盐酸文拉法辛亲水/蜡质骨架缓释片的制备及其释药特性研究

Preparation and Release Characteristics of Venlafaxine Hydrochloride Hydrophilic and Lipidic Matrix Sustained-release Tablets

目的:制备盐酸文拉法辛亲水/蜡质骨架缓释片,考察其释药特性。方法:以山嵛酸甘油酯作为蜡质骨架、羟丙甲纤维素(HPMC)作为亲水凝胶骨架,通过单因素试验筛选辅料种类及用量;以4、8、24 h的累积释放量与理想值偏差之和作为评价指标,采用正交试验优化HPMC黏度、HPMC K15M用量和山嵛酸甘油酯用量,并通过不同方程拟合释放曲线。结果:最优处方为盐酸文拉法辛8.5 kg,HPMC K15M 15 kg,山嵛酸甘油酯26 kg,硬脂酸镁0.5 kg;所制骨架缓释片4、8、24 h的累积释放度分别为34.3%、63.9%、99.2%;体外释药符合一级释药特征,以骨架溶蚀机制为主。结论:成功制得缓释效果良好的盐酸文拉法辛亲水/蜡质骨架缓释片。

OBJECTIVE：To prepare Venlafaxine hydrochloride sustained-release tablets,and to investigate the characteristics of drug release. METHODS：Using glyceryl behenate as lipidic matrix material and HPMC as hydrophilic matrix material,the kind and dosage of excipients were screened by single factor experiment. Using 4,8,24 h accumulative release rate and the deviation summation of ideal values as index,the viscosity of HPMC,the amounts of HPMC K15 M and glyceryl behenate were optimized by orthogonal test. The dissolution curves were fitted by different equations. RESULTS：The optimal formulation was as follows as venlafaxine hydrochloride 8.5 kg,HPMC K15 M 15 kg,glyceryl behenate 26 kg,magnesium stearate 0.5 kg. 4,8,24 h accumulative release rates of prepared matrix sustained-release tablets were 34.3%,63.9% and 99.2%,respectively. The releases profiles of hydrophilic and lipidic matrix sustained release tablets followed first-order equation in vitro mainly through matrix erosion. CONCLUSIONS：Venlafaxine hydrochloride hydrophilic and lipidic matrix sustained-release tablets with good sustained-release effect have been prepared successfully.