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The effect of rheological behaviour of a topical anaesthetic formulation on the release and permeation rates of the active compound
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2001 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 13, no 3, 309-318 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2001. Vol. 13, no 3, 309-318 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-89451DOI: 10.1016/S0928-0987(01)00118-XPubMedID: 11384854OAI: oai:DiVA.org:uu-89451DiVA: diva2:160896
Available from: 2001-10-03 Created: 2001-10-03 Last updated: 2013-05-17Bibliographically approved
In thesis
1. Formulations, Release and Skin Penetration of Topical Anesthetics
Open this publication in new window or tab >>Formulations, Release and Skin Penetration of Topical Anesthetics
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes certain critical aspects of the development of semisolid topical anesthetic formulations requiring a fast onset of action. Furthermore, local anesthetics were investigated regarding their phase interaction with membrane lipids.

A new long acting and topically effective local anesthetic/analgesic agent, isopropyl-methyl-[2-(3-propoxyphenoxy)-ethyl]-amine (amino diether, AD), was used as the model compound. The nonionized form of AD is liquid oil at room temperature with low water solubility. A submicron o/w emulsion with Newtonian flow property was prepared with AD as the disperse phase. The kinetic stability of this emulsion was increased to prevent Ostwald ripening by addition of small amounts of a hydrophobic excipient to the disperse phase. The emulsion allowed a high in vitro release and permeation rate of AD as well as a sufficient in vivo efficacy.

To achieve a plastic property, hydrophilic polymers were added to the o/w emulsion resulting in a significant reduction of the release and permeation rate of AD. In order to avoid the addition of these polymers, a semisolid w/o emulsion was evaluated with AD as the continuous phase. The inherent plastic property of this formulation allows sufficient skin adhesion. Furthermore, the release and permeation rate of AD from this formulation is comparable to that of the Newtonian submicron o/w emulsion. A close correlation between the in vitro permeation studies and the in vivo human plasma profiles was observed using the convolution/deconvolution


Furthermore, x-ray and calorimetric data indicated that local anesthetics are able to interact with skin lipids both by increasing the chain fluidity of the crystalline lipids and by probably producing phase inversions in the grain borders of the stratum corneum lipid multilayers. It was also shown that this lipid interaction was not directly correlated with the different levels of skin permeation and/or topical efficacy of the investigated compounds.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2001. 53 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 258
Pharmacy, FARMACI
National Category
Pharmaceutical Sciences
Research subject
urn:nbn:se:uu:diva-1395 (URN)91-554-5115-2 (ISBN)
Public defence
2001-10-05, BMC, B22, Uppsala, 13:15
Available from: 2001-10-03 Created: 2001-10-03Bibliographically approved

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