Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh, India.
Drug Deliv. 2009 Oct;16(7):405-15. doi: 10.1080/10717540903126314.
The aim of the present study was to formulate and evaluate buccoadhesive gels of model drug, glibenclamide indented as an alternate route of drug delivery to have enhanced bioavailability. The buccoadhesive gels were prepared by solution polymerization technique containing Hydroxy Propyl Methyl Cellulose (HPMC, E15 LV) and Carbopol (CP, 934P). An apparatus, simulating the in-vivo conditions of the mouth was designed in order to assess in-vitro release kinetics of the prepared gels. The gels were also evaluated for buccoadhesive strength, hydration, and swelling index, and viscosity. In-vivo evaluation for pharmacodynamic and pharmacokinetic properties of the optimized gel was done in rabbits. The drug release of buccoadhesive gels through rabbit buccal mucosa increased significantly (p < 0.05) by the use of penetration enhancers. The release kinetics followed Higuchi model with release mechanism being Fickian diffusion. In-vivo results of the optimized gel (2% CP: 2% HPMC) revealed that the gel successfully prevented severe hypoglycemia, showed sustained action, and enhanced relative bioavailability with and without penetration enhancers as compared to the marketed formulation. The buccoadhesive gels could possibly be a means for alternative dosage form in avoiding first pass metabolism and ensuring enhanced bioavailability for glibenclamide.
本研究的目的是制备和评价模型药物格列本脲的颊黏附凝胶，作为一种替代给药途径，以提高生物利用度。颊黏附凝胶采用溶液聚合技术制备，包含羟丙基甲基纤维素（HPMC，E15LV）和卡波姆（CP，934P）。为了评估制备凝胶的体外释放动力学，设计了一种模拟口腔体内条件的设备。还对凝胶的颊黏附强度、水合作用、溶胀指数和黏度进行了评价。在兔子体内对优化凝胶的药效学和药代动力学特性进行了评价。通过使用渗透增强剂，颊黏附凝胶通过兔颊黏膜的药物释放显著增加（p < 0.05）。释放动力学符合 Higuchi 模型，释放机制为菲克扩散。优化凝胶（2%CP：2%HPMC）的体内结果表明，与市售制剂相比，凝胶成功预防了严重低血糖，表现出持续作用，并在有和没有渗透增强剂的情况下提高了相对生物利用度。颊黏附凝胶可能是一种替代剂型的手段，可以避免首过代谢，确保格列本脲的生物利用度提高。
