Study on increasing the solubility and dissolution rate of sulfamethoxazole by cyclodextrins

Abstract

The aim of this study was to enhance the solubility and the dissolution rate of sulfamethoxazole (SMZ) by preparing the inclusion complexes with β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HPβ-CD), and γ-cyclodextrin (γ-CD). Selection of an appropriate complexing agent and the method of formulation are critical. The effect of the type of cyclodextrins used for the preparation of complexes, on the in vitro dissolution profiles and solubilities in different mediums (pH 4.5 and pH 7.0) was also evaluated. The interaction between SMZ and cyclodextrins in solution was studied by the phase-solubility method. Inclusion complexation was confirmed by the results from the studies of infrared spectoroscopy (IR) and differential scanning calorimetry (DSC). The effect of water-soluble polymers i.e., polyethylene glycols 4000, 10000, 20000 and non-ionic surfactants i.e., polysorbate 20, 40, 60 on the complexation of SMZ with CDs were also investigated by the same methods. The rates of release of the active material from the complexes were determined from dissolution studies using USP XXII paddle method. As a result of this study, it was found that the solubility of SMZ was significantly enhanced by inclusion of β-CD especially when the water soluble additives are added (from 0.086mg mL-1 to 0.377mg mL-1 with SMZ:β-CD:PEG20000). Thus, it was thought that the bioavailability of SMZ could be increased.