山楂叶总黄酮自微乳化膜控释滴丸的研究

Study on self-microemulsifying membrane controlled-release drop pill of hawthorn leaves flavonoids

制备山楂叶总黄酮自微乳化膜控释包衣滴丸,并对其进行体内外的相关性研究。采用自微乳化技术,将水溶性较差的山楂叶总黄酮制备成水溶性较好的山楂叶总黄酮自微乳液,解决山楂叶总黄酮溶解性问题。采用聚乙二醇6000作为基质,将山楂叶总黄酮自微乳液固化成滴丸,采用包衣技术制备成山楂叶总黄酮自微乳化膜控释包衣滴丸。对山楂叶总黄酮自微乳化膜控释滴丸进行体外释放度的研究,进行SD大鼠体内药动学的研究。山楂叶总黄酮自微乳化滴丸处方为0.25 g山楂叶总黄酮,0.25 g肉豆寇酸异丙酯,0.375 g聚乙二醇400,0.375 g cremophor RH 40,2 g聚乙二醇6000。包衣优化处方为4 g乙基纤维素20,0.64 g聚乙二醇400,1.8 g邻苯二甲酸二乙酯,3.5%包衣增重。山楂叶总黄酮自微乳化膜控释包衣滴丸在体外释放及大鼠体内药动学参数符合12 h缓控释制剂的设计,而且缓控释滴丸的生物利用度是速释滴丸的2.47倍。通过自微乳化及包衣技术可以将难溶性药物山楂叶总黄酮制备成缓控释制剂。

To prepare the hawthorn leaves flavonoids self-microemulsifying membrane controlled-release coated drop pill, and to study its release rate in vitro and pharmacokinetics study in vivo. In order to improve the dissolntion of hawthorn leaves flavonoids, self-microemulsifying technology was used to prepare the hawthorn leaves flavonoids self-mieroemulsion. Hawthorn leaves flavonoids self-microemulsifying drop pill was prepared with the PEG 6000. Studies were made on the in vitro release of flavonoids from hawthorn leaves self-micro-emulsifying membrane-moderated coated drop pills and the in vivo pharmaeokinetic in rats. The prescription of fla- vonoids from hawthorn leaves self-micro-emulsifying drop pills was 0. 25 g of flavonoids from hawthorn leaves, 0. 25 g of iodophenyl ma- leimide, 0. 375 g of polyethylene glycol 400, 0. 375 g of eremophor RH 40 and 2 g of polyethylene glycol 6000. The optimized pre- scription was 4 g of ethyl cellulose 20, 0. 64 g of polyethylene glycol 400, 1.8 g of diethyl phthalate, and the weight of coating materi- als increased by 3.5%. Flavonoids from hawthorn leaves self-micro-emulsifying membrane-moderated coated drop pills complied with the design of sustained-release in 12 h in terms of in vitro release and in vivo pharmacokinetic parameters in rats, and its bioavailability was 2.47 times of quick-release drop pills. Slightly soluble flavonoids from hawthorn leaves could be made into sustained-release prepa- rations by the self-micro-emulsifying and coating technology.