Multi-scale analysis of amorphous solid dispersions prepared by freeze drying of ibuprofen loaded acrylic polymer nanoparticles

Abstract

Amorphous solid dispersions (ASDs) consisting of ibuprofen as a model drug, and Eudragit L100-55 as methacrylate copolymer carrier, were prepared by emulsification-diffusion method followed by freeze drying of nanoparticle suspensions. Subsequently, ibuprofen-loaded Eudragit L100-55 nanoparticles with different drug loadings were prepared. To understand the processing-structure-properties relationships, multi-scale analysis was performed. Average diameter of nanoparticles in all formulations was 234 ± 30 nm. Differential scanning calorimetry, X-ray diffraction and infrared spectroscopy showed that the formulations prepared from 9 to 16% of ibuprofen were fully amorphous while nano-crystalline domains localized inside the polymeric nanoparticles thanks to the atomic force microscopy analysis were detected in formulations prepared from higher content of ibuprofen (≥20%). Unexpected increase of the entrapment efficiency with the increase of ibuprofen loading was correlated with the increase of the viscosity of the organic phase. ASDs exhibited good dissolution profiles, characterized by sustained ibuprofen release, followed by supersaturation build-up. Physical stability tests performed on the ASDs showed that ibuprofen remained amorphous after 12 months of storage period. Therefore, Eudragit L100-55 plays a dual role in the ASDs, i.e. kinetic stabilization of ibuprofen in amorphous state during the storage period, and control of the drug release, and subsequent stabilization of the supersaturated state.