Design and Evaluation of Rapidly Disintegrating Tablets of Racecadotril with Enhanced in-vitro Dissolution Achieved by Solid Dispersion Technique

Racecadotril is an antidiarrheal drug which acts as a peripherally acting enkephalinase inhibitor. It is a solubility limited compound and thus the bioavailability can be improved by increasing its aqueous solubility. Solid dispersions of racecadotril were prepared using polymers beta-cyclodextrin, poloxamer 188 (Lutrol F 68) and poloxamer 407 (Lutrol F127) in different proportions (1:1, 1:3, 1:5 and 1:10). Solvent evaporation method was employed using methanol as solvent. The solid dispersion complexes were also characterized using FT-IR, DSC and XRD. The optimized dispersions were formulated into rapid disintegrating tablets using Kollidon (R) CL-SF and sodium starch glycolate (SSG) as disintegrants with proportion of 2%, 3%, and 4%. The disintegration time, mean dissolution time (MDT), T-50 and T-90 of the formulated tablets were evaluated and compared with the marketed formulation. The pure drug showed aqueous solubility of 18.89 mu g/ml while the solid dispersions with poloxamer 188 and poloxamer 407 in ratios 1:5 showed solubility of 70.75 mu g/ml and 58.07 mu g/ml. There was a 3 fold increase in drug solubility. The disintegration time of all the formulations were found to be less than 42 sec. Both Kollidon (R) CL-SF and SSG decreased the T-50 and T-90 values but Kollidon (R) CL-SF at a concentration of 4% was found to show the best results (T-50 = 10.63 +/- 0.17, T-90 = 35.31 +/- 0.57 and MDT = 13.85 +/- 0.27 min). This was further compared with marketed formulation. The difference (f1) and similarity (f2) factors was found to be 89.91 and 21.11 respectively. The results suggest that the designed formulation is improved than the marketed formulation. The improved solubility, dissolution and drug release may be highly beneficial in improving the overall bioavailability of RDT.