PDF(Pubmed)
Abstract：
The aim of this study was to design a novel matrix tablet with enhanced dissolution and pH-independent controlled release of sildenafil citrate (SIL), a drug with pH-dependent solubility, by using solid dispersions (SDs) and polyelectrostatic interactions. SIL-loaded SDs were prepared using various polymeric carriers such as poloxamer 188, poloxamer 407, Soluplus®, polyvinylpyrrolidone (PVP) K 12, and PVP K 17 by the solvent evaporation method. Among these polymers, Soluplus® was found to be the most effective in SDs for enhancing the drug dissolution over 6 h in pH 6.8 intestinal fluid. SIL was well dispersed in Soluplus®-based SDs in an amorphous form. When the Soluplus®-based SDs were added in the tablet containing positively charged chitosan and negatively charged Eudragit® L100, the drug release rate was further modulated in a controlled manner. The charge density of the tablet was higher at pH 6.8 than at pH 1.2 due to the polyelectrostatic interaction between chitosan and Eudragit® L100. This interaction could provide a pH-independent controlled release of SIL. Our study demonstrates that a combinatory approach of Soluplus®-based SDs and polyelectrostatic interactions can improve the dissolution and pH-independent release performance of SIL. This approach could be a promising pharmaceutical strategy to design a matrix tablet of poorly water-soluble drugs for the enhanced bioavailability.
摘要：
这项研究的目的是设计一种新型的基质片剂，具有增强的溶出度和不依赖pH的柠檬酸西地那非（SIL）的控释，具有pH依赖性溶解度的药物，通过使用固体分散体(SD)和聚静电相互作用。SIL负载的SD是使用各种聚合物载体制备的，例如泊洛沙姆188，泊洛沙姆407，Soluplus®，聚乙烯吡咯烷酮（PVP）K12和PVPK17通过溶剂蒸发法。在这些聚合物中，发现Soluplus®在SDs中最有效地增强药物在pH6.8肠液中的溶解超过6小时。SIL以无定形形式良好地分散在基于Soluplus®的SD中。当在含有带正电荷的壳聚糖和带负电荷的Eudragit®L100的片剂中添加基于Soluplus®的SD时,以受控方式进一步调节药物释放速率。由于壳聚糖和Eudragit®L100之间的多静电相互作用,片剂的电荷密度在pH6.8时比在pH1.2时高。这种相互作用可以提供SIL的非pH依赖性受控释放。我们的研究表明，基于Soluplus®的SD和多静电相互作用的组合方法可以改善SIL的溶解和不依赖pH的释放性能。这种方法可能是设计水溶性差的药物的基质片剂以提高生物利用度的有前途的药物策略。
