Development of Amorphous Solid Dispersion to Improve the Dissolution and Antiproliferative Activity of Brazilin

Brazilin (BRZ), a major bioactive constituent of Caesalpinia sappan, exhibits promising anticancer activity but suffers from extremely poor aqueous solubility, limiting its oral bioavailability and therapeutic efficacy. Drug solubility is a critical determinant of absorption and therapeutic efficacy, so strategies to enhance the solubility of BRZ are essential. Amorphous solid dispersions (ASDs) have been widely employed to enhance the solubility and dissolution behavior of poorly soluble compounds. This study aimed to develop and characterize ASDs of BRZ using polyvinylpyrrolidone (PVP) as a polymer carrier, to investigate molecular interactions through in silico docking, and to evaluate their physicochemical properties, dissolution behavior, physical stability, and antiproliferative activity.

ASDs of BRZ with PVP were prepared using the solvent evaporation method with drug-to-polymer weight ratios of 1:1, 1:3, and 1:5. The formulations were characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier-transform infrared (FT-IR) spectroscopy. Solubility, in vitro dissolution, and antiproliferative activity against DU145 prostate cancer cells were evaluated. Physical stability was evaluated over 30 days under dry (25 °C/0% RH) and humid (25 °C/90% RH) storage conditions using PXRD to detect any possible recrystallization.

PXRD and DSC analyses confirmed the complete amorphization of BRZ within the ASD matrix, as evidenced by the disappearance of crystalline diffraction peaks and characteristic melting endotherms. FT-IR spectroscopy, supported by in silico studies, revealed hydrogen bond formation between the hydroxyl group of BRZ and the carbonyl group of PVP. The BRZ:PVP (1:5) formulation achieved a 5.7-fold increase in solubility compared to crystalline BRZ. Dissolution testing showed a characteristic spring-and-parachute profile, with ASDs maintaining supersaturation for a prolonged period. Moreover, enhanced antiproliferative activity against DU145 cells was observed for BRZ ASDs, with the lowest IC_{5 0} value of 14.02 µg/mL at a 1:5 ratio, compared to 20.12 µg/mL for crystalline BRZ. Stability testing showed that all ASDs maintained their amorphous form under dry storage conditions for 30 days, whereas samples stored at 90% relative humidity exhibited recrystallization.

BRZ ASDs using PVP effectively improved solubility, dissolution profile, and antiproliferative activity. The formulations demonstrated good stability under dry storage conditions but were sensitive to high humidity. These findings suggest that ASDs represent a promising strategy for enhancing the therapeutic potential of poorly soluble natural anticancer compounds.