Molecular Interaction Studies of Amorphous Solid Dispersions of the Antimelanoma Agent Betulinic Acid

Betulinic acid (BA), a novel natural product with antimelanoma activity, has poor aqueous solubility (< 0.1 mu g/mL) and therefore exhibits poor bioavailability. The purpose of this study was to explore the feasibility of preparing BA solid dispersions (BA-SDs) with hydrophilic polymers to enhance the aqueous solubility of BA. Melt-quenched solid dispersions (MQ-SDs) of BA were prepared at various ratios with the hydrophilic polymers including Soluplus, HPMCAS-HF, Kollidon VA64, Kollidon K90, and Eudragit RLPO. BA was found to be miscible in all polymers at a 1:4 (w/w) ratio by modulated differential scanning calorimetry (MDSC). BA/Soluplus MQ-SD exhibited the highest solubility in simulated body fluids followed by BA/Kollidon VA64 MQ-SD. The MQ-SDs of BA/Soluplus, BA/HPMCAS-HF, and BA/Kollidon VA64 were found to be amorphous as indicated by X-ray powder diffraction (XRPD) studies. Fourier transform infra-red (FT-IR) studies indicated molecular interactions between BA and Soluplus. Our preliminary screening of polymers indicates that Soluplus and Kollidon VA64 exhibit the greatest potential to form BA-SDs.