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采用流化床底喷包衣工艺制备含盐酸普拉克索的两种膜控小丸,分别达到速释和缓释目的,再将其按一定比例混合后制备成盐酸普拉克索双相缓释胶囊。采用单因素试验和星点设计-效应面法,以自研胶囊和原研制剂(Siforl)在pH 6.8磷酸盐缓冲液(PBS)中释放行为的相似性为评价指标,优化了自制胶囊的处方。验证试验表明,优化后的自制胶囊与原研制剂在pH 6.8磷酸盐缓冲液(未经历或经历在pH 1.2盐酸中释放1或2 h)中的释放行为相似(相似因子均大于50)。以Beagle犬为模型,考察了自制胶囊和原研制剂的体内药动学行为。采用LC-MS/MS法测定血浆中盐酸普拉克索浓度,并采用非房室模型计算两制剂的药动学参数。结果表明,自研双相缓释胶囊与原研制剂的c_(max)为(1 118.3±121.9)和(1 108.6±183.2)pg/ml,AUC_(0→∞)为(18 227.5±1 870.8)和(16 321.8±2 327.5)pg·ml~(-1)·h,提示两制剂相似。
The two membrane-coated pellets containing pramipexole hydrochloride were prepared by fluidized bed bottom spray coating process, respectively, to achieve immediate and sustained release purposes, and then mixed in a certain ratio to prepare a pramipexole hydrochloride biphasic sustained-release capsule . The single factor test and the apical design-response surface method were used to optimize the formulation of home-made capsules based on the similarity of release behavior of self-made capsules and Siforl in pH 6.8 phosphate buffered saline (PBS). Validation experiments showed that the optimized self-made capsules showed similar release behavior (similarity factor greater than 50) in pH 6.8 phosphate buffered saline without experiencing or experiencing release of 1 or 2 h in pH 1.2 HCl. Taking Beagle dogs as model, the in vivo pharmacokinetics of self-made capsules and original preparations were investigated. The concentration of pramipexole hydrochloride in plasma was determined by LC-MS / MS and the pharmacokinetic parameters of the two preparations were calculated by non-compartmental model. The results showed that the c max values of the self-developed two-phase sustained-release capsules and the original formulation were (1 118.3 ± 121.9) and (1 108.6 ± 183.2) pg / ml and the AUC 0 0 ∞ was 18 227.5 ± 1 870.8 And (16 321.8 ± 2 327.5) pg · ml -1 h, suggesting that the two preparations were similar.