Microwave coprocessing of modafinil with Gelucire®: Thermal and compression characteristics

Abstract

Introduction: Modafinil, a wakefulness-promoting agent, is primarily used to treat excessive daytime sleepiness associated with narcolepsy and fatigue. As a BCS class II drug, modafinil exhibits low solubility and high permeability, with its crystalline structure significantly impacting dissolution, bioavailability, and compressibility. This study explores the use of microwave energy to alter the crystalline structure of modafinil in the presence of Gelucire® 48/16, aiming to improve its pharmaceutical properties. Methods: Modafinil was treated with microwave energy to form complexes with Gelucire® 48/16, and the resulting formulations were compared to hot-melt complexes and physical mixtures. The structural and thermal properties of the complexes were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Compressibility and compactibility were evaluated through Kawakita model analysis and response surface methodolog). The effect of microwaves on molecular interactions was further investigated using molecular modeling. Results: XRPD analysis revealed distinct crystalline patterns for microwave and hot-melt complexes compared to physical mixtures, with increased amorphousness observed through crystallinity, relative crystallinity, and relative intensity parameters. DSC thermograms indicated a reduction in melting endotherms and heat flow, suggesting structural changes due to complex formation. Compressibility and compactibility studies demonstrated optimal performance at low Gelucire® content, with microwave-treated complexes exhibiting superior properties to untreated mixtures. Molecular modeling confirmed dipole-dipole interactions between modafinil and the hydrophilic portion of Gelucire®. Conclusions: The study demonstrates that microwave energy effectively alters the crystalline structure of modafinil in the presence of Gelucire® 48/16, enhancing its amorphousness, compressibility, and compactibility. These findings highlight the potential of microwave-assisted complexation as a novel approach to improve the pharmaceutical performance of BCS Class II drugs like modafinil.

Keywords

• Tablet compressibility
• crystallinity
• molecular modeling
• carbonyl oxygen of modafinil