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Inhibition of Ostwald ripening in local anesthetic emulsions by using hydrophobic excipients in the disperse phase
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2000 (English)In: Internation Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 200, no 2, 249-260 p.Article in journal (Refereed) Published
Abstract [en]

The stability of submicron emulsions of different local anesthetic/analgesic substances was investigated in the presence and absence of different hydrophobic excipients (ripening inhibitors). Ostwald ripening was believed to be the underlying mechanism for the instability of these emulsions. In the absence of ripening inhibitors, the mean droplet size of the emulsions increased from 100 nm to about 4-5 microm within an hour of manufacture. The addition of a small amount of a second component of lower solubility to the disperse phase decreased the rate of Ostwald ripening, producing good stability of the emulsions. The efficiency of the ripening inhibitors was directly proportional to their solubility in the disperse phase, i.e. the water. The lower the solubility, the more effective the stabilization of the emulsions. The experimentally observed rates of increase in droplet size in the emulsions were closely correlated with those predicted according to the Liftshitz-Slezov-Wagner (LSW) theory.

Place, publisher, year, edition, pages
2000. Vol. 200, no 2, 249-260 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-89450DOI: 10.1016/S0378-5173(00)00395-1PubMedID: 10867255OAI: oai:DiVA.org:uu-89450DiVA: diva2:160895
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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