S K Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India.
J Microencapsul. 2009 Jun;26(4):365-76. doi: 10.1080/02652040802373012.
The purpose of this research was to formulate and systemically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use in the treatment of gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier polymer were prepared by an emulsion-solvent evaporation technique. Results of preliminary trials indicate that quantity of emulsifying agent, time for stirring, drug-to-polymers ratio and speed of rotation affected the characteristics of microspheres. Microspheres were discrete, spherical, free flowing and showed a good percentage of drug entrapment efficiency. An in vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to the gastric mucous layer and could retain in the gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (amoxicillin-ethyl cellulose-carbopol-934P) (X(1)) and stirring speed (X(2)) on dependent variables, i.e. percentage mucoadhesion, drug entrapment efficiency, particle size and t(80). The best batch exhibited a high drug entrapment efficiency of 56%; mucoadhesion percentage after 1 h was 80% and the particle size was 109 µm. A sustained drug release was obtained for more than 12 h. The drug-to-polymer-to-polymer ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied under a scanning electron microscope. In vitro release test showed that amoxicillin released slightly faster in pH 1.2 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin powder and mucoadhesive microspheres to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make a contribution to H. pylori complete eradication.
本研究的目的是制备并系统评估具有黏附性的阿莫西林微球的体外和体内性能，以期将其用于治疗与幽门螺杆菌相关的胃溃疡和十二指肠溃疡。阿莫西林黏附性微球以卡波姆-934P 作为黏附性聚合物，乙基纤维素作为载体聚合物，通过乳液-溶剂蒸发技术制备而成。初步试验结果表明，乳化剂的用量、搅拌时间、药物-聚合物比和转速均会影响微球的特性。制得的微球离散性好、呈球形、自由流动，且载药效率较高。体外黏附试验表明，阿莫西林黏附性微球与胃黏膜层的黏附性更强，并能在胃肠道中保持更长时间。采用 3(2)完全析因设计研究独立变量（阿莫西林-乙基纤维素-卡波姆-934P 比（X1）和搅拌速度（X2））对依赖变量（黏附百分比、载药效率、粒径和 t80）的影响。最佳批次的载药效率高达 56%；1 小时后的黏附率为 80%，粒径为 109μm。微球能实现超过 12 小时的药物持续释放。药物-聚合物-聚合物比的影响更为显著。通过扫描电子显微镜研究了黏附性微球的形态特征。体外释放试验表明，阿莫西林在 pH 1.2 盐酸中的释放速度略快于 pH 7.8 磷酸盐缓冲液。在口服单剂量或多剂量（多次）给药条件下，将阿莫西林粉末和黏附性微球施用于幽门螺杆菌感染的 Wistar 大鼠，进行体内幽门螺杆菌清除试验。结果表明，阿莫西林黏附性微球的清除效果优于阿莫西林粉末。总之，阿莫西林黏附性微球可延长药物在胃肠道中的驻留时间并增强阿莫西林的稳定性，有助于实现幽门螺杆菌的完全清除。
