Carboxymethyl Tamarind Gum-Based Amorphous Solid Dispersion of Voriconazole: Formulation, Characterization, Dissolution and Pharmacokinetic Evaluation
Abstract
Background: Voriconazole (VRZ) is a triazole antifungal agent with limited aqueous solubility, making dissolution an important formulation consideration. Solid dispersion (SD) technology can improve wetting, dispersion and the apparent dissolution of poorly water-soluble drugs. The present study investigated carboxymethyl tamarind gum (CMTG), a chemically modified natural polysaccharide, as a hydrophilic carrier for VRZ. Methods: CMTG was prepared from tamarind gum and characterized. VRZ-loaded SDs were prepared by the kneading method at drug:carrier ratios of 1:1, 1:2 and 1:3 using both native tamarind gum (TG) and CMTG. The SDs were evaluated for drug content, saturation solubility, dissolution, FTIR, DSC, PXRD, SEM and EDS. Antifungal activity against Candida albicans and an oral pharmacokinetic study in Wistar rats were also performed. The optimized SD was incorporated into immediate-release tablets by direct compression. Results: CMTG showed improved aqueous solubility compared with native TG and exhibited characteristic FTIR bands associated with carboxymethyl groups at approximately 1745.58 and 1402 cm−1. The optimized VRZ:CMTG SD5 (1:2) increased VRZ saturation solubility from 0.016±0.001 to 1.19±0.06 mg/mL, corresponding to a 74.37-fold enhancement. Pure VRZ showed 39% dissolution, whereas SD5 achieved complete release within 120 min. The SD produced a 24±1.2 mm zone of inhibition against C. albicans compared with 18±1.5 mm for pure VRZ. In rats, the SD produced a higher Cmax (0.964±0.01 µg/mL) than pure VRZ suspension (0.456±0.05 µg/mL), and Tmax was reduced from approximately 3 to 2 h. Conclusion: CMTG functioned as an effective natural-polymer carrier for VRZ SD, improving apparent solubility, dissolution and selected pharmacokinetic parameters. The findings support further development of CMTG-based amorphous SDs for poorly water-soluble antifungal agents.