVC) was obtained (r = 0.997). The in vitro dissolution samples were analyzed using a HPLC method and the validation was performed according to USP protocol. The method showed accuracy, precision, linearity and specificity within the acceptable range. Both the HPLC method and the in vitro dissolution method were validated and could be used to evaluate the release profile of lopinavir soft gel capsules.
本研究的目的是基于体内数据开发并验证洛匹那韦软胶囊（克力芝）的溶出度试验，采用模拟吸收曲线。评估了不同条件，如表面活性剂浓度、装置和转速。从文献中获取体内释放曲线。采用Wagner-Nelson法计算吸收剂量分数（FA）及其百分比。使用桨法装置2，转速25 rpm，含2.3%十二烷基硫酸钠且pH值为6.0的1000 ml介质，获得了最佳的体外溶出曲线。在这些条件下，获得了A级体外-体内相关性（IVIVC）（r = 0.997）。采用HPLC法分析体外溶出样品，并根据美国药典规程进行验证。该方法在可接受范围内显示出准确性、精密度、线性和特异性。HPLC法和体外溶出度方法均经过验证，可用于评估洛匹那韦软胶囊的释放曲线。
