Chen Sheng-Jun, Zhu Jia-Bi
Pharmaceutical Research Institute, China Pharmaceutical University, Nanjing 210009, China.
Yao Xue Xue Bao. 2005 Jul;40(7):606-10.
To prepare the combined system of diltiazem hydrochloride delayed-onset sustained-release pellets in order to make time-specific drug delivery system. The drug can release from the system sustained after a predetermined lag time, and the release behavior can continue till 24 hour after administrating the formulation. According to the concept of chronotherapy, the combined system is useful to improve the pharmacotherapy of cardiovascular diseases.
The velocity-time curve of the drug release from the multiple-unit system containing pellets was consistent with the fluctuation curve following time of blood pressure and heart ratio. So the velocity-time curve was selected to describe the release behavior of the combined system. The velocity-time equation describing the release behavior of two kinds of pellets was deduced by non-linear least square model fit. And zero-order kinetics equation was adopted to fit the release behavior of different combinations which were composed of different proportion of two kinds of pellets. The velocity-time equation describing the release behavior of the combinations was deduced by non-linear least square model fit, too. The difference of combinations in velocity-time curves between theoretical value and test value was compared.
The results showed that the test values were closely approximate to the theoretical values. Therefore, the multiple unit drug delivery system can be described by adding the velocity-time equations of different pellets to calculate the theoretical equations.
A multiple-unit combined system containing different coated pellets, as a novel delayed-onset sustained-release system, was prepared. Then a time-specific drug delivery system has been made. The programmed drug delivery system could be predicted by adding the velocity-time equation of each kind of pellets to calculate the theoretical equations. characterized by mathematics equation. The release behavior of pellets system could be characterized by mathematics equation.
制备盐酸地尔硫䓬延迟起效缓释微丸复合系统，以构建定时释药系统。该药物可在预定的滞后时间后从系统中持续释放，且释放行为可持续至给药后24小时。根据时辰治疗学的概念，该复合系统有助于改善心血管疾病的药物治疗。
含微丸的多单元系统中药物释放的速度-时间曲线与血压和心率随时间的波动曲线一致。因此，选择速度-时间曲线来描述复合系统的释放行为。通过非线性最小二乘模型拟合推导描述两种微丸释放行为的速度-时间方程。采用零级动力学方程拟合由两种微丸不同比例组成的不同组合的释放行为。同样通过非线性最小二乘模型拟合推导描述组合释放行为的速度-时间方程。比较组合在速度-时间曲线上理论值与试验值的差异。
结果表明试验值与理论值非常接近。因此，多单元给药系统可通过添加不同微丸的速度-时间方程来计算理论方程进行描述。
制备了一种包含不同包衣微丸的多单元复合系统，作为一种新型的延迟起效缓释系统。从而构建了定时释药系统。通过添加每种微丸的速度-时间方程来计算理论方程，可以预测程序控释给药系统。该系统以数学方程为特征。微丸系统的释放行为可用数学方程表征。
