Development Of Oral Liquisolid Systems For The Poorly Water-Soluble Drug Eluxadoline Using The Mixed Solvency Concept

Abstract

The present study aimed to enhance the solubility and dissolution rate of the poorly water-soluble drug Eluxadoline through the development of an oral liquisolid system using the mixed solvency concept. Calibration curves of Eluxadoline in distilled water and 0.1 N HCl showed linearity at 241 nm over the concentration range of 20–100 µg/ml. Solubility enhancement was achieved using a mixed solvent system of propylene glycol (PG) and polyethylene glycol 400 (PEG 400) (1:1) incorporating solid solubilizers such as sodium caprylate, sodium benzoate, and PVP K25. Among various blends, Blend A (5% SC + 2.5% SB + 2% PVP K25 + 0.5 ml PG + 0.5 ml PEG 400) exhibited the highest equilibrium solubility of 142.012 mg/ml. Compatibility and interference studies confirmed no interaction between the drug and excipients. Microcrystalline cellulose (Avicel PH 200) was used as the carrier and Aerosil (5%) as the coating material. Three liquisolid formulations (LS-01, LS-02, LS-03) were prepared and evaluated. All showed uniform drug content (97.77–99.52%) and improved dissolution compared to pure drug. LS-01 exhibited the best performance, achieving 99.77% release within 45 minutes. The optimized formulation was successfully scaled up using 9.5 mL of Blend A, 1250 mg of Eluxadoline, and 19,375 mg of Avicel PH 200. The final batch demonstrated a drug content of 98.92%, with a disintegration time ranging from 57 seconds to 3 minutes 10 seconds. In comparison studies, LS-01 exhibited 95.42% drug release within 10 minutes, whereas the pure drug showed only 55.06% release after 60 minutes. These outcomes confirm a significant improvement in dissolution rate and suggest enhanced bioavailability of the optimized formulation.