【摘要】：目的:制備帕利哌酮緩釋片,并對其在Beagle犬體內(nèi)的藥動學(xué)進(jìn)行評價(jià)。方法:首先制備含有帕利哌酮的緩釋片芯,再將其通過壓制包衣的手段包埋在同樣含有帕利哌酮的緩釋材料中,壓片制得。采用單因素試驗(yàn)和星點(diǎn)設(shè)計(jì)-效應(yīng)面法,以自研緩釋片和原研制劑(芮達(dá)~汶)在pH6.8磷酸鹽緩沖液(PBS)中釋放行為的相似性為評價(jià)指標(biāo),優(yōu)化自制緩釋片的處方;以Beagle犬為模型,考察了自制緩釋片和原研制劑的體內(nèi)藥動學(xué)行為,采用液-質(zhì)聯(lián)用(LC-MS/MS)法測定血漿中帕利哌酮濃度,并采用非房室模型計(jì)算兩制劑的藥動學(xué)參數(shù)。結(jié)果:優(yōu)化后的自制緩釋片與原研制劑在pH6.8磷酸鹽緩沖液中的釋放行為相似(相似因子大于50),自研緩釋片與原研制劑的Cmax為(76.79±67.88)ng·mL-1和(76.86±59.80)ng·mL-1,AUC(0→∞)為(1 643.92±1 307.79)ng·mL-1·h和(1 652.33±1 249.45)ng·mL-1·h,提示兩制劑相似。結(jié)論:通過壓制包衣制備帕利哌酮緩釋片可實(shí)現(xiàn)與原研制劑(芮達(dá)~汶)達(dá)到一致的目的。
[Abstract]:Aim: to prepare Pariperidone sustained-release tablets and evaluate its pharmacokinetics in Beagle dogs. Methods: firstly, the sustained release tablets containing Pariperidone were prepared, and then the tablets were prepared by pressing and embedding them in the same sustained-release materials containing Pariperidone. Single factor test and star design-effect surface method were used to optimize the formulation of self-made sustained-release tablets based on the similarity of release behavior between the self-developed sustained-release tablets and the original preparation (Ruida Wen) in pH6.8 phosphate buffer (PBS). The pharmacokinetic behavior of sustained release tablets and probiotics in Beagle dogs was investigated. The plasma concentration of peridol was determined by liquid-mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters of the two preparations were calculated by non-atrioventricular model. Results: the release behavior of the optimized sustained-release tablets was similar to that of the original preparation in pH6.8 phosphate buffer (similarity factor > 50). The Cmax of self-made sustained-release tablets and original preparations were (76.79 鹵67.88) ng mL-1 and (76.86 鹵59.80) ng mL-1,. AUC (0 ~ 鈭，

本文編號：2403869