Preparation and evaluation of zidovudine-loaded sustained-release microspheres. 2. Optimization of multiple response variables.

The formulation of zidovudine-loaded (AZT-loaded) sustained-release microspheres was prepared and optimized using response surface methodology. The objective was to use this statistical procedure to obtain a formulation with optimized overall properties. The effect of formulation variables (emulsifier concentration, drug to polymer ratio, and composition of the internal phase of the emulsion) on a number of response variables was systemically investigated. The response variables were t85, entrapment efficiency, yield, and percentage of loose surface crystals. A desirability function that combines these four response variables was constructed. A second-order polynomial equation was fitted to the data, and the resulting equation was used to predict the responses in the optimal region. All the investigated response variable were found to be highly dependent on the formulation variables, with strong interactions observed between the formulation variables. It was found that optimum overall desirability of AZT microspheres can be obtained at low levels of SDS and ethyl acetate concentrations and at intermediate levels of drug to polymer ratio. An optimized formulation was prepared under these experimental conditions and evaluated for individual responses and overall desirability. The experimental values of the response variables highly agreed with the predicted values.