Hypromellose functionality in film-forming solutions: In vitro characterization and in silico optimization for...

This study investigated the development of hypromellose-based film-forming solutions (FFSs) containing ketoprofen, aiming to elucidate how key formulation variables (concentration and type of hypromellose (high-viscosity grades 2910 and 2208), plasticizers (macrogol 400 and propylene glycol) and volatile solvents (water and water/isopropanol mixtures)) influence FFSs performance and film properties. The FFSs were characterized in terms of pH, transparency, and rheological behavior, while the resulting films were evaluated for weight, stickiness, and mechanical properties. All FFSs exhibited pH values ranging from 4.10 to 5.83, high transparency (transmittance >90%), and shear-thinning behavior. The results demonstrated a critical role of polymer and plasticizer selection, with hypromellose 2910 outperforming hypromellose 2208 in both FFS and film properties, and macrogol 400 yielding films with superior mechanical performance compared to propylene glycol. The performance-defining characteristics and further in silico optimization of plasticizer concentration using a second-order polynomial regression model based on tensile strength, Young's modulus, and elongation at break, enabled identification of an optimal FFS composition (2% hypromellose 2910, 1.52% macrogol 400, 2.5% ketoprofen, and a 1:1 water/isopropanol mixture up to 100%). The optimized formulation formed a transparent film with favorable mechanical properties, including tensile strength (10.94 ± 2.26 MPa), elongation at break (75.97 ± 6.12%), and Young's modulus (33.79 ± 4.76 MPa). In vitro drug release was significantly enhanced from the optimized FFS compared to commercial gels, reaching 82.66% after 6 h and following the Korsmeyer-Peppas model, indicating its potential as a carrier for topical administration of ketoprofen.