Preparation of Poly(D,L-Lactide/Glycolide) Nanoparticles of Controlled Particle Size Distribution: Application of Experimental Designs

Abstract

This study investigates the use of the solvent evaporation method for preparing acid and glycolic acid-based copolymer nanoparticles. Initially, appropriate technological and formulation factors for elaboration of polymeric particles were selected by screening. Most favourable results were obtained using polyvinyl alcohol as a dispersing agent and a high pressure homogenizer to reduce the droplet size of the emulsion initially formed. On the basis of the conclusion thus drawn, a composite rotational experimental design was employed to evaluate the joint influence of three formulation variables (phase volume ratio of the emulsion formed, polymer concentration and homogenization pressure) on the micromeritic properties of the suspension finally obtained (mean particle size, coefficient of variation and polydispersity of the particle size distribution). Analysis of variance corresponding to the experimental design, showed a significant influence of the volume phase ratio and the polymer concentration on the mean particle size and the coefficient of variation, whereas the polydispersity is also affected by the homogenization pressure. Considering this information, a 3² experimental factorial design was then selected to investigate the possible interaction between the phase volume ratio and the concentration of polyvinyl alcohol in the aqueous phase. Analysis of variance and subsequent sequencial regression analysis evidenced last hypothesis providing the way to determine the experimental conditions required to achieve a specific particle size distribution.