ABSTRACT
A new method of dissolution test was established to better simulate the in vivo dissolution behavior of drugs from preparations and to distinguish the quality difference between drug preparations. With flow-through cell being chosen to be the dissolution apparatus and nimodipine tablet to be the model drugs,this study developed,on the basis of IVIVC theory,a new dissolution method which was subsequently used to evaluate the dissolution con-sistency of domestically produced nimodipine tablet as test preparation and its reference preparation. Meanwhile, conventional four-dissolution-curves method based on paddle apparatus was selected for comparison to evaluate the efficiency of the new dissolution method. The results indicated that the new dissolution method not only had a good correlation with the in vivo process of drugs,but also could reveal the internal quality differences between pharmaceutical preparations effectively. This research will provide further theoretical support for the application of flow-through cell apparatus in IVIVC study.
ABSTRACT
It is generally assumed that study of in vitro dissolution can reveal the in vivo behavior and bioavailability of a drug. The dissolution test indisputably plays a vital role in the research and development of pharmaceutical preparations as well as routine quality control of approved drugs. In order to develop an ideal dissolution method, the physicochemical properties of drug and the characteristics of its dosage form should be considered, and a proper dissolution condition be established to simulate the in vivo dissolution behavior of drugs. The new dissolution method should have the required characteristics of accuracy and durability, but also could distinguish pharmaceutic preparations with different quality. In recent years, there have been more and more reports on the establishment and verification of dissolution methods for oral solid dosage forms. However, there is very few review articles on the topic. According to the latest guidelines by domestic and foreign drug organizations, this review paper is prepared to summarize the most important skills and progress in the development of dissolution methods for oral solid preparations. The aim is to provide a reference for the development and validation of new dissolution methods.
ABSTRACT
Aim To evaluate the correlation between in vitro release and in vivo absorption of azithromycin cat-ionic micron niosomes (ACMNS)by Wagner-Nelson method and deconvolution method. Methods The in vitro release behavior of ACMNS was studied by dy-namic membrane dialysis. After a single dose of intra-gastric administration with ACMNS and AM in rats,the AM concentrations in plasma were determined by high performance liquid chromatography(HPLC). Wagner-Nelson and deconvolution method were used to reveal the in vitro / in vivo correlation. Results X used as cu-mulative in vitro release and Fa as the absorption per-centage,the regression equation was established:F a =3. 0524X - 5. 7709,r = 0. 8976,and X used as cumu-lative in vitro release and R as input function,the re-gression equation was established:R = 2. 3413X -58. 687,r = 0. 5217. r < r( 2,0. 05) = 0. 9500 (P <0. 05). Conclusion There is no correlation between in vitro release and in vivo absorption of ACMNS.
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.