The influence of process parameters on the PLA nanoparticle size distribution, evaluated by means of factorial design

Polylactic acid (PLA) nanoparticles containing indomethacin were prepared by interfacial deposition of PLA following acetone displacement from a dichloromethane acetone solution towards an aqueous phase. The manufacturing process was carried out according to a factorial experimental design combined with a multiple regression analysis in an attempt to identify the interactions between the different parameters responsible for nanoparticle formation. Among the different sequential designs chosen only the last 3 k design was able to describe the behaviour of the system and account for the complex nature of the physicochemical phenomena involved in the formation of nanoparticles. The migration speed of the acetone was the most significant parameter in nanoparticle formation affecting mean particle size. The lack of significance of the interactions between acetone and dichloromethane suggested that both solvents behaved independently and acetone was not retained by the dichloromethane in its migration into the aqueous phase. The nanoparticle systems obtained at the various levels of dichloromethane and their mechanism of formation appeared to be different. The mean particle size increased as the dichloromethane level augmented. It was observed that the nanoparticle formation process was very fast and hence the process conditions prevailing immediately after the aqueous and organic phase mixing determined the physicochemical properties of the nanoparticles