阿莫西林黏膜黏附微球稳定性及黏附性研究

 目的比较pH 1盐酸溶液条件下阿莫西林原料药与黏膜黏附微球中阿莫西林稳定性,考察阿莫西林黏膜黏附微球(Amo-Cb-Ec)与阿莫西林乙基纤维素微球(Amo-Ec)体内外黏膜黏附效果。方法用乳化-溶媒蒸发法制备Amo-Cb-Ec和Amo-Ec;以高效液相色谱法测定Amo-Cb-Ec中阿莫西林及阿莫西林原料药在pH 1条件下稳定性;分别以拉力法和冲洗法考察Amo-Cb-Ec与离体大鼠肠黏膜和胃黏膜表面的黏附效果;以灌胃法考察微球在大鼠胃肠道黏附滞留程度。结果pH 1条件下,37℃振荡放置6 h,阿莫西林原料药降解大于50％,含0.5％卡波普有助于减少其降解程度,而Amo-Cb-Ec中阿莫西林相对含量均在85％左右。Amo-Cb-Ec与大鼠离体肠黏膜间黏附力显著高于不含黏附材料的Amo-Ec(P<0.05);Amo-Cb-Ec在大鼠离体胃黏膜表面滞留率显著高于Amo-Ec(P<0.05);Amo-Cb-Ec在大鼠胃肠道内的滞留率也显著高于Amo-Ec。结论在pH 1条件下游离阿莫西林不稳定,而卡波普对阿莫西林具有一定保护作用,Amo-Cb-Ec中所含阿莫西林稳定程度显著提高。体内外黏附试验结果显示,Amo-Cb-Ec对离体和活体胃黏膜具有良好的黏附作用。

Study on mucoadhesiveness and stability of mucoadhesive microspheres loading amoxicillin

OBJECTIVE To study the stabihty of amoxicillin and amoxicillin entrapped in mucodhesive microspheres in gastric acid. Both in vitro and in vivo mucoadhesiveness effects of the microspheres were investigated. METHODS The mucoadhesive microspheres entrapping amoxicillin (Amo-Cb-Ec microspheres) were prepared using emulsification/evaporation method.The stabihty of amoxicillin and amoxicillin entrapped in microspheres in HCl media (pH=1) was determined and compared by HPLC method.The adherence between Amo-Cb-Ec and intestinal mucous membranes was measured by detaching the microspheres away from the mucous membrane using torsion balance. The in vitro and in vivo adhesion tests were carried out respectively, by counting the microspheres retaining either on the surface of gastric mucous membrane of mice or in the gastrointestinal tracts of rats. RESULTS In diluted HC1 solution ( pH = 1) at 37℃ for 6 h, about 50% of amoxicillin was decomposed, while in the medium containing 0.5% carpobol at the same pH, the amoxicillin decomposition was reduced. Amoxicillin entrapped in mucoadhesive microspheres was much more stable. The adhesion of Amo-Cb-Ec microspheres was significantly stronger than that of the Amo-Ecmicrospheres(P<0.05) ;and the retention rate of Amo-Cb-Ec microspheres, on the surface of gastric mucosa,was markedly higher than those without bioadhesive polymers in their formulae (Amo-Ec microspheres) (P<0.05). In vivo test, the retention rate of Amo-Cb-Ec microspheres in the gastrointestinal tract of rats was also higher than that of Amo-Ec microspheres. CONCLUSION The medium pH had an important influence on amoxicillin stability. Amoxicillin was unstable in HC1 solution and its release rate from microspheres can't be measured directly in HCl solution. Carbopol showed a protecting effect to amoxicillin from being decomposed by HC1 solution. Both in vitro and in vivo adhesion tests showed that Amo-Cb-Ec microspheres had good gastrointestinal mucoadhesiveness.