PREPARATION AND EVALUATION OF SIMVASTATIN ORODISPERSIBLE TABLETS CONTAINING SOY POLYSACCHARIDE AND POTASSIUM POLACRILLIN AS NOVEL SUPERDISINTEGRANTS

Oral bioavailability of Simvastatin is very low (5%) due to bad solubility and effect of first pass. The aim of this work is to enhance its solubility and reformulating it as orodispersible tablet to overcome the two problems. Simvastatin solid dispersions in β- cyclodextrin, hydroxylpropyl-β-cyclodextrin, and hydroxylbutyl-β-cyclodextrin were prepared in different drug: polymer ratios namely 1:1, 1:2, and 1:3 by kneading and solvent evaporation methods. Solid dispersion formation and mixture compatibility was investigated by DSC and FTIR. Based on the results of solubility studies; the best solid dispersion formula was selected and formulated into orodispersible tablet using Emcosoy, K-polacrillin as novel superdisintegrants and mannitol, Pullulan as water soluble diluents and evaluated. The results showed that the increase in drug solubility was dependent on polymer type, concentration and also was affected by preparation method. Simvastatin-hydroxyl-butyl-β-cyclodextrin solid dispersion mixture prepared in 1:2 drug: polymer ratio by solvent evaporation method had a higher solubility. Orodispersible tablet formula prepared by Emcosoy as superdisintegrant, Pullulan as diluent showed least wetting and disintegration times (20 and 35 seconds respectively), faster water absorption rate (82), and the highest dissolution rate where the percentage of drug release reached 100% after 20 minutes.. In conclusion: Orodispersible tablets prepared by Emcosoy as superdisintegrant and pullulan as diluent containing simvastatin-hydroxybutyl-β-cyclodextrin is the best choice to improve its water solubility and hence its bioavailability