Biodegradable Microcapsules: Optimization of Formulation Using Factorial Design

Biodegradable microcapsules of zidovudine (AZT) were prepared using a solvent evaporation technique. The experimental protocol was based on a 4 times 3 factorial design. The effect of volatile organic solvent was examined at four levels: 100/0, 90/10, 80/20, and 70/30 mixtures of dichloromethane with methanol. Poly(lactide/glycolide) copolymer (PLGA 50:50) was used at three levels: 50, 100, and 200 mg mL−1 The efficiency of encapsulation significantly increased with increasing polymer concentration. The four levels of the organic solvent showed no significant effect on the encapsulation. A comparison of the SEM photographs of the twelve batches of the microcapsules showed that the formation of surface pinholes could be avoided by increasing the concentration of the polymer. Higher methanol concentrations (>10%) in the dichloromethane/methanol mixture also significantly changed the surface morphology. No significant rank order correlation was observed between the median particle sizes of the different batches of the microcapsules and the organic solvent or the amount of PLGA. The median particle sizes were between 33 and 193 μm. Particle size ranges were between 0.5 and 600 μm. The initial drug release was between 15 and 50% during the first day with a sustained release observed up to 60 days.