Unit of Modeling and Experimental Biopharmaceutics, Centre of Chemical Bioactive, Central University of Las Villas, 54830, Santa Clara, Villa Clara, Cuba.
Department of Pharmacy and Pharmaceutical Technology, University of Valencia, 46100, Burjassot, Valencia, Spain.
AAPS PharmSciTech. 2018 May;19(4):1693-1698. doi: 10.1208/s12249-018-0982-7. Epub 2018 Mar 12.
The aim of the present study is to contribute to the scientific characterization of sildenafil citrate according to the Biopharmaceutics Classification System, following the World Health Organization (WHO) guidelines for biowaivers. The solubility and intestinal permeability data of sildenafil citrate were collected from literature; however, the experimental solubility studies are inconclusive and its "high permeability" suggests an API in the borderline of BCS Class I and Class II. The pH-solubility profile was determined using the saturation shake-flask method over the pH range of 1.2-6.8 at a temperature of 37 °C in aqueous media. The intestinal permeability was determined in rat by a closed-loop in situ perfusion method (the Doluisio technique). The solubility of sildenafil citrate is pH-dependent and at pH 6.8 the dose/solubility ratio obtained does not meet the WHO criteria for "high solubility." The high permeability values obtained by in situ intestinal perfusion in rat reinforce the published permeability data for sildenafil citrate. The experimental results obtained and the data available in the literature suggest that sildenafil citrate is clearly a Class II of BCS, according to the current biopharmaceutics classification system and WHO guidance.
本研究旨在根据世界卫生组织（WHO）关于生物豁免的指南，为枸橼酸西地那非的生物药剂学分类系统科学特征描述做出贡献。从文献中收集了枸橼酸西地那非的溶解度和肠道通透性数据；然而，实验性溶解度研究结果并不明确，其“高渗透性”表明该 API 处于 BCS 分类 I 和 II 的边界。使用饱和摇瓶法在 37°C 的温度下在 1.2-6.8 的 pH 范围内确定 pH-溶解度曲线，在水性介质中进行。通过闭路原位灌注法（Doluisio 技术）在大鼠中测定肠道通透性。枸橼酸西地那非的溶解度取决于 pH 值，在 pH 值 6.8 时，获得的剂量/溶解度比不符合 WHO 关于“高溶解度”的标准。在大鼠原位肠灌注中获得的高通透性值证实了已发表的枸橼酸西地那非的通透性数据。根据当前的生物药剂学分类系统和 WHO 指南，本研究获得的实验结果和文献中的数据表明，枸橼酸西地那非显然属于 BCS 分类 II。
