Formulation and Evaluation of Propolis Solid Dispersion Loaded Anti-inflammatory Cream with Molecular Docking and In-Vivo Animal Study

Purpose Propolis, a bioactive resinous substance produced by bees, is renowned for its anti-inflammatory and wound-healing properties. However, its poor aqueous solubility restricts its therapeutic potential in topical applications. This study aims to enhance the solubility and anti-inflammatory efficacy of propolis by formulating it into a solid dispersion (SD) using Kollisolv PEG-8000. Methods: Solid dispersions of propolis were prepared via the melting method using Kollisolv PEG-8000 in a 1:2 ratio. Optimization of two independent variables was achieved through central composite design. The optimized SD was incorporated into a topical cream using the fusion method. Molecular docking studies were conducted to assess the interaction of key propolis constituents—quercetin, gallic acid, and galangin—with TNF-α, supporting their anti-inflammatory potential. Results: The optimized formulation exhibited a drug release of 98.7%, viscosity of 35,786 cPs, and spreadability of 16.82 cm/s, alongside a 340-fold increase in aqueous solubility. In vivo evaluation using a carrageenan-induced paw edema model in rats demonstrated significant anti-inflammatory activity and TNF-suppression, comparable to diclofenac gel. Molecular docking confirmed strong binding affinities of the selected flavonoids with TNF-α, reinforcing the formulation’s mechanistic relevance. Conclusion: Solid dispersion technology effectively enhances the solubility and therapeutic performance of propolis. The integration of molecular docking substantiates its anti-inflammatory mechanism, positioning SD-based propolis cream as a promising natural alternative for topical inflammatory conditions.