摘要：

This study describes the design, formulation and characterisation of a moisture-activated device incorporating the tetracaine phase-change system for percutaneous local anaesthesia. Gel intermediates for candidate devices were formulated with various concentrations of bioadhesive polymer, viscosity builder and tetracaine at pH values from 5 to 10. Gels were cast onto a release liner, dried and a backing layer attached, thus forming a percutaneous anaesthetic patch system. Patches were characterised by in vitro measurement of tetracaine flux through a polydimethylsiloxane barrier membrane, apparent viscosities of the casting gels, patch bioadhesion to a porcine skin substrate, uniformity of drug content and chemical stability of the active agent in the system. The clinical efficacy of candidate formulations was evaluated by a volunteer trial. Patches were of a consistent appearance and exhibited a uniform thickness and drug distribution throughout the matrix. Varying formulation parameters significantly ( p <0.05) affected drug release, patch viscosity and, thus, clinical efficacy. Tetracaine was stable in the patch system during storage for 6 months at 4 and 25°C. Patches with lower concentrations of bioadhesive and thickener, formulated at pH 8 or above, demonstrated the highest levels of drug flux and provided optimum percutaneous anaesthetic activity. All volunteers reported complete cutaneous anaesthesia at the treated site, with a mean onset time for anaesthesia of 44+6.7 min. The optimised bioadhesive patch device offered a more patient-compliant and convenient alternative to tetracaine percutaneous anaesthetic gel, particularly where large areas of skin are to be treated.

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