Simvastatin (SMV) is a well-known antihyperlipidemic drug that has demonstrated wound healing effects. However, its clinical application is hindered by poor solubility. Therefore, the objective of this study was to enhance the solubility of simvastatin by utilizing various concentrations of solvents and co-solvents for formulation in selected topical dosage forms. Mixed-solvent systems, namely Buffer-methanol, Buffer-ethanol, and Buffer-dmso, were employed. Additionally, the impact of different polymer concentrations, including carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), and chitosan (CHT), on drug solubility was investigated.The solubility profile of SMV in 2% w/v polymeric solutions (CMC, HPMC, and CHT) was found to be 73.5, 62.1, and 59.6 µg/ml, respectively. Notably, the use of a 2% w/v chitosan solution resulted in a remarkable 50-fold increase (73.5 µg/ml) in SMV dissolution compared to its aqueous solubility (1.45 µg/ml). This significant enhancement allows for the incorporation of large amounts of the drug in formulations.Our findings indicate that the Chitosan system with ethanol exhibited the highest solubilization effect and demonstrated the necessary characteristics for the preparation and handling of wound dressing films. This suggests a promising approach for the development of topical formulations with improved solubility and potential therapeutic benefits of simvastatin.