The effect of theological behaviour of a topical anaesthetic formulation on the release and permeation rates of the active compound

The objective of this study was to investigate the possibility of developin g a topical cream that allows maximum release rate of the active compound w hile having suitable consistency, i.e., sufficient apparent plasticity. A s ubmicron (o/w) emulsion containing a model compound was investigated in the presence and absence of different polymers: sodium carboxymethylcellulose (CMC), Carbopol 934P (C934), polyethylene glycol 400 (PEG400) and polyethyl ene glycol 4000 (PEG4000). Various concentrations of the polymers were used in order to produce different theological behaviours. The amount of drug p assing through the membrane was measured as a function of time, using stati c diffusion cells with either Silastic((R)) sheeting 500-1 or guinea pig sk in as membrane. The emulsion without polymer was used as reference. Rheolog ical measurements were performed, giving the viscosity and the apparent yie ld stress of the formulations. Furthermore, theoretical values for diffusio n coefficients and diffusion pathways were estimated and compared with the experimental data to discuss different diffusion models. Gelling polymers h ave been shown to produce an increase in the macroviscosity, thus inhibitin g the diffusion of the oil droplets in the formulation without affecting th e molecular diffusion. However, we suggest that when a compound of limited solubility is emulsified, the intact oil droplets contribute to the transpo rt of the compound through the formulation. Thus, both release and permeati on rates are decreased as the apparent yield stress, i.e., the macroviscosi ty of the formulation, is increased sufficiently by addition of gelling pol ymers. (C) 2001 Elsevier Science BN. All rights reserved.