羧甲基壳聚糖/聚乙烯醇水凝胶处方及制备工艺优化

Optimization of formulation and preparation procedure of carboxymethyl chitosan/PVA hydrogels

目的:优选羧甲基壳聚糖(CMCS)/聚乙烯醇(PVA)水凝胶的处方及制备工艺;初步考察载药水凝胶的体外释药规律。方法:合成不同取代度的CMCS;以羧甲基壳聚糖的取代度,2%戊二醛的用量及温度为考察因素,各取三水平,以水凝胶在pH1.2溶液中的膨胀率为考察指标进行L9(34)正交实验;并以甲硝唑为模型药物,对水凝胶的体外释药做初步考察。结果:取代度为0.38的CMCS,在0.2mL的2%戊二醛做交联剂于室温下交联,有最大膨胀率(24.54±1.04)(n=3);以最佳条件制备的甲硝唑水凝胶于0.1mol.L-1盐酸溶液中在8h内累积释药率达(89.95±1.05)%(n=3)。结论:CMCS/PVA水凝胶最佳处方在pH1.2时具有理想的膨胀率,可做为胃部释药载体进一步研究。

OBJECTIVE To optimize formulation and preparation procedure of CMCS/PVA hydrogels and to study the model drug release from CMCS/PVA hydrogels in vitro. METHODS CMCSs with different substitution were synthesized. The substitution of CMCS,the amount of 2%glutaraldehyde and temperature as factors with three levels each,and swelling ratio of the hydrogels in pH of 1.2 as index, the orthogonal test was employed to optimize the formulation of the hydrogels. The model drug was Metronidazole, and its release from CMCS/PVA hydrogels was studied in vitro. RESULTS The optimum formulation and preparation procedure was as follows：when the substitution of CMCS was 0. 38 and the amount of cross-linking agent was 0. 2 mL at room temperature, the hydrogels had the largest swelling ratio of （24. 54 ± 1.04） （n = 3）. Metronidazole contained CMCS/PVA hydrogels was prepared according to the optimal formulation, and the accumulative release ratio in 0. 1 mol·L^-1 HC1 solution is up to （89. 95 ±1.05） %（n = 3） in 8 hours. CONCLUSION The optimum formulation and preparation procedure of CMCS/PVA hydrogels had a good swelling ratio in pH of 1.2. It is valuble to be further studied as a promising stomach-released carrier.