Design and development of modified-release lupeol tablets: Phytosome and chemical derivatization strategies for dissolution behavior enhancement

Abstract

Background: Lupeol is a natural pentacyclic triterpenoid with relevant pharmacological activities; however, its pharmaceutical development is limited by extremely low aqueous solubility. In the present work, formulation strategies were explored to modulate the in vitro dissolution behavior of lupeol in modified-release tablets.Methods: Lupeol, lupeol acetate, and a lupeol–phosphatidylcholine complex were prepared and structurally characterized by NMR spectroscopy. Tablets were produced by direct compression using a hydrophilic coprocessed excipient. Pre-compression properties, tablet quality attributes, and in vitro dissolution profiles were evaluated. Additionally, the similarity factor (f2) was calculated, and the kinetic modeling was analyzed.Results: All formulations met pharmacopeial requirements for weight uniformity, friability, and mechanical integrity. Distinct dissolution profiles were observed depending on the chemical form of lupeol, with the phytosomal system exhibiting faster and more efficient dissolution, while lupeol acetate showed the most retarded release.Conclusion: Chemical derivatization and phospholipid complexation significantly modulated the dissolution behavior of lupeol in hydrophilic matrix tablets. The results support these strategies as formulation tools to tailor release performance of highly lipophilic triterpenoids.