Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
J Pharm Pharmacol. 2017 Oct;69(10):1284-1292. doi: 10.1111/jphp.12767. Epub 2017 Jun 20.
Mesoporous silicas (SLC) have demonstrated considerable potential to improve bioavailability of poorly soluble drugs by facilitating rapid dissolution and generating supersaturation. The addition of certain polymers can further enhance the dissolution of these formulations by preventing drug precipitation. This study uses fenofibrate as a model drug to investigate the performance of an SLC-based formulation, delivered with hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a precipitation inhibitor, in pigs. The ability of biorelevant dissolution testing to predict the in vivo performance was also assessed.
Fenofibrate-loaded mesoporous silica (FF-SLC), together with HPMCAS, displayed significant improvements in biorelevant dissolution tests relative to a reference formulation consisting of a physical mixture of crystalline fenofibrate with HPMCAS. In vivo assessment in fasted pigs demonstrated bioavailabilities of 86.69 ± 35.37% with combination of FF-SLC and HPMCAS in capsule form and 75.47 ± 14.58% as a suspension, compared to 19.92 ± 9.89% with the reference formulation. A positive correlation was identified between bioavailability and dissolution efficiency.
The substantial improvements in bioavailability of fenofibrate from the SLC-based formulations confirm the ability of this formulation strategy to overcome the dissolution and solubility limitations, further raising the prospects of a future commercially available SLC-based formulation.
介孔硅（SLC）已被证明具有通过促进快速溶解和产生过饱和来提高难溶性药物生物利用度的巨大潜力。添加某些聚合物可以通过防止药物沉淀进一步增强这些制剂的溶解性能。本研究以非诺贝特为模型药物，考察了基于 SLC 的制剂与作为沉淀抑制剂的羟丙甲纤维素醋酸琥珀酸酯（HPMCAS）一起在猪体内的性能。还评估了生物相关溶解试验预测体内性能的能力。
载有非诺贝特的介孔硅（FF-SLC）与 HPMCAS 一起，在生物相关溶解试验中相对于由结晶非诺贝特与 HPMCAS 的物理混合物组成的参比制剂显示出显著的改善。在禁食猪体内评估中，胶囊形式的 FF-SLC 和 HPMCAS 组合的生物利用度为 86.69±35.37%，混悬液形式为 75.47±14.58%，而参比制剂为 19.92±9.89%。生物利用度与溶解效率之间存在正相关关系。
基于 SLC 的制剂中非诺贝特生物利用度的显著提高证实了这种制剂策略克服溶解和溶解度限制的能力，进一步提高了未来基于 SLC 的商业制剂的前景。
