芬太尼双层缓释贴膜的研制及性质评价

Studies on preparation and evaluation of fentanyl bilayer sustained-release films

目的制备芬太尼双层口腔贴膜,并对其进行性能评价。方法以保护层和生物黏附层制备芬太尼双层口腔贴膜,并以贴膜的体外黏附力、体内黏附时间、释药行为及离体颊膜渗透能力等为指标,对贴膜的处方进行筛选。结果海藻酸钠与羧甲基纤维素钠及聚乙烯醇以2:1:2的比例制成的膜剂为最佳处方,其体外黏附力为(203±21)g·cm-2,口腔黏附时间为120 min,体外释药行为符合Higuchi方程。芬太尼的平均渗透速率为10.527μg·cm-2·h-1,其渗透过程属于零级动力学过程。加入甘草甜素前后,药膜的黏附力稍有下降,体外溶出速度与颊膜渗透速度均增加。结论芬太尼双层口腔贴膜有望成为芬太尼的新型透颊膜给药制剂。

OBJECTIVE To study and evaluate the formulation of bilayer oral mucoadhesive films of fentanyl. METHODS The mucoadhesive films were produced by spreading drug on bioadhesive and protective films. Their mucoadhesion in vitro and adhesive time in vivo, drug release rate and penetration through excised oral mucosa were investigated in order to determine an optimum formulation. RESULTS Alginate sodium, CMC-Na and PVA in a ratio of 2：1：2 were an optimum formulation, and its bioadhesive force was （203 ±21）g·cm^-2, the adhesive time in vivo was 120 rain. Its release curve eonformed to Higuchi formulation. A high permeation rate of 10.527μg·cm^-2·h^-1 was ,showed in vitro. The permeation of the oral mucoadhesive films followed the Fick＇s first diffusion law. The addition of glycyrrhizin to the films increased the fentanyl release rate and penetration, though a little decrease of bioadhesive force was deserved. CONCLUSION The fentanyl bilayer oral mucoadhesive films may be a promising vehicle for the transbuccal delivery of fentanyl.