对乙酰氨基酚鼻用温敏凝胶的制备及其体外释药机制研究

Preparation and Drug Release Mechanism in Vitro of Acetaminophen Nasal Thermosensitive Gel

目的:制备对乙酰氨基酚鼻用温敏凝胶,并对其体外释药机制进行研究。方法:以单用15%、16%、18%、20%、25%泊洛沙姆407(P407),及5%、10%P407与1%、1.5%、2%、2.5%、3%、4%聚乙烯醇(PVA)混合为凝胶基质制备对乙酰氨基酚鼻用温敏凝胶,根据胶凝温度筛选P407和PVA的最佳处方浓度,考察该凝胶的体外累积溶蚀量和体外释药行为并进行释放模型零级动力学、一级动力学、Higuchi方程、Riguchi-Peppas方程拟合。结果:单独使用P407作为凝胶基质,最佳处方浓度为16%～20%,凝胶的溶蚀和体外释药行为均符合零级动力学方程特征;选择混合基质,最佳处方浓度P407为10%,PVA为3%、4%,凝胶的溶蚀符合零级动力学方程特征,而体外释药遵从Higuchi方程,为骨架扩散释放机制。结论:PVA可显著降低P407的用量。单独使用P407作为凝胶基质,药物体外释药受凝胶溶蚀控制;而对于混合基质凝胶,溶蚀对体外释药并非决定性影响因素。

OBJECTIVE：To prepare Acetaminophen nasal thermosensitive gel,and to study drug release of it in vitro.METHODS：15%,16%,18%,20%,25% poloxamer 407（P407）alone,5% and 10% P407 mixed with 1%、1.5%、2%、2.5%、3%、 4% PVA were used as thermosensitive materials for gel.The best concentration of P407 and PVA in formulation was selected according to the gelating temperature.Drug release behavior and accumulative erosion amount of gel in vitro were investigated,and zero-order,first-order,Higuchi and Riguchi-Peppas equations were fitted.RESULTS：When use P407 alone as gel matrix,optimal concentration of P407 was from 16% to 20%;erosion and in vitro drug release of gel were in line with zero-order equation.When use P407 and PVA as gel matrix,the best formulation included optimal concentration of P407 was 10% and PVA was 3% or 4%;the erosion pattern of gel showed zero-order kinetic characteristics and drug release was in compliance with Higuchi equation,displaying framework diffusion release mechanism.CONCLUSION：The addition of PVA can reduce the amount of P407 significantly.When use P407 alone as matrix,drug release is controlled by gel erosion;for mixed matrix,erosion pattern is not decisive factor for drug release in vitro.