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Catanionic aggregates formed from drugs and lauric or capric acids enable prolonged release from gels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2008 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 323, no 2, 386-394 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to add to the range of charged surfactants that can be used to form catanionic aggregates with oppositely charged surface active drug substances, and to apply these aggregates to prolong drug release from gels. The surfactants used in this study, lauric and capric acids are of natural origin-unlike traditionally used, synthetic, surfactants. The mixtures of drug substances and oppositely charged surfactants were studied visually and with cryogenic transmission electron microscopy. Drug release from gels was studied with a modified USP paddle method. This study shows that lauric and capric acids are as, or even more, active in forming catanionic aggregates than traditionally used surfactants such as sodium dodecyl sulfate. It is shown that the length of the hydrophobic part of the surfactant plays an important role in the formation of pharmaceutically interesting catanionic aggregates. As seen in previous studies, using catanionic vesicles prolongs the drug release from gels and decreases the apparent diffusion coefficient by a factor of 10-50, compared to a gel containing only drug substance.

Place, publisher, year, edition, pages
2008. Vol. 323, no 2, 386-394 p.
Keyword [en]
catanionic, vesicles, drug substances, surfactants, prolonged release, gels
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-16541DOI: 10.1016/j.jcis.2008.04.008ISI: 000256743300027PubMedID: 18479696OAI: oai:DiVA.org:uu-16541DiVA: diva2:44312
Available from: 2008-05-28 Created: 2008-05-28 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Catanionic Aggregates in Gels: Prolonged Drug Release and Potential Implications for Topical Use
Open this publication in new window or tab >>Catanionic Aggregates in Gels: Prolonged Drug Release and Potential Implications for Topical Use
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gels are popular dosage forms.  This topical dosage form may be advantageous compared to oral or parenteral dosage forms. Favorable rheological or bioadhesive properties of gels might provide extended contact times at the site of administration compared to aqueous solutions. However, due to the high water content of gels, these are usually quickly emptied of the drug substance. One way of prolonging the drug release from gels is to contain the drug substance in catanionic aggregates in the gel. These aggregates are formed in solutions of oppositely charged surfactants and a drug can be used instead of one of the surfactants.

 

In this thesis catanionic aggregates composed of drug substances and oppositely charged surfactants were studied and the possibility to use these aggregates for the purpose of prolonged drug release was investigated. The formation of catanionic aggregates when using drugs was found to be a common occurrence in addition to which, the oppositely charged surfactant can be varied and surfactants of natural origin with a low toxicity were used. Most combinations tested rendered either vesicles or elongated micelles. When the catanionic aggregates were contained in gels the drug release was substantially prolonged. The apparent diffusion coefficients were lowered 10-100 times compared to the reference gels. When gels with catanionic vesicles with substantial prolonged drug release were applied to skin the penetration rate was lowered extensively. No morphological differences were observed between skin samples that had been exposed to formulations containing catanionic aggregates and skin samples exposed to saline solution, air or formulations containing only the drug. Both conventional, covalently linked pre-formed gels and physical gels, where the catanionic vesicles form the cross-links upon interaction with the polymer, can be used for these purposes. When the effect of drug release on aggregate structure was studied, it was shown that vesicles are present in both conventional and physical gels throughout the drug release process.

 

This thesis shows that catanionic aggregates contained in gels can present an advantageous formulation strategy to prolong the drug release, thereby improving the efficiency of gel formulations.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 140
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutics
Identifiers
urn:nbn:se:uu:diva-138447 (URN)978-91-554-8019-6 (ISBN)
Public defence
2011-04-15, B 42, BMC, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-03-25 Created: 2010-12-17 Last updated: 2011-05-04Bibliographically approved

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Dew, NoelBramer, Tobias

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