Versatility of three techniques for preparing ibuprofen-loaded methacrylic acid copolymer nanoparticles of controlled sizes

Comparative studies of the techniques used for preparing polymeric nanoparticles (NP) are rarely reported in the literature. To gain insight in this field, NP were prepared under different conditions using the salting-out, emulsification-diffusion and nanoprecipitation methods and their properties such as drug loading efficiency, residual poly(vinyl alcohol), thermal behavior and morphological characteristics were investigated. Methacrylic acid copolymer Type C (Eudragit L100-55) and ibuprofen (IBU) were used as polymer and model drug, respectively. The salting-out and emulsification-diffusion methods allowed the preparation of IBU-loaded NP with the mean sizes ranging from 140 to 650 nm. Drug loading efficiency was improved when the NP mean size increased and the aqueous phase pH decreased. Nanoprecipitation allowed production of NP with sub-140 nm mean size. IBU was more effectively incorporated in salting-out-NP than in emulsification-diffusion-NP. Basically, the inherent formulation parameters of the salting-out method - i.e. lower solubility of Eudragit L100-55 in acetone, miscibility of acetone with water and lower volume of water required to induce solvent diffusion - favored the polymer precipitation rate and solvent diffusion rate, promoting drug incorporation into the NP. Nanoprecipitation resulted in poor IBU incorporation into the NP. Differential scanning calorimetry studies revealed that IBU was present in an amorphous or molecularly dispersed state in the NP. Finally, it was observed that residual PVAL was directly proportional to the specific surface area of nanoparticles, as examined for the emulsion-based methods.