title: The effect of rheological behaviour of a topical anaesthetic formulation on the release and permeation rates of the active compound.
abstract: The objective of this study was to investigate the possibility of developing a topical cream that allows maximum release rate of the active compound while having suitable consistency, i.e., sufficient apparent plasticity. A submicron (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 polyethylene glycol 4000 (PEG4000). Various concentrations of the polymers were used in order to produce different rheological behaviours. The amount of drug passing through the membrane was measured as a function of time, using static diffusion cells with either Silastic sheeting 500-1 or guinea pig skin as membrane. The emulsion without polymer was used as reference. Rheological measurements were performed, giving the viscosity and the apparent yield stress of the formulations. Furthermore, theoretical values for diffusion coefficients and diffusion pathways were estimated and compared with the experimental data to discuss different diffusion models. Gelling polymers have been shown to produce an increase in the macroviscosity, thus inhibiting the diffusion of the oil droplets in the formulation without affecting the molecular diffusion. However, we suggest that when a compound of limited solubility is emulsified, the intact oil droplets contribute to the transport of the compound through the formulation. Thus, both release and permeation rates are decreased as the apparent yield stress, i.e., the macroviscosity of the formulation, is increased sufficiently by addition of gelling polymers.
authors.affiliation: AstraZeneca, SE-151 85 Södertälje, Sweden. katayoun.welin-berger@astrazeneca.com
authors.forename: K
authors.initials: K
authors.lastname: Welin-Berger
authors.forename: J A
authors.initials: JA
authors.lastname: Neelissen
authors.forename: B
authors.initials: B
authors.lastname: Bergenståhl
mesh_terms: D000287:Administration, Topical; D000465:Algorithms; D000779:Anesthetics, Local / Q000737:chemistry*; D004655:Emulsions; D005079:Excipients; D008567:Membranes, Artificial; D008962:Models, Theoretical; D010539:Permeability; D011108:Polymers; D011437:Propylamines / Q000737:chemistry; D012212:Rheology; D013696:Temperature; D014783:Viscosity
chemical_list: D000779:Anesthetics, Local; D004655:Emulsions; D005079:Excipients; D008567:Membranes, Artificial; D011108:Polymers; D011437:Propylamines; C434673:isopropylmethyl-(2-(3-propoxyphenyl)ethyl)amine