Background: Simvastatin (SMV), a hypocholesterolemic agent, suffers from very low bioavailability due to its poor aqueous solubility and extensive first-pass metabolism.
Methods: Two SMV carrier systems, namely, polymeric drug inclusion complex (IC) and mixed micelles (MM) nanoparticles, were developed and loaded into mucoadhesive buccal films to enhance SMV bioavailability. The two carrier systems were characterized and their permeation across human oral epithelial cells (OEC) was studied. The effect of IC to MM ratio (X₁) and the mucoadhesive polymer concentration (X₂) on the cumulative percent of drug released, elongation percent and the mucoadhesive strength, from the prepared mucoadhesive films, were optimized. Ex vivo permeation across bovine mucosal tissue was investigated. The permeation parameters for the in vitro and ex vivo release data were calculated.
Results: Complexation of SMV with hydroxypropyl beta-cyclodextrin (HP β-CD) was superior to all other polymers as revealed by the equilibrium saturation solubility, stability constant, complexation efficiency and thermodynamic potential. SMV-HP β-CD IC was utilized to develop a saturated polymeric drug solution. Both carrier systems showed enhanced permeation across OEC when compared to pure drug. X₁ and X₂ were significantly affecting the characteristics of the prepared films. The optimized mucoadhesive buccal film formulation loaded with SMV IC and drug MM nanoparticles demonstrated superior ex vivo permeation when compared to the corresponding pure drug buccal film, and the calculated permeation parameters confirmed this finding.
Conclusion: Mucoadhesive buccal films containing SMV IC and drug MM can be used to improve drug bioavailability; however, additional pharmacokinetic and pharmacodynamic studies are required.



中文翻译：

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增强辛伐他汀从载有双药物释放载体的粘膜粘附颊膜的离体渗透。

背景：辛伐他汀（SMV）是一种降胆固醇药物，由于其水溶性差和首过代谢广泛，其生物利​​用度非常低。
方法：开发了两种 SMV 载体系统，即聚合物药物包合物 (IC) 和混合胶束 (MM) 纳米颗粒，并将其负载到粘膜粘附颊膜中，以增强 SMV 的生物利用度。对两种载体系统进行了表征，并研究了它们在人口腔上皮细胞 (OEC) 中的渗透性。_{优化了 IC 与 MM 的比例 (X 1} ) 和粘膜粘附聚合物浓度 (X ₂ ) 对所制备的粘膜粘附膜的药物释放累积百分比、伸长百分比和粘膜粘附强度的影响。研究了跨牛粘膜组织的离体渗透。计算了体外和离体释放数据的渗透参数。
结果：平衡饱和溶解度、稳定性常数、络合效率和热力学势表明，SMV 与羟丙基 β-环糊精 (HP β-CD) 的络合优于所有其他聚合物。利用 SMV-HP β-CD IC 开发饱和聚合物药物溶液。与纯药物相比，两种载体系统均表现出增强的 OEC 渗透性。X ₁和X ₂对所制备的薄膜的特性有显着影响。与相应的纯药物颊膜相比，装载有 SMV IC 和药物 MM 纳米颗粒的优化粘膜粘附颊膜制剂表现出优异的离体渗透性，计算的渗透参数证实了这一发现。
结论：含有SMV IC和药物MM的粘膜粘附颊膜可提高药物的生物利用度；然而，还需要额外的药代动力学和药效学研究。