Amorphous solid dispersions of hecogenin acetate using different polymers


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.



According to the FTIR analysis, HPMC was the only hydrophilic polymer that was able to chemically interact with HA after mixing them by KND method. In addition, the significant reduction of the intensity of crystalline reflections and alteration of HA’s morphology, as evidenced by XRD and SEM analysis, respectively, suggest that an ASD of HA and HPMC was obtained by KND method. Therefore, this system was chosen for the in vivo evaluation of hyperalgesia.

The results of this study showed that both HA alone and its ASD with HPMC can reduce the mechanical and thermal hyperalgesia in NCI-induced mice. ASD-HPMC seems to improve the analgesic activityof HA, at least in heat-induced pain on NP model (NCI-induced mice). Hence, ASD of HA seems to be a promising alternative for the devel- opment of a new therapeutic approach in the management of NP.


Graphs of various analysis on Amorphous solid dispersions of hecogenin acetate
Physiochemical characterization and Evaluation of termal and mechanical hyperalgesion of Amorphous solid dispersions of hecogenin acetate