IN VITRO AND IN VIVO EVALUATION OF DICLOFENAC POTASSIUM LYOPHILIZED ORALLY DISINTEGRATING TABLETSAbstract
Diclofenac Potassium, a sparingly soluble non-steroidal anti-inflammatory drug, was taken as candidate for decreasing the onset of action time and increasing its bioavailability by overcoming its first pass metabolism. Diclofenac Potassium orally disintegrating tablet (ODT) formulations were developed using lyophilization technique. The freeze dried tablet formulations were prepared by freeze-drying an aqueous solution of Diclofenac Potassium, matrix former, filler, and an anti-collapse. The tablets were evaluated from both compendial and non-compendial criteria (i.e. uniformity of weight, uniformity of content, friability, in vitro disintegration time, in vitro dissolution, wetting time, in vivo disintegration time, moisture analysis and scanning electron microscopy. The best formula results showed that lyophilized ODT disintegrated within few seconds and showed significantly faster in-vitro dissolution rate of Diclofenac Potassium in comparison with commercially available immediate release tablet Diclofenac Potassium tablet (Cataflam®). The in-vivo evaluation for the best formulation (LD#11) was performed in comparison with the immediate release tablet Diclofenac Potassium tablet (Cataflam® 50 mg). A randomized crossover design was adopted in the comparative bioavailability study and was done on a sample of four healthy human volunteers. Statistical analysis revealed significant difference between the Cataflam immediate release tablet and Diclofenac Potassium ODT (LD#11) regarding the following pharmacokinetic parameters: Cmax and Tmax (p < 0.05); while insignificant difference regarding t1/2, AUC(0-24), AUC(0-∞), and mean residence time (MRT) (p > 0.05). The relative bioavailability of the Diclofenac Potassium ODT (LD# 11) was 101.09% relative to the immediate release tablet (Cataflam®) taken as reference product. Though a significant decrease in the time of onset of action; however no significant increase in the relative bioavailability was observed.
Mohamed Aly Abd El Aziz Aly El Degwy*, Saadia Tayel , Mohamed A. El-Nabarawi and Randa Tag A. El Rehem
Formulation Section Head, Mepaco Pharmaceutical Company 1, El Sharkia, Egypt
05 September, 2012
22 December, 2012
29 December, 2012
01 January, 2013