Amorphous solid dispersions of hecogenin acetate using different polymers for enhancement of solubility and improvement of anti-hyperalgesic effect in neuropathic pain model in mice

作者：de Franca Almeida Moreira Carlos Democedes Luis; de Oliveira Pinheiro Jonas Gabriel; da Silva Junior Walter Ferreira; Barbosa Euzebio Guimaraes; Maciel Lavra Zenia Maria; Menezes Pereira Erick Willyame; Resende Marilia Matos; de Azevedo Eduardo Pereira; Quintans Junior Lucindo Jose; de Souza Araujo Adriano Antunes; Siqueira Quintans Jullyana de Souza; Neves de Lima Adley Antonini

来源：Biomedicine & Pharmacotherapy, 2018, 97: 870-879.

DOI：10.1016/j.biopha.2017.10.161

• Hecogenin acetate
• Amorphous solid dispersion
• Hydrophilic polymer
• Neuropathic pain
• Mechanical hyperalgesia
• Thermal hyperalgesia

Hecogenin acetate (HA) is an acetylated sapogenin that has shown potential antihyperalgesic activity, inhibiting descending pain and acting in opioid receptors. However, HA exhibits poor aqueous solubility, which may limit its application. This study aims to develop amorphous solid dispersions (ASD) using five hydrophilic polymers, to characterize them and to evaluate their antihyperalgesic activity. Physicochemical characterization was performed by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared (FTIR) spectroscopy. In order to evaluate the hyperalgesia of the ASD, sciatic nerve crush injury (NCI) was induced in mice followed by administration of the ASD, where three parameters were evaluated: mechanical and thermal hyperalgesia as well as grip strength. XRD and SEM showed that ASD of HA with HPMC obtained by kneading (KND) presented an amorphous profile, unlike the others polymers, indicating interaction between HA and HPMC. FTIR analysis evidenced the strong interaction between HA and HPMC. Although the results of mechanical hyperalgesia were slightly improved on the groups treated with ASD of HA with HPMC, the thermal hyperalgesia showed that the incorporation of HA into HPMC matrix significantly improved its antinociceptive activity.

• 出版日期2018-1