(283f) A Novel Approach for Transformation of Nanosuspensions Into Polymer Films Containing Nanoparticles

In this work, the feasibility of a simple, continuous process of incorporating stable nanoparticles into edible polymer films was examined. The final goal of this work was to enhance the dissolution rate of poorly water soluble drugs by preserving the particle size after film disintegration. Nanosuspensions produced from wet stirred media milling (WSMM) were transformed into polymer films containing drug nanoparticles by mixing with a low molecular weight hydroxylpropyl methyl cellulose (HPMC E15LV) solution containing glycerin followed by film casting and drying in an oven; both with or without the use of convective drying.  Three different BCS Class II drugs, naproxen (NPX), fenofibrate (FNB) and griseofulvin (GF) were studied.  Drug particle size was obtained by using laser diffraction.  Drug crystallinity was studied by XRD and Raman spectroscopy.  Particle dispersion in polymer films was studied by using SEM and NIR chemical imaging. Film mechanical properties were studied by using a texture analyzer.  Drug content was studied by HPLC. Dissolution was also studied by using a USP IV apparatus. When convective drying was employed, dried films were obtained within 60 minutes or less depending on the drying conditions. The drying rates increased with an increase in temperature and airflow rate. A two stage drying process was observed, a linear behavior (stage I) followed by a nonlinear behavior of drying (stage II). It was shown that film processing methodology employed has no effect on the drug crystallinity.  NPX exhibited the strongest aggregation compared to the other drugs.  The aggregation had a direct effect on drug content uniformity in the film. Due to strong hydrogen bonding with the polymer, NPX exhibited an increase in Young’s Modulus (YM) of approximately 200%, among other mechanical properties, compared to GF films.  A synergistic effect between surfactant/polymer and drug/polymer interactions in the FNB film resulted in an increase of more than 600 % in YM compared to the GF film. NPX also exhibit the stronger aggregation and less uniform drug content in films.  A faster dissolution rate was also observed for films containing nanoparticles compared to films containing microparticles and other solid dosage forms with similar formulation. These results set the foundation for continuously operating process development of films containing nanoparticles, specifically, for poorly water-soluble drugs, for various drug delivery applications.  As compared to various routes to making solid dosage forms from drug nanosuspensions such as freeze drying, lyophilization, and spray drying, film formation may offer a more economical and scalable option.