Puttipipatkhachorn S, Nunthanid J, Yamamoto K, Peck G E
Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
J Control Release. 2001 Jul 10;75(1-2):143-53. doi: 10.1016/s0168-3659(01)00389-3.
Four different grades of chitosan varying in molecular weight and degree of deacetylation were used to prepare chitosan films. Salicylic acid and theophylline were incorporated into cast chitosan films as model acidic and basic drugs, respectively. Crystalline characteristics, thermal behavior, drug-polymer interaction and drug release behaviors of the films were studied. The results of Fourier transform infrared and solid-state 13C NMR spectroscopy demonstrated the drug-polymer interaction between salicylic acid and chitosan, resulting in salicylate formation, whereas no drug-polymer interaction was observed in theophylline-loaded chitosan films. Most chitosan films loaded with either salicylic acid or theophylline exhibited a fast release pattern, whereas the high viscosity chitosan films incorporated with salicylic acid showed sustained release patterns in distilled water. The sustained release action of salicylic acid from the high viscosity chitosan films was due to the drug-polymer interaction. The mechanism of release was Fickian diffusion control with subsequent zero order release. It was suggested that the swelling property, dissolution characteristics of the polymer films, pK(a) of drugs and especially drug-polymer interaction were important factors governing drug release patterns from chitosan films.
使用四种不同分子量和脱乙酰度的壳聚糖制备壳聚糖膜。分别将水杨酸和茶碱作为模型酸性和碱性药物掺入浇铸的壳聚糖膜中。研究了膜的结晶特性、热行为、药物-聚合物相互作用和药物释放行为。傅里叶变换红外光谱和固态13C核磁共振光谱结果表明水杨酸与壳聚糖之间存在药物-聚合物相互作用，导致水杨酸盐形成，而在载有茶碱的壳聚糖膜中未观察到药物-聚合物相互作用。大多数载有水杨酸或茶碱的壳聚糖膜呈现快速释放模式，而掺入水杨酸的高粘度壳聚糖膜在蒸馏水中呈现缓释模式。水杨酸从高粘度壳聚糖膜中的缓释作用归因于药物-聚合物相互作用。释放机制是菲克扩散控制随后为零级释放。有人提出，聚合物膜的溶胀性能、溶解特性、药物的pK(a)，尤其是药物-聚合物相互作用是决定壳聚糖膜药物释放模式的重要因素。
