FORMULATION AND PHYSICOCHEMICAL CHARACTERIZATION OF SODIUM CARBOXY METHYL CELLULOSE AND β CYCLODEXTRIN MEDIATED TERNARY INCLUSION COMPLEXES OF SILYMARIN

The objective of the present investigation was to study the complexation of silymarin, a poorly water soluble herbal drug, with β-cyclodextrin alone and in the presence of sodium carboxymethyl cellulose to evaluate the feasibility of enhancing the solubility and dissolution rate of silymarine. Phase solubility study and kneading method was employed to develop and formulate solid inclusion complexes. Solid inclusion complexes of silymarin –β-cyclodextrin in 1:1 molar ratio were prepared with and without carboxymethyl cellulose by kneading method. Obtained binary and ternary complexes were evaluated for solubility dissolution and physical nature by FTIR, XRD and NMR. The aqueous solubility of silymarin was linearly increased as a function of the concentration of β-cyclodextrin alone and in the presence of sodium carboxymethyl cellulose. Beta cyclodextrin formed binary molecular inclusion complexes with silymarin in1:1 molar ratio as revealed by phase solubility diagram. Sodium carboxymethyl cellulose in ternary complexes has resulted in 2.37 and 1.66 fold enhancements in complexation and solubilizing efficiencies of β-cyclodextrin respectively. Dissolution rate of silymarin in binary and ternary complexes was enhanced up to 1.3 and 1.6 folds respectively when compared with pure silymarin. It is evident that addition of sodium carboxymethyl cellulose affects the complexation and solubilizing efficiencies of β-cyclodextrin hence it may be used in solid dispersions to minimize the overall formulation bulk.