The formulation of a chloroquinoline derivative in an amorphous solid dispersion for improved solubility

Abstract

Poor aqueous solubility remains a major hurdle in the development of orally administered drugs, particularly those with promising pharmacological activity but limited bioavailability. This study addresses this issue through the formulation of an amorphous solid dispersion (ASD) containing a novel chloroquinoline derivative composed of chloroquinoline, urea, and benzothiazole moieties. The objective was to enhance the solubility and dissolution rate of this poorly soluble compound using polyvinylpyrrolidone (PVP K25) as a hydrophilic polymer carrier. The ASD was prepared via solvent evaporation, and a 1:4 drug-to-polymer ratio was identified as optimal based on preliminary miscibility and thermal analyses. Comprehensive physicochemical characterization was conducted using differential scanning calorimetry (DSC), modulated DSC (MDSC), X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), and polarised light microscopy (PLM). Thermal data confirmed the amorphous nature of the dispersion, with the disappearance of the crystalline drug melting peak and a single glass transition temperature (Tg), indicative of miscibility. XRPD and PLM further supported the loss of crystallinity in the ASD formulation. Solubility studies demonstrated a significant increase in aqueous solubility for the ASD compared to the raw material, and UV-Vis validated dissolution tests showed faster and more complete drug release in both water and acidic media. These findings confirm that the ASD strategy substantially improves the dissolution properties of the chloroquinoline derivative, laying the groundwork for further preclinical development.