(44a) Maximizing Poorly Water-Soluble API Nanoparticle Loading in Polymer Strip Films

One of the most prevalent misconceptions of the polymer strip film format for pharmaceutical applications is its limited active pharmaceutical ingredient (API) loading. While this is partially due to the size restriction of a typical orodispersible dosage (~6 cm² and ~40 µm thick), this limitation also stems from API particle stability issues in traditional pharmaceutical film manufacturing processes. For instance, solvent casting imposes an inherent limit on the API loading in the resulting film, as exceeding a certain API loading leads to uncontrollable precipitation of API particles upon removal of organic solvent during drying. The objective of this work was to challenge the previously conceived limits of API loading in pharmaceutical strip films using a combination of API nanomilling and slurry casting, as well as evaluate the practical limitations of strip films with high loadings of API nanoparticles. Hydroxypropyl methylcellulose (HPMC) was used as the film-forming polymer and griseofulvin (GF) was used as a model BCS class II API. HPMC-E15 films were prepared with API loadings between 9â??49 wt% GF and HPMC-E4M films were prepared with API loadings between 30â??73 wt% GF. All HPMC-E15 films exhibited good content uniformity and API nanoparticle redispersibility, whereas HPMC-E4M films had slightly worse content uniformity and poor API nanoparticle redispersibility above 50 wt% GF loading. Although film strength remained strong with increasing GF loading, a significant decrease in percent elongation was observed, resulting in film brittleness. Results demonstrate that, with proper particle engineering and stabilization protocols, high loading of poorly water-soluble API nanoparticles is indeed achievable in polymer films.