Formulation and optimization of tramadol loaded alginate beads using response surface methodology

Tramadol loaded alginate beads were formulated by ionic cross-linking technique employing calcium chloride as cross-linking agent. Several parameters like bead size, swelling index, incorporation efficiency, in vitro release and in vivo drug activity studies were investigated. Tramadol loading and concentration of calcium chloride were found to have a significant effect on the selected parameters. Tramadol release decreased with decreasing drug loading and increasing concentration of cross-linking agent. Kinetic modeling indicates the involvement of both swelling and erosion on the release characteristics of the drug from the beads. A 2 factors-3 levels central composite design (CCD) was employed to evaluate the effect of critical formulation variables, namely drug loading (X1) and concentration of calcium chloride (X2) on various responses. Multiple linear regression analysis generated polynomial mathematical models for various response variables and the corresponding response surface and contour plots were drawn. X1 was found to have more significant effect than X2 on the dependent variables. In vivo drug activity studies of the alginate beads demonstrated significant antinociceptive effect of tramadol.