Highly Concentrated Eutectic Creams of Capsaicin for Long-term Analgesia

This study aimed to employ eutectic technology to formulate a stable, organic solvent-free and high-concentration capsaicin cream. Herein, menthol was selected to form a eutectic with capsaicin from ten compounds. The eutectic mixtures (EMs) were characterized by polarized optical microscopy (POM), differential scanning calorimetry (DSC), Fourier Transform Infrared (FT-IR) spectroscopy, and X-ray diffraction (XRD). The stability of the EMs in the cream was prolonged for over 8 months due to the interactions among capsaicin, menthol, Span 40, and polyvinyl alcohol (PVA). The rheological properties were further enhanced by incorporating white petrolatum and anhydrous calcium hydrogen phosphate into the eutectic cream, which indicated improved physical stability and spreadability. Moreover, the retention of capsaicin in porcine skin was comparable between the eutectic cream group (4% w/w capsaicin) and the Qutenza® group (8% w/w capsaicin). Once applied the capsaicin eutectic cream (4% w/w) to chronic constriction injury (CCI) model in mice, mechanical and thermal pain were alleviated in a manner similar to Qutenza®. Overall, the capsaicin eutectic cream was successfully prepared by combining eutectic, with a specific mixture of surfactant and PVA. Also, the cream showed excellent permeability and storage stability for topical application, which provided a promising potential for the development of long-acting analgesic drugs.