4-氨基吡啶凝胶骨架缓释片的制备及体外释放

Preparation and drug release in vitro of 4-aminopyridine hydrophilic matrics sustained release tablets

目的:制备4-氨基吡啶(4-aminopyridine,4-AP)亲水凝胶骨架缓释片。方法:以羟丙甲纤维素的规格、处方用量及乳糖处方用量为因素设计正交试验,以体外释放度为考察指标,优化4-AP凝胶骨架片的处方,并进行批内和批间体外释放度验证试验。采用Origin软件对筛选出的最优处方释放度进行Weibull曲线拟合。考察体外释放条件对药物释放的影响。结果:优化处方为HPMC规格为K100LV,处方用量为54%,乳糖的处方用量为16%。所制得4-AP凝胶骨架片可持续释药12 h,批内释放均一性及批间重复性均良好。Weibull模型拟合方程得出药物释放符合一级速率过程。体外释放条件考察结果表明,转速对药物的释放有影响,而释放介质的种类和测定装置则无显著性影响。结论:所选4-AP凝胶骨架缓释片制备工艺可行,重复性好,有明显的缓释特性。

OBJECTIVE To prepare 4-aminopyridine（4-AP） hydrophilic matrics sustained release tablets.METHODS The formula of 4-aminopyridine（4-AP） hydrophilic matrics sustained release tablets was optimized by orthogonal experiment with the kind of HPMC and the amount of HPMC and lactose as factors and with the in vitro release rates as index.Meanwhile,the verification test on the intra-and inter-batch release rates of the samples was performed.Weibull model was used to make in vitro release fitting curve,and the influence of in vitro release conditions on the drug release was investigated.RESULTS The optimum formula could be seen as follows： the ratios of HPMC K100LV and lactose were 54% and 16% respectively.The formula achieved a sustained drug release of up to 12h,and both the intra-batch homogenicity and the inter-batch reproducibility were satisfactory.Weibull curve fitting equations showed that the drug release met level 1 rate process.The results of in vitro release test showed that drug release rate could be affected by the stirring rate,while the kind of media and device had no significant effect on it.CONCLUSION The preparation procedure of self-prepared 4-aminopyridine hydrophilic matrics sustained release tablets is feasible and repeatable.The tablets have obviously sustained property.