Application of Hansen Solubility Parameters to Improve Oral Absorption of Nintedanib by a Self- Micro-Emulsifying Drug Delivery System

Abstract

Nintedanib is a drug used to treat Idiopathic Pulmonary Fibrosis, but it has poor solubility and low oral bioavailability. This study explored how a Self-Microemulsifying Drug Delivery System (SMEDDS) could improve these issues. By using Hansen Solubility Parameters, two solvents, Benzyl Alcohol and Eugenol, were found to dissolve Nintedanib well and used in the oil phase. HSP provides a systematic way to predict solvent compatibility, making it a valuable tool for addressing insolubility challenges in poorly soluble drugs. By ensuring compatibility between Nintedanib and the chosen excipients, HSP helped optimize drug loading within the formulation, ultimately contributing to improved bioavailability. HSP enhances bioavailability by identifying excipients that not only dissolve the drug effectively but also facilitate its incorporation into a stable microemulsion, improving its dispersion and absorption in the gastrointestinal tract. The Eugenol: Benzyl Alcohol [1:2] blend created the largest microemulsion region, showing the best self-emulsification potential. Tween 20, chosen for its good surfactant properties, was tested at higher concentrations (50%), resulting in smaller droplet sizes (5 nm) and faster emulsification. The permeability study showed that SMEDDS significantly improved Nintedanib’s ability to cross Caco-2 cell layers, with the Eugenol: Benzyl Alcohol [1:3] mix reaching a high permeability level (Papp = 1.08 × 1 0⁻⁶ cm·s⁻¹). Efflux ratio tests also suggested that Nintedanib is less likely to be affected by P-glycoprotein, which is important for improving absorption. However, there were some limitations, like the lack of stability testing, the potential for phase separation, and the need to confirm these findings in animal models. Despite these, the results show SMEDDS could be a promising strategy to boost Nintedanib’s bioavailability, and further testing is needed.