摘要
以三脉冲阿莫西林缓释片Moxatag~(775 mg)为参比制剂,采用湿法制粒工艺制备脉冲(1)胃溶颗粒,挤出滚圆工艺制备高载药量丸芯、流化床包衣技术制备脉冲(2)和脉冲(3)肠溶微丸。以药物累积释放率为考察指标,采用单因素法优化了含药丸芯组成、脉冲(2)微丸肠溶包衣层中增塑剂的用量、脉冲(2)和脉冲(3)微丸肠溶包衣层增重及固化条件。将含药量分别相当于整片剂量(775 mg)45%、30%及25%的脉冲(1)胃溶颗粒、脉冲(2)和脉冲(3)肠溶微丸以及适量辅料混匀,采用直接法压片,再外包胃溶型衣制得自制缓释片。采用相似因子(f_2)法评价了自制缓释片与Moxatag~释放曲线的相似性。结果表明,含药丸芯优选低取代羟丙纤维素作为成丸促进剂;采用Eudragit L30D-55,在增重20%、包衣液中增塑剂枸橼酸三乙酯占干聚合物量30%的条件下,能制得在pH 4.0介质中2 h基本不释药、在pH 6.0介质中15 min释药大于80%的脉冲(2)微丸;采用易信克肠溶型薄膜包衣预混剂,在增重40%的条件下,能制得在pH 6.0介质中2 h基本不释药、在pH 6.8介质中15 min释药大于80%的脉冲(3)微丸。所得自制缓释片与Moxatag~释放曲线相似,提示二者体外释药行为一致。
Based on the formulation of tripulse extended-release tablets Moxatag （containing amoxicillin 775 mg）, the pulse （1） gastric soluble granules were prepared by wet granulation technology, and the pulse （2） and pulse （3） enteric-coated pellets were prepared by fluidized bed coating with the high drug-loading cores obtained by extrusion- spheronization technology. The composition of drug-loading cores, the amount of plasticizer （triethyl citrate, TEC） in the enteric coating layer of pulse （2） pellets, the weight gain and curing condition of enteric coating layer of pulse （2） and pulse （3） pellets were optimized by single factor test with the cumulative release as the index. The uniform mixture of pulse （1） granules, pulse （2） and pulse （3） pellets in which the content of amoxicillin were separately equivalent to 45 %, 30 %, and 25 % of 775 mg and suitable excipients were compressed into tablets, then coated with Opadry （gastric） to produce the final product. The similarity of release profiles between the final product and Moxatag was evaluated by the similarity factor （f2） method. The results showed that the drug-loading cores was preferably chosen low-substituted hydroxypropyl cellulose as the pellet-forming enhancer. The pulse （2） pellets had no drug release basically at 2 h in pH 4.0 phosphate buffer, and more than 80% release at 15 rain in pH 6.0 phosphate buffer, when Eudragit L30D-55 was chosen as the enteric material, in which the amount of plasticizer was at least 30% of dry polymer content, and with weight gain of 20%. The pulse （3） pellets had no drug release basically at 2 h in pH 6.0 phosphate buffer, and more than 80% release at 15 rain in pH 6.8 phosphate buffer, when Eascol EOBS68 was chosen as the enteric material and with weight gain of 40 %. The release curve of the resulting pulsatile extended-release tablets was similar to the commercially available tablets （Moxatag ）, indicating the in vitro release of both were consistent. In sel
作者
张雯
陈超
赵爱丽
闫志猛
ZHANG Wen;CHEN Chao;ZHAO Aili;YAN Zhimeng(Shandong Provincial Engineering Research Center./br Sustained-release Preparation of Chemical Drugs Shandong Academy of Pharmaceutical Sciences, Jinan 250101)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2018年第5期622-629,共8页
Chinese Journal of Pharmaceuticals
关键词
阿莫西林
多脉冲
胃溶颗粒
肠溶微丸
微丸压片
释放度
amoxicillin
multi-pulse
gastric soluble granule
enteric-coated pellet
pellet tableting
release
