Yang Mingshi, Cui Fude, You Bengang, Wang Liang, Yue Peng, Kawashima Yoshiaki
Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Int J Pharm. 2004 Nov 22;286(1-2):99-109. doi: 10.1016/j.ijpharm.2004.08.007.
Nitrendipine, a dihydropyridine calcium antagonist, was used as a poorly water-soluble model drug. To improve its dissolution rate and extend the therapeutic period in vivo as well, a novel pH-dependent gradient-release drug delivery system for nitrendipine having a solid dispersed matrix structure was developed. Four factors, i.e. the amount of excipients, the pH of the dissolution medium, the rotating speed of the paddle of the dissolution apparatus and the particle size of the microspheres, all of which affect the drug-release behavior of the pH-dependent microspheres of the system were investigated in detail. The release profiles of the pH-dependent drug delivery system under simulated gastrointestinal tract pH conditions were also investigated. The results showed that the release rate of drug from the microspheres increased on increasing the amount of respective pH-dependent polymers formulated. Due to the fact that the active drug was incorporated in pH-dependent polymers and was present in a solid dispersion state in the microspheres, the release rate of the drug from the microspheres depended on the dissolution rate of the polymers, which was mainly influenced by the pH of dissolution medium, whereas the rotating speed of the paddle and the particle size of the microspheres had only a relatively minor effect. The release behavior of the system under simulated gastrointestinal tract conditions exhibited obvious gradient-release characteristics, showing that the release rate of the active drug could be controlled efficiently before the microspheres reached the appropriate region of the gut for absorption. These findings suggest that the pH-dependent drug delivery system could be fabricated by using present microspheres.
尼群地平是一种二氢吡啶类钙拮抗剂，用作水溶性差的模型药物。为了提高其溶解速率并延长体内治疗周期，开发了一种具有固体分散基质结构的新型尼群地平pH依赖型梯度释放药物递送系统。详细研究了四个因素，即辅料用量、溶出介质的pH值、溶出装置桨叶的转速和微球的粒径，所有这些因素都会影响该系统pH依赖型微球的药物释放行为。还研究了该pH依赖型药物递送系统在模拟胃肠道pH条件下的释放曲线。结果表明，随着所配制的各pH依赖型聚合物用量的增加，微球中药物的释放速率加快。由于活性药物被掺入pH依赖型聚合物中并以固体分散状态存在于微球中，药物从微球中的释放速率取决于聚合物的溶解速率，而聚合物的溶解速率主要受溶出介质pH值的影响，而桨叶转速和微球粒径的影响相对较小。该系统在模拟胃肠道条件下的释放行为呈现出明显的梯度释放特征，表明在微球到达肠道的适当吸收区域之前，活性药物的释放速率可以得到有效控制。这些研究结果表明，可以使用现有的微球来制备pH依赖型药物递送系统。
