title: Molecular interaction studies of amorphous solid dispersions of the antimelanoma agent betulinic acid.
abstract: Betulinic acid (BA), a novel natural product with antimelanoma activity, has poor aqueous solubility (<0.1 μg/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.
authors.affiliation: Department of Pharmaceutical Sciences, St. John's University, 8000 Utopia Pkwy, Queens, NY, 11439, USA.
authors.forename: Meiki
authors.initials: M
authors.lastname: Yu
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Ocando
authors.forename: Louis
authors.initials: L
authors.lastname: Trombetta
authors.forename: Parnali
authors.initials: P
authors.lastname: Chatterjee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D053978:Pentacyclic Triterpenes; D011108:Polymers / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012995:Solubility; D014315:Triterpenes / Q000737:chemistry*; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D053978:Pentacyclic Triterpenes; D011108:Polymers; D011208:Powders; D014315:Triterpenes; D000094062:Betulinic Acid