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Catanionic mixtures involving a drug: A rather general concept that can be utilized for prolonged drug release from gels
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
2006 In: Journal of Pharmaceutical Sciences, ISSN 00223549, Vol. 95, no 4, 769-780 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2006. Vol. 95, no 4, 769-780 p.
Identifiers
URN: urn:nbn:se:uu:diva-96413OAI: oai:DiVA.org:uu-96413DiVA: diva2:170980
Available from: 2007-11-16 Created: 2007-11-16 Last updated: 2011-05-04Bibliographically approved
In thesis
1. Prolonged Drug Release from Gels, using Catanionic Mixtures
Open this publication in new window or tab >>Prolonged Drug Release from Gels, using Catanionic Mixtures
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The use of catanionic drug-surfactant mixtures was proven to be an efficient novel method of obtaining prolonged drug release from gels. It was shown that various commonly used drug compounds are able to form catanionic mixtures together with oppositely charged surfactants. These mixtures exhibited interesting phase behaviour, where, among other structures, vesicles and large worm-like or branched micelles were found. The size of these aggregates makes them a potential means of prolonging the drug release from gels, as only monomer drugs in equilibrium with larger aggregates were readily able to diffuse through the gel. When the diffusion coefficient for drug release from the formulation based upon a catanionic mixture was compared to that obtained for the drug substance and gel alone, the coefficient was some 10 to 100 times smaller.

The effects of changes in the pH and ionic strength on the catanionic aggregates was also investigated, and this method of prolonging the release was found to be quite resilient to variations in both. Although the phase behaviour was somewhat affected, large micelles and vesicles were still readily found. The drug release was significantly prolonged even under physiological conditions, that is, at a pH of 7.4 and an osmolality corresponding to 0.9% NaCl.

Surfactants of low irritancy, capric and lauric acid, may successfully be used instead of the more traditional surfactants, such as sodium lauryl sulfate (SDS), and prolonged release can still be obtained with ease.

Some attempts to deduce the release mechanism from the proposed systems have also been made using transient current measurements, dielectric spectroscopy, and modelling of the release using the regular solution theory. In these studies, the previous assumptions made concerning the mechanism responsible for the release were confirmed to a large extent. Only small amounts of the drug existed in monomer form, and most seemed to form large catanionic aggregates with the oppositely charged surfactant.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 65
Keyword
Pharmaceutics, gel, catanionic, vesicle, micelle, controlled release, diffusion, surfactant, drug delivery, Galenisk farmaci
Identifiers
urn:nbn:se:uu:diva-8303 (URN)978-91-554-7017-3 (ISBN)
Public defence
2007-12-07, B42, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2007-11-16 Created: 2007-11-16Bibliographically approved
2. 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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