AbstractsChemistry

The objective of the present study was to show the potential of a water soluble vitamin, Pyridoxine HCl (Pyd) to be used as a pharmaceutical adjuvant in order to increase the solubility and dissolution of BCS Class II dug Spironolactone (Spl). Beta-cyclodextrin (ß-CD) was used as the principle carrier. The binary solid dispersion (SD) of ß-CD and Spl in the ratio of 1:1 (SD01) and 1:2 (SD02) along with their respective physical mixtures (PM01 and PM02) were obtained and ternary solid dispersions having ß-CD, Spl and Pyd in the ratio of 1:1:1 (SD03) and 1:2:1 (SD04) along with their respective physical mixture (PM03 and PM04) were prepared by using the solvent evaporation method. In the ternary solid dispersion system (SD04), Pyd as the adjuvant showed synergism along with the hydrophilic ß-CD to enhance the solubility and dissolution of the drug Spl as compared to the binary systems. The SD04 showed a maximum extent of increase in solubility of 362.71± 3.6 µgm/mL as compared to the pure Spl alone at 34.48 ± 1.69 µgm/mL. Drug content in all the SDs was uniform with the lowest being 93.14 ± 3.2% and the highest was 94 ± 2.8%. Solid state characterization, including DSC, FTIR and PXRD, was performed which indicated that the presence of Pyd, facilitated the formation of an inclusion complex. Inclusion complex formation is considered as the prime mechanism for the enhancement of solubility and dissolution of the drug spironolactone. In-vitro dissolution testing indicated that SD04 showed the maximum drug release of 84.21± 6.3% over the period of time above all the binary SDs, PMs and pure Spl. Evaluation of the dissolution profiles showed that all the systems primarily followed Higuchi Kinetics. Thus, Pyd was found to be efficient as an adjuvant in order to increase the solubility of the BCS Class II model drug spironolactone when formulated in a ternary solid dispersion along with the ß-CD.