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

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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.

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Acknowledgements

We thank Chunhua Hu, PhD, at the Department of Chemistry of New York University for his assistance in acquiring XPRD data and the support by the National Science Foundation under award numbers CRIF/CHE-0840277 and by the NSF MRSEC Program under award number DMR-0820341.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, St. John’s University, 8000 Utopia Pkwy, Queens, NY, 11439, USA

    Meiki Yu, Louis Trombetta & Parnali Chatterjee

  2. Department of Chemistry, St. John’s University, 8000 Utopia Parkway, Queens, New York, 11439, USA

    Joseph E. Ocando

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  1. Meiki Yu
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  2. Joseph E. Ocando
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Correspondence to Parnali Chatterjee.

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Yu, M., Ocando, J.E., Trombetta, L. et al. Molecular Interaction Studies of Amorphous Solid Dispersions of the Antimelanoma Agent Betulinic Acid. AAPS PharmSciTech 16, 384–397 (2015). https://doi.org/10.1208/s12249-014-0220-x

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