Dynamic in-situ eutectic formation for topical drug delivery

Objectives: The relationship between the solution-state chemistry of eutectic systems and their transmembrane transport characteristics is difficult to define as these mixtures are sensitive to delivery vehicle-induced penetration enhancement. Through in-situ formation of a molten eutectic mixture using highly evaporative sprays this study aimed to gain an understanding of solution-state thermodynamic and chemical properties of eutectic combinations pertinent to transmembrane transport in the absence of a delivery vehicle.

Methods: In-situ molten lidocaine-prilocaine eutectics were formed using a hydroflouroalkane (HFA) propellant. Transport through silicone membranes and human skin in upright Franz diffusion cells was determined using in-house manufactured creams as controls.

Key findings: The application of the two drugs in an HFA spray produced a molten oil even when the melting point of the drug mixture was above the experimental temperature at the membrane surface. In the absence of vehicle effects, molecule presentation to the membrane interface was most effective using a lidocaine-rich mixture of 0.7% w/w lidocaine: prilocaine -1985.06 +/- 128.87 mu g/h/cm(2).

Conclusions: There appeared to be no link between melting point and transmembrane transport of lidocaine: prilocaine from a eutectic mixture. The rate of drug presentation to the membrane interface, which was highest in drug-rich, high-activity molten eutectic mixtures, was the driver for transmembrane transport in the absence of significant barrier interactions.