两种pH敏感的羟丙甲纤维素衍生物的合成及性质比较

 目的制备两种pH敏感的羟丙甲纤维素(HPMC)衍生物,并研究其相关特性,以筛选适宜的十二指肠定位释药包衣材料。方法用偏苯三酸酐和顺丁烯二酸酐对HPMC进行化学修饰,对羟丙甲纤维素偏苯三酸酯(HPMCT)和醋酸羟丙基甲基纤维素顺丁烯二酸酯(HPMCAM)的性质如酸值、pH敏感值、膜透湿性、抗拉强度、玻璃化转变温度进行了初步探讨。并选用盐酸黄连素为模型药物进行包衣片剂的体外释放试验。结果两类pH敏感的高分子材料成膜性良好,并符合药剂学薄膜衣材料的有关要求。HPMCAM的pH敏感值为3.0～3.7,而HPMCT的pH敏感值为3.8～4.2。包衣片的体外释放试验表明,以HPM- CAM及HPMCT为膜材料制备的包衣片在人工胃液中2 h均未见药物释放,HPMCAM包衣片在pH 3.5左右可迅速释药,而HPMCT包衣片则在pH 4.2左右可迅速释药。结论HPMCAM可作为十二指肠溃疡时药物定位释放包衣材料,HPMCT可用于正常生理情况下十二指肠定位释药包衣材料。

Synthesis and characterization of two kinds of pH-sensitive HPMC derivatives

OBJECTIVE To synthesize and characterize pH-sensitive HPMC derivatives for use as a novel duodenum-specific coating agent. METHODS HPMC (hydroxypropyl methylcellulose) was chemically modified, using trimellic and maleic anhydrides, to obtain pH-sensitive HPMCT (hydroxypropyl methylcellulose trimellitate) and HPMCAM (hydroxypropyl methylcellulose acetate maleate) polymers. The pharmaceutical properties of HPMCAM and HPMCT, such as acid values, pH-sensitive values, water vapor permeability, tensile strength and Tg, were investigated. Berberine chloride was chosen as model drug to prepare coating tablets. In vitro release of berberine chloride tablets coated with HPMCAM and HPMCT were investigated. RESULTS The two kinds of materials showed good film forming property. The pH-sensitive values of HPMCT were 3.8 to 4.2, while those of HPMCAM were 3.0 to 3.7. In vitro results demonstrate that HPMCAM and HPMCT could completely suppress drug release within 2 h in simulated gastric fluid and the tablets coated with HPMCAM rapidly release the drug in phosphate buffer (pH 3.5) while those coated with HPMCT rapidly release drug in phosphate buffer (pH 4.2) .CONCLUSION These results indicate HPMCAM may be a useful material for a duodenum-specific drug delivery system and HPMCT may be used as an enteric coating agent.