Pharmacokinetics and in vitro-in vivo correlation evaluation of self-emulsifying drug delivery system and conventional tablets of aniracetam / 中国临床药理学与治疗学

ABSTRACT

AIM: To evaluate the correlation between in vitro release and in vivo absorption of aniracetam in conventional tablets and self-emulsifying drug delivery system (SEDDS), to investigate pharmacokinetics of aniracetam self-emulsifying drug delivery system and conventional tablets of aniracetam after oral administration to rats. METHODS: Dissolution behavior of these formulations was evaluated in vitro to assess the properties of dosage forms. And a new RP-HPLC method was developed for the in vivo quantitative determination of 4-p-anisamidobutyric acid (PABA), the active metabolite of aniracetam. To approach the in vitro-in vivo correlation, fraction absorbed in vivo (f) was calculated by Wagner-Nelson method, and then compared with in vitro released drug percentages (Q%). RESULTS: Aniracetam was released rapidly from SEDDS with 80%±4% of accumulation dissolution rate compared to that from conventional tablets at 15 min. The recovery of active metabolite of aniracetam was about 90%, and the intra-days and inter-day precision were within 4% and 6%, respectively. The AUC0-∞ value of aniracetam SEDDS was (11 168±2 395) ng·mL-1·h, which was about 3 folds greater than conventional tablets. The parameter MRT0-∞ of aniracetam SEDDS and conventional tablets were (2.7±0.6) h and (1.7±0.6) h, respectively, and the difference was statistically significant(P<0.05). The linear equation of in vitro-in vivo correlation for conventional tablets was obtained by regression as well. Whereas nonlinear correlation was obtained for aniracetam SEDDS, which fitted the quadric model very well and the correlation coefficient was 0.972. CONCLUSION: Aniracetam can be released faster from SEDDS than that from conventional tablets, and SEDDS improved the bioavailability of aniracetam significantly. The SEDDS composed by oil and compound surfactants which could enhance the absorption showed the expressing rate of dissolution, and those formed the o/w microemulsion with gastrointestinal liquid could absorb through lymphatic transport route.