Tapia Cristián, Escobar Zunilda, Costa Edda, Sapag-Hagar Jaime, Valenzuela Fernando, Basualto Carlos, Gai María Nella, Yazdani-Pedram Mehrdad
Laboratory of Unit Operations, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
Eur J Pharm Biopharm. 2004 Jan;57(1):65-75. doi: 10.1016/s0939-6411(03)00153-x.
The aim of this work was to evaluate the possibility of using mixtures and/or polyelectrolyte complexes from both chitosan-alginate and chitosan-carrageenan as prolonged drug release systems. Different dissolution profiles were obtained by changing the polymer matrix system (chitosan-alginate or chitosan-carrageenan) and the method used to include these polymers into the formulation (physical mixture or polyelectrolyte complex). Drug dissolution profiles from the matrices have been discussed by considering the swelling behavior of the polymers used. The swelling behavior of the chitosan-carrageenan and chitosan-alginate systems was analyzed by using the Hopfenberg model which permits to separate the diffusional contribution, kf, from the relaxational contribution, kr, involved in solvent penetration/sorption in glassy polymers. The chitosan-alginate system is better than the chitosan-carrageenan system as prolonged drug release matrix because the drug release is controlled at low percentage of the polymers in the formulation, the mean dissolution time is high, and different dissolution profiles could be obtained by changing the mode of inclusion of the polymers. Good agreement between td and kf/kr values for the system chitosan-alginate was found, which means that the swelling behavior of the polymers controlled the drug release from the matrix. In the case of the system chitosan-carrageenan, the high capacity of carrageenan promotes the entry of water into the tablet and therefore the main mechanism of drug release would be the disintegration instead of the swelling of the matrix.
本研究的目的是评估使用壳聚糖-海藻酸盐和壳聚糖-卡拉胶的混合物和/或聚电解质复合物作为长效药物释放系统的可能性。通过改变聚合物基质系统（壳聚糖-海藻酸盐或壳聚糖-卡拉胶）以及将这些聚合物纳入制剂的方法（物理混合物或聚电解质复合物），获得了不同的溶出曲线。通过考虑所用聚合物的溶胀行为，讨论了基质中的药物溶出曲线。利用霍普芬伯格模型分析了壳聚糖-卡拉胶和壳聚糖-海藻酸盐系统的溶胀行为，该模型允许将涉及玻璃态聚合物中溶剂渗透/吸附的扩散贡献kf与松弛贡献kr分开。壳聚糖-海藻酸盐系统作为长效药物释放基质优于壳聚糖-卡拉胶系统，因为在制剂中聚合物含量较低时药物释放就得到控制，平均溶出时间较长，并且通过改变聚合物的加入方式可以获得不同的溶出曲线。发现壳聚糖-海藻酸盐系统的td和kf/kr值之间具有良好的一致性，这意味着聚合物的溶胀行为控制了药物从基质中的释放。在壳聚糖-卡拉胶系统中，卡拉胶的高容量促进了水进入片剂，因此药物释放的主要机制将是崩解而不是基质的溶胀。
