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Stability and solution concentration enhancement of resveratrol by solid dispersion in cellulose derivative matrices

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Abstract

Resveratrol is a highly biologically active phytoalexin, found in many plant materials that are common elements of the human diet, such as grapes, nuts, and red wine. The therapeutic or disease preventative potential of this natural polyphenolic antioxidant has been limited in part due to its poor aqueous solubility and low oral bioavailability. We hypothesized that solid dispersion of resveratrol (Res) in cellulose derivative matrices might afford amorphous dispersions, from which supersaturated Res solutions would be produced in the human gastrointestinal (GI) tract, resulting in higher Res bioavailability. We carried out structure–property studies employing cellulose esters with a range of physical characteristics but possessing features suitable for use in amorphous solid dispersions: carboxymethylcellulose acetate butyrate (CMCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and cellulose acetate adipate propionate (CAAdP). The cellulose derivative results were compared with those of a negative control, pure crystalline Res, and a positive control, Res/poly(vinylpyrrolidinone) (PVP). Solid dispersions were characterized by powder X-ray diffraction (XRPD), modulated differential scanning calorimetry (MDSC), nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FT-IR) of solid dispersions. HPMCAS and PVP solid dispersions afforded faster and more complete Res release at pH 6.8; however Res is also released from PVP matrices at pH 1.2. The carboxyl-containing cellulose derivatives release Res to only a small extent at pH 1.2. This combination of solution and solid phase stabilization against crystallization, and pH-triggered drug release makes these cellulose esters attractive candidates for Res bioavailability enhancement.

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Acknowledgments

We thank USDA (Grant number 09-35603-05068) for financial support and the Virginia Tech Institute for Critical Technologies and Applied Science (ICTAS) for their support of this project. We thank Eastman Chemical Company and Shin-Etsu Ltd. for their gracious donations of CMCAB and HPMCAS, respectively.

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Authors and Affiliations

  1. Department of Sustainable Biomaterials, Virginia Tech, Blacksburg, VA, 24061, USA

    Bin Li & Kevin J. Edgar

  2. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, 47907, USA

    Lindsay A. Wegiel & Lynne S. Taylor

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  1. Bin Li
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  2. Lindsay A. Wegiel
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  3. Lynne S. Taylor
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  4. Kevin J. Edgar
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Correspondence to Kevin J. Edgar.

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10570_2013_9889_MOESM1_ESM.doc

Standard curves of Res UV–Vis absorption versus concentration in ethanol and in pH 6.8 buffer are included (S1). XRPD patterns of Res/polymer 1/1 SDs (S2). Modulated DSC heating curve of Res/CMCAB 1/9 SD (S3) (DOC 333 kb)

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Li, B., Wegiel, L.A., Taylor, L.S. et al. Stability and solution concentration enhancement of resveratrol by solid dispersion in cellulose derivative matrices. Cellulose 20, 1249–1260 (2013). https://doi.org/10.1007/s10570-013-9889-3

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  • DOI: https://doi.org/10.1007/s10570-013-9889-3

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