Evaluation of local anesthesia provided by transdermal patches containing different formulations of tetracaine.

Topical formulations of tetracaine in vehicles of propylene glycol and saline are tested on human volunteers with standard occlusive, adhesive, transdermal patches. The effects of formulation composition, dose, and onset time are investigated. Dose-response studies indicate that the optimum formulation for the diffusion of tetracaine in vivo is 60% free base and 40% acid salt (w/w) in 40% propylene glycol and 60% saline (v/v). A concentration of 0.3 M [8.3% (w/v)] tetracaine is sufficient to reach the dose plateau. Time-response studies indicate that high concentrations of tetracaine in the optimum formulation [1.1 and 1.8 M, 30 and 50% (w/v), respectively] can produce statistically significant analgesia relative to a placebo after 45 min. Comparison of these in vivo data with earlier in vitro data indicate that the optimum formulation with regard to clinical studies is identical to that for in vitro diffusion through hairless mouse skin [60% free base and 40% acid salt (w/w) in 40% propylene glycol and 60% saline].

Controlled release of steroids through microporous membranes with sodium dodecyl sulfate micelles.

The effect of solubilization by sodium dodecyl sulfate (SDS) micelles on the transport of steroids across synthetic microporous membranes has been studied experimentally in a diffusion cell and compared with theoretical calculations. The model used for calculations accounted for the fluxes of free and micelle-solubilized drug. Since the pores of the microporous membranes were only 10 times larger than the micelle, hindered diffusion effects for the micelles were taken into account. The compounds of interest (hydrocortisone, testosterone, and progesterone) had a wide range of aqueous solubilities and distribution coefficients between the aqueous and the micellar phases. In general, the theoretical predictions of drug diffusion agreed with the data to within approximately 10%.

Transport of micelle-solubilized steroids across microporous membranes.

The effect of solubilization by micelles on the transport of steroids across microporous membranes has been studied theoretically and experimentally. Our theoretical model requires the following parameters: micelle and drug diffusion coefficients in free solution, the distribution coefficient of the drug between the bulk and micellar phases, and micelle and membrane pore radii. The steroids used were hydrocortisone, testosterone, and progesterone. Since the model accounts for the flux of free drug as well as micelle-solubilized drug, the distribution coefficient of the drug between micelles and the aqueous phase had to be determined by solubilization experiments for each of the steroids. Membrane pore diameters, as determined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), ranged from approximately 500 to 4000 A. Steroid diffusion coefficients were calculated from membrane diffusion experiments. Quasi-elastic light scattering was used to find the free-solution diffusion coefficients and hydrodynamic radii of the micelles. With these experimentally determined parameters, the model is shown to be capable of predicting the rate of transport of micelle-solubilized drugs through microporous membranes. The application of our model to the design of controlled-release devices is also discussed.