Abstract:

The preparation and characterization of a new dosage forms for improving the dissolution of insoluble drug carvedilol were developed. The carvedilol dropping pills were prepared by solid dispersion technique. The response surface methodology was used to select and verify the optimal preparation process. The dissolution rate in vitro were investigated between self-made dropping pills in four mediums. The drug existing state in dropping pills was identified by DSC，IR spectroscopy，and X-ray diffraction. The results show that the optimal preparation process are as follows: the ratio of drug and matrix is 1∶7, the ratio of PEG6000 and PEG4000 is 1∶3, the drug solution temperature is 75℃, dropping speed is 54min^-1. The dissolution rate in vitro is fastest within 30min in the hydrochloric acid solution of pH1.2, reaching over 90%, followed by pH4.5, pH6.8 and deionized water. The dissolution rate in vitro of three batch dropping pills have similarity（f₂ >85）, which show the stability of the optimal process. The presence state of drugs in dropping pills is mainly amorphous, which can improve the dissolution of insoluble drugs and provide important reference for the development of new oral rapid release dosage forms of carvedilol.

Key words: carvedilol, dropping pill, response surface methodology, dissolution rate, characterization

摘要：

本文开发了一种可提高新剂型的可提高难溶性药物卡维地洛溶出的制备方法并进行表征。采用固体分散技术法制备滴丸，通过响应面试验法，按照归一值法优化指标，优选最佳工艺并验证，考察自制滴丸体外溶出度。采用差示扫描量热法（DSC）、粉末 X射线衍射法和红外吸收光谱法鉴定药物在滴丸中的存在状态。结果表明：最优制备工艺为卡维地洛与基质质量比为1∶7，PEG6000与PEG4000质量比为1∶3，滴速为54min^-1，药液温度为75℃，所建模型显著。滴丸在pH1.2的盐酸溶液中30min内释药最快，达到90%以上，其次为pH4.5、pH6.8、去离子水。所制3批滴丸重现性好，体外溶出相似（f ₂>85），稳定性好。药物在滴丸中主要以无定形状态存在，可提高难溶性药物的溶出，为卡维地洛新的口服速释剂型的开发提供参考。

关键词: 卡维地洛, 滴丸, 响应面, 溶出度, 表征