两种pH敏感的羟丙基甲基纤维素衍生物的合成及性质研究

用醋酸酐(AA)和四氢苯酐(THPA)或甲基四氢苯酐(MTHPA)对羟丙基甲基纤维素(HPMC)进行化学修饰,合成了醋酸羟丙基甲基纤维素四氢酞酸酯(HPMCATH)和醋酸羟丙基甲基纤维素甲基四氢酞酸酯(HPMCAMT),对其酸值、pH敏感值、膜透湿性等性质进行了初步探讨,并用双氯酚酸钠为模型药物进行包衣片剂的体外释放实验.结果表明,两类pH敏感的高分子材料成膜性良好,HPMCATH的pH敏感值为5.2～5.6,HPMCAMT的pH敏感值为6.3～7.2,以HPMCAMT-4作为膜材料制备的包衣片在0.1mol/L盐酸中2h未见药物释放,在pH6.8的缓冲液中3h药物释放很少,在pH7.2缓冲液快速释放.HPMCAMT有可能作为结肠处药物定位释放包衣材料.

Synthesis and Characterization of Two pH-Sensitive HPMC Derivatives

Hydroxypropylmethylcellose （HPMC） was chemically modified, using acetic anhydride （AA） and tetrahydrophthalic anhydride （THPA） or methyltetrahydrophthalic anhydride （MTHPA）, to obtain pH-sensitive polymers,hydroxypropylmethylcellulose acetate tetrahydrophtalate （HPMCATH）or hydroxypropylmethylcellose acetate methyhetrahydrophtalate （HPMCAMT）. The pharmaceutical properties of HPMCATH and HPMCAMT, such as acid values,pH-sensitive values,water vapor permeability were investigated. Dielofanac sodium was chosen as model drug to prepare coating tablet. In vitro release of diclofanac sodium tablets coated with HPMCAMT were studied. HPMCATH and HPMCAMT showed good filming property. The pH-sensitive values of HPMCAMT were 6.3 to 7.2 while those of HPMCATH were 5.2 to 5.6. In vitro results showed that HPMCAMT-4 could completely suppress drug release within 2 h in 0.1 mol/L hydrochloric acid. Tablets coated with HPMCAMT hardly release drug within 3 h in 6.8 buffer solution,while they rapidly release drug in 7.2 buffer solution. HPMCAMT may be a useful material for a novel oral colon-specific drug delivery system.