Formulation and In Vitro Evaluation of Matrix Tablets Containing Ketoprofen-Beta Cyclodextrin Complex for Enhanced Rheumatoid Arthritis Therapy: Experimental and Computational Insights.

Background: Rheumatoid arthritis is a chronic autoimmune disease that leads to severe disability and requires improved therapeutic strategies to optimize anti-inflammatory treatment. This study aimed to address this challenge by developing and characterizing an extended-release polymer matrix tablet containing ketoprofen and a ketoprofen-β-cyclodextrin complex with enhanced therapeutic properties. The objective was to improve inflammation management and therapeutic outcomes using a novel delivery system based on the inclusion of the active substance in cyclodextrin complexes. Methods: Tablets were formulated using ketoprofen and ketoprofen-β-cyclodextrin complexes combined with hydrophilic polymers such as Carbopol® 971P NF, Kollidon® VA 64, and MethocelTM K4M. The complexes were obtained via the coprecipitation method to improve bioavailability. The kinetics of the release of ketoprofen, ketoprofen-β-cyclodextrin complex (2:1), and ketoprofen-β-cyclodextrin complex (1:1) from the tablets were investigated in vitro in artificial gastric and intestinal fluids, and drug release profiles were established. Advanced mathematical models were used to describe the nonlinear behavior of the drug-polymer systems. Results: The inclusion of ketoprofen in the β-cyclodextrin complexes was confirmed, revealing distinct release profiles. Tablets (K-3 F-3) containing the 1:1 complex showed rapid release (96.2% in 4-7 h), while tablets (K-1 F-4) containing free ketoprofen released 76% over 9-11 h. Higher polymer concentrations slowed the release due to gel barrier formation. Pharmacotechnical and stability tests supported their suitability as extended-release forms. A multifractal modeling approach described the release dynamics, treating the polymer-drug matrix as a complex system, with release curves characterized by variations in the fractal dimension and resolution. Conclusions: Specific hydrophilic polymer combinations effectively prolonged ketoprofen release. The developed matrix tablets, which were evaluated via in vitro studies and mathematical modeling, show promise for improving therapeutic outcomes and patient compliance during rheumatoid arthritis treatment.