盐酸青藤碱延迟起释缓释片的研制

目的:研制盐酸青藤碱延迟起释型缓释片。方法:采用干法压制包衣法制得盐酸青藤碱延迟起释型缓释片,以片芯和衣膜中HPMC用量比例为影响因素,以释药时滞和释药速度常数为评价指标,采用星点设计试验,多元线性回归及二项式方程拟合建立指标与因素之间的数学关系,通过效应面法优化其处方,并对优化结果进行验证;对延迟缓释片时滞后6~15 h的释药数据进行零级、Higuchi和Peppas方程拟合,解析其释药机制。结果:释药时滞和释药速度常数与两因素之间均可用二项式方程拟合,相关系数分别为0.990 1和0.987 6,优化处方的释药时滞和释药速度常数实测值与预测值偏差分别为-3.15%和-0.34%,优化处方制得盐酸青藤碱延迟起释型缓释片释药时滞约6 h,药物在6~15 h内近似于零级释放,释药机制为骨架溶蚀释药。结论:盐酸青藤碱延迟片具有时滞后药物缓慢释放的释药特性,所建立的数学模型预测性良好。

Preparation of sinomenine hydrochloride delayed-onset sustained-release tablets

Objective: To prepare sinomenine hydrochloride delayed-onset sustained-release tablets. Method: The tablets containing sinomenine hydrochloride were prepared by dry-compression coating technique with the ratio of HPMC in core tablet and the ratio of HPMC in coating film as the influence factors and the lag-time and release rate as the evaluation parameters. Experiments were done on the central composite design, the data were simulated by using multi-linear equation and second-order polynomial equation. The possibly optimal formulation was predicted by response surface method. The dissolution date(lag-time and release rate)of the tablets prepared under the optimum condition were compared with the predicted. The drug released mechanism of the tablet were studied by Model-fitted of drug released within 6-15 h with zero-order, Higuchi and Peppas equation, respectively. Result: The lag-time and release rate were simulated using second-order polynomial equation,regression coefficients of the two parameters were 0.990 1 and 0.987 6,respectively. Bias between the observed and predicted values of lag-time and release rate were -3.15% and -0.34%,respectively. The lag-time of the tablet prepared under the optimum condition in vitro was about 6 h, then drug released from the tablet within 6-15 h was found to conform to zero-order kinetics and was controlled by bulk erosion mechanism. Conclusion: Sinomenine hydrochloride delayed-onset sustained-release tablets release drug slowly after lag time. The models developed in this study are proved to be highly predictable.