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Implications of regular solution theory on the release mechanism of catanionic mixtures 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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2009 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 71, no 2, 214-225 p.Article in journal (Refereed) Published
Description
Abstract [en]

The aim of this study was to apply the regular solution theory of mixed  micelles to gain new insights on the drug release mechanism, when using   catanionic mixtures as a method of obtaining prolonged release from   gels. Synergistic effects were investigated at equilibrium and   quantified in terms of regular solution theory interaction parameters.  The drug release from catanionic aggregates was studied both in a polymer free environment, using dialysis membranes, and in gels, using  a modified LISP paddle method. The drug release kinetics was modelled   theoretically by combining the regular solution theory with Fick's   diffusion laws assuming a contribution to the transport only from monomeric species (stationary aggregates). The theoretical predictions were found to be in reasonably good agreement with experiments. An analysis of the calculated distribution of species between aggregated and monomeric states was shown to provide further insights into the release mechanism.

Place, publisher, year, edition, pages
2009. Vol. 71, no 2, 214-225 p.
Keyword [en]
Vesicle, Micelle, Catanionic, Regular solution theory, Diffusion
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96417DOI: 10.1016/j.colsurfb.2009.02.008ISI: 000266897900008PubMedID: 19286357OAI: oai:DiVA.org:uu-96417DiVA: diva2:170984
Available from: 2007-11-16 Created: 2007-11-16 Last updated: 2017-12-14Bibliographically 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. Molecular Arrangement, Electronic Structure and Transport Properties in Surfactant Gel- and Related Systems Studied by Soft X-ray and Dielectric Spectroscopy
Open this publication in new window or tab >>Molecular Arrangement, Electronic Structure and Transport Properties in Surfactant Gel- and Related Systems Studied by Soft X-ray and Dielectric Spectroscopy
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis concerns studies of aqueous soft matter systems, especially surfactant micelle systems.

The aim has been to study the molecular arrangement and electronic structure of the constituents of, as well as transport properties in such a system. The molecular arrangement and electronic structure has been studied by means of X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray spectroscopy (RIXS). The transport properties have been investigated by low-frequency dielectric spectroscopy (LFDS) and small angle X-ray scattering (SAXS) as well as a theoretical modelling. The latter was based on Fick’s laws of the release from binary surfactant system and was validated by experiments.

The RIXS and XAS measurements show the electronic structure in bulk water and the influence of the chemical surrounding of the water molecule in bulk water and of the water molecules confined in a micelle lattice. The spectra are highly dependent on the molecular arrangement in such systems. For glycine and sodium polyacrylate RIXS and XAS spectra show features which are unique for carboxyl and carboxylate groups and such measurements can thus be used for fingerprinting.

The LFDS and SAXS measurements show a strong correlation between structure in a surfactant/poly-ion system and apparent mobility of surfactants. This conclusion is in line with earlier observations.

By the theoretical modelling a predictive model for the surfactant release from a binary surfactant micelle system has been obtained and the importance of different factors for surfactant release has been further clarified.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 77 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1060
Keyword
surfactants, surfactant/poly-ion gel, water, confined water, XAS, RIXS, dielectric spectroscopy, SAXS, pKa, transport, Fick’s law
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-205072 (URN)978-91-554-8721-8 (ISBN)
Public defence
2013-09-27, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:30 (Swedish)
Opponent
Supervisors
Available from: 2013-09-04 Created: 2013-08-13 Last updated: 2014-01-08

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