Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined. The extrudates were then obtained by blending the lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical microscopy and PXRD were used to characterize the extrudates. In vitro microemulsion reconstitution and drug release were also studied. L-SMEDDS gave rise to microemulsions with low mean size, PdI and zeta potential (140.04 ± 7.22 nm, 0.219 ± 0.011 and -9.77 ± 0.86 mV). S-SMEDDS were successfully prepared by HME, and an HMPCAS matrix was able to avoid microemulsion reconstitution and retain drug release in pH 1.2 (12.97%-25.54%). Conversely, microemulsion reconstitution and drug release were gradual in pH 6.8 and complete for some formulations. Extrudates prepared at the lowest drug concentration and highest temperature and recirculation time promoted a complete and rapid drug release in pH 6.8 giving rise to small and uniform microemulsion droplets.

The findings suggested that FB is the best alternative for large-scale production of solid dosage forms containing CARV. Additionally, the results suggest that HPγCD could be considered as another option for CARV complexation because of its excellent performance in inclusion complex formation in the solid state.

Skin ulcers, wounds, or burns represent a burden for health care worldwide. Our aim was to explore the effects of mucoadhesive formulation with Curcuma longa L. extract mucoadhesive formulation containing curcumin (MFC) on skin healing in Wistar rats. Fifty-four rats were randomly allocated into 3 groups: control, vehicle, and MFC. A full-thickness circular wound was induced on the back of each animal. Two daily applications of the products were performed according to the experimental group. On days 3, 10, and 21, 6 animals in each group were euthanized. Clinical analysis was based on wound area. Histologic analysis was performed in hematoxylin and eosin-stained sections, with re-epithelization and inflammation being assessed by means of semiquantitative scores. To analyze the Akt/mTOR pathway, immunohistochemistry for phospho Akt (pAkt) and phospho ribosomal protein S6 were investigated. In addition, nuclear factor kappa-light-chain-enhancer of activated B cells immunolabeling was performed. Clinical analysis revealed wounds with a smaller area on days 3 and 10 in curcumin-treated animals. Histologically, MFC had a significant impact on inflammatory events on days 3 and 10 and promoted faster re-epithelization, which was evidenced on day 10. MFCtreated wounds exhibited pAkt upregulation on day 10 and both pAkt and phospho ribosomal protein S6 downregulation on day 21. Nuclear factor kappa-light-chain-enhancer of activated B cells expression varied through the evaluation periods; however, no significant difference was observed between groups. Collectively, our results indicate that MFC is efficient in accelerating cutaneous wound repair through modulation of the inflammatory process and stimulus of re-epithelization by an Akt/mTOR-dependent mechanism.

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Artur Christian Garcia da SILVA (b) Eliana Martins LIMA (c) Ellen Cristine Pineze ALONSO (d) Ricardo Neves MARRETO (d) Elismauro Francisco MENDONÇA (a) Marize Campos VALADARES (e)