Drug Release Studies on an Oil–Water Emulsion Based on a Eutectic Mixture of Lidocaine and Prilocaine as the Dispersed Phase

• Published in: Journal of pharmaceutical sciences 1986-04, Vol.75 (4), p.365-373
• Main Authors: Nyqvist-Mayer, Adela A., Brodin, Arne F., Frank, Sylvan G.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Delayed-Action Preparations; Diffusion; Emulsions; General pharmacology; Hydrogen-Ion Concentration; Lidocaine - analysis; Medical sciences; Membranes, Artificial; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Prilocaine - analysis; Solubility; Surface-Active Agents; Viscosity
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600750409

The in vitro drug release properties of a topical anesthetic formulation known to be effective on intact skin, based on a 1:1 eutectic mixture of lidocaine and prilocaine emulsified in water, were investigated with a poly(dimethylsiloxane) membrane partition model. Aqueous solutions and solubilized systems of lidocaine and prilocaine in a 1:1 ratio by weight were also included in the study as well as the eutectic mixture itself. Two identical sets of samples were used, one of which was gelled with carbomer 934 P. Drug solubilities in the membrane, partition coefficients between membrane and water, and diffusion coefficients in the membrane and the formulations were determined. As in the case of an aqueous medium, lidocaine and prilocaine in combination had lower solubilities in the membrane than they did separately. However, in the aqueous phase or in the membrane, the diffusion coefficients were mutually independent. Carbomer 934P, when neutralized totally with sodium hydroxide, did not decrease the aqueous diffusivities of the local anesthetic bases. The major advantages of using the emulsion formulation based on a eutectic mixture rather than more conventional formulations are: (a) the local anesthetic bases are present in their permeable uncharged forms; (b) the use of a poor solvent, water, as the vehicle provides a saturated system at low concentrations; (c) lipophilic solvent is absent in the dispersed phase, the presence of which would decrease the effective distribution coefficients of the active substances between the skin and the formulation; (d) the droplets consist of dissolvable drug and act as reservoirs to obtain steady-state release; and (e) the fluid state of the excess drug provides a higher dissolution rate than from a solid state.