无时滞非达霉素肠溶片的制备及溶出评价

Preparation and dissolution evaluation of fidaxomicin enteric coated tablets without time-lag effect

目的:制备无时滞非达霉素肠溶片,考察其溶出特性。方法:采用湿法制粒工艺,通过正交实验进行片芯优化,以甲基丙烯酸与丙烯酸乙酯共聚物为肠溶包衣材料,制备非达霉素肠溶片,以体外释放度为指标,考察其溶出行为。结果:片芯中羟丙甲纤维素和交联羧甲基纤维素钠的用量分别为1.2%和4.5%,微晶纤维素和淀粉的比例为3∶1,肠溶层共聚物的比例为50%时,制备的非达霉素肠溶片在pH1.0盐酸中2 h释放度小于10%,在pH4.5醋酸盐缓冲液中可以崩解释放,在pH6.8磷酸盐缓冲液中快速释放,10 min释放度大于60%。结论:制备的非达霉素肠溶片与普通肠溶片相比无时滞效应,有望进行工业化生产。

OBJECTIVE To prepare fidaxomicin enteric coated tablets without delayed release and study its dissolution peculiarity.METHODS Fidaxomicin enteric coated tablets were prepared by wet granulation and coated with copolymers derived from methacrylic acid/ethyl acrylate.Tablet core was optimized by orthogonal experiment design.In vitro dissolution method was used to observe drug release behaviors.RESULTS Content of hydroxy-propyl methyl cellulose in tablet core was 1.2% and croscarmellose sodium was 4.5%,ratio of microcrystalline cellulose/starch was 3∶1,content of coploymers in coating formulation was 50%.Release of enteric coated tablet was less than 10% in pH1.0hydrochloride acid in 2 h,while was more than 60% in pH6.8 phosphate buffer solution in 10 min,and tablets could release in pH4.5 acetate buffer solution.CONCLUSION Compared with common enteric coated tablets,fidaxomicin enteric coated tablets can release without delay effect,it is hopeful to be used in industrial production.