Formulation and Characterization of Amorphous Coumarin Solid Dispersions by Spray Drying For Improved Aqueous Solubility

Abstract

Coumarin, a natural heterocyclic compound, exhibits significant pharmacotherapeutic potential including antibiotic, fungicidal, anti-inflammatory, anticancer, and anti-HIV activities. However, its poor aqueous solubility (10 µg/mL) and lipophilic character (Log P = 1.28) severely limit its oral bioavailability and therapeutic efficacy. This study aimed to overcome this challenge by enhancing coumarin's solubility and dissolution rate through the formulation of solid dispersions using physical mixing and spray drying techniques. Polyvinylpyrrolidone K30 (PVP K30) and beta-cyclodextrin were employed as hydrophilic carriers. Pure coumarin was identified and characterized by melting point (700c), UV spectroscopy (lambda max=317nm), FTIR (characteristic peaks at 1715cm−1, 1625cm−1), DSC (endothermic peak at 73.03 and PXRD (crystalline nature). Drug-excipient compatibility studies via FTIR and DSC indicated no significant interactions. Physical mixtures (PMs) with drug-to-carrier ratios of 1:1, 1:2, and 1:3 were prepared and showed marginal improvements in saturation solubility (up to 178 µg/mL for PM6) and dissolution. In contrast, solid dispersions (SDs) prepared by spray drying demonstrated markedly superior results. All spray-dried batches exhibited significantly enhanced saturation solubility, with SD3 (coumarin: PVP K30, 1:3) reaching 246 µg/mL in distilled water and 0.17µg/mL in pH 6.8 phosphate buffer. Dissolution studies revealed a dramatic increase in release rates, with SD3 achieving 25% drug release within 5 minutes, significantly outperforming PMs (5-8% in 5 min) and pure coumarin (75% > 120 min). The amorphous state of coumarin in SDs was confirmed by the absence of its characteristic melting peak in DSC thermo grams. Flow properties for both PMs and SDs were found to be acceptable. Drug release kinetics of spray-dried dispersions best fitted the Korsmeyer-Peppas model, indicating a complex release mechanism involving diffusion and/or polymer relaxation. These findings strongly suggest that spray drying with hydrophilic carriers, particularly PVP K30, is an effective strategy for overcoming the solubility limitations of coumarin, thereby paving the way for improved oral bioavailability and wider therapeutic applications.