IN VITRO AND IN VIVO EVALUATION OF ACECLOFENAC LYOPHILIZED ORALLY DISINTEGRATING TABLETSAbstract
Aceclofenac, a non-steroidal anti- inflammatory drug, with poor solubility and bioavailability was taken as candidate for enhancement of in vitro dissolution and in vivo bioavailability. Development of Aceclofenac orally disintegrating tablet (ODT) using lyophilization technique was adopted. The ODTs were prepared by freeze-drying an aqueous dispersion of Aceclofenac, matrix former, filler (sugar alcohol), and an anti-collapse. The tablets were evaluated compendial (uniformity of weight, uniformity of content, friability, in vitro disintegration time and in vitro dissolution), together with wetting time, in vivo disintegration time, moisture analysis and scanning electron microscopy. The compendial results showed that lyophilized ODTs disintegrated within few seconds and showed significantly faster dissolution rate of Aceclofenac in comparison with commercially available immediate release tablet Aceclofenac tablet (Bristaflam®). In vivo evaluation for the best chosen Aceclofenac ODT formulation (LA#10) was done for determination of the drug pharmacokinetics in comparison with the immediate release tablet Aceclofenac tablet (Bristaflam® 100 mg). A randomized crossover design was adopted in the comparative bioavailability study done on four healthy volunteers. Statistical analysis revealed significant difference between the Bristaflam IR tablet and Aceclofenac ODT (LA#10) regarding the following pharmacokinetic parameters: Cmax, Tmax, t1/2, AUC(0-24), AUC(0-∞) (p < 0.05); while insignificant difference regarding Mean residence time (MRT) (p > 0.05). The relative bioavailability of the Aceclofenac ODT (LA# 10) was 186.12% relative to the IR tablet (Bristaflam®) taken as reference standard.
Mohamed Aly Abd El Aziz Aly El Degwy*, Saydia Tayel, Mohamed A. El-Nabarawi and Randa Tag A. El Rehem
Formulation Section Head, Mepaco Pharmaceutical Company, 141- Street, Ahmed Zaki, Maadi, Cairo, Egypt
23 September, 2011
28 November, 2011
29 January, 2012