Designing and in vivo evaluation of microemulsion formulation containing capsaicin for the treatment of neuropathic pain

Capsaicin (CAP) is the compound found in chili peppers and responsible for their bitter taste, burning, and irritant effect. It has been used for the treatment of pain disorders, especially in neuropathic pain (NP). CAP is more effective at higher doses however, its side effects increase with higher doses. In this study, novel oral microemulsion capsaicin formulation (ME CAP) has been developed in order to increase the solubility, in vivo bioavailability and decrease adverse effects of CAP. The effect of ME CAP evaluated by comparing with commercially available oral CAP preparations on neuropathic mice. Micro emulsions are dispersions of water and oil. This form of oil-water mixtures is homogeneous, transparent, and thermodynamically stable. Stabilization of mixture is achieved by a surfactant, usually in combination with a co-surfactant. The micro-emulsion was prepared using oleic acid, Tween 80, propylene glycol, ethanol and water. Pseudo ternary phase diagrams were constructed to determine the area of the microemulsion at different ratios of surfactant to co-surfactant. The optimum formulation on different physicochemical characteristics such as globule size, pH, and stability were studied. The sciatic nerve partial tight ligation (PSL) model was used to induce NP in mice. Thermal and mechanical stimuli were used to evaluate allodynia, which is one of the most important signs of NP. After two weeks, NP was tested using the cold plate method and von Frey filaments testing. The mice in the treatment group were administered 10 mg/kg capsaicin by oral gavage. The effects of conventional (classic) capsaicin, which is frequently used in neuropathies, and ME CAP in this study were compared. Our results showed that the presented formulation is more effective than classic CAP with Von Frey test while showing no difference between them with the cold plate test. Therefore, the developed ME CAP formulation at lower doses could reduce side effects and improve the bioavailability of the orally administered CAP in the treatment of NP, and thus would get a good patient compliance.