Effect of porosity on the release kinetics of propafenone-loaded PEG-g-PLA nanoparticles

Nanoparticle preparation by the emulsification-solvent evaporation method is a complex phenomenon. Various formulation factors can affect the internal structure and release of drug from nanoparticles (NPs). The aim of the present study is to optimize NPs of PEG-g-PLA polymer and study the effect of various factors on the porosity as well as release profile of drug-loaded NPs. Propafenone hydrochloride (Prop.HCl), a model drug, was encapsulated in NPs using different amounts of triethylamine (TEA) and initial drug loading levels. NPs were also prepared without TEA by using propafenone base (Prop). All the formulations were characterized for surface morphology, size and size distribution, encapsulation efficiency, thermal analysis, porosimetry and in vitro release studies. Encapsulation efficiency of Prop ranged between 10% and 43% and was dependent on initial drug loading as well as amount of TEA added. Porosity studies revealed different pore size distribution (PSD) for formulations with and without TEA. Formulations with higher drug loading showed greater volume contribution of small pores, higher fractal dimension suggesting more complex pore structure and slower drug release, probably due to decrease in the effective diffusion coefficient of Prop. Results suggest that formulation factors play an important role affecting the porosity and release rate of NPs. Also, fractal dimension could be one of the most important factors in determining the release behavior of NPs. (c) 2005 Elsevier B.V All rights reserved.