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Electrodynamic Investigations of Ion Transport and Structural Properties in Drug-Containing Gels: Dielectric Spectroscopy and Transient Current Measurements on Catanionic Carbopol Systems
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
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 Science and Technology, Technology, Department of Engineering Sciences.ORCID iD: 0000-0002-5496-9664
2005 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 109, no 32, 15250-15255 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study is to show the potential of using electrodynamic methods as characterization tools in the controlled drug release process, on complex drug release systems. The two formulations under study were a Carbopol gel containing diphenhydramine and an identical gel also containing the surfactant sodium dodecyl sulfate which forms catanionic vesicles with the diphenhydramine. The average diffusion coefficients were calculated from both the dielectric spectroscopy and the transient current measurements. Comparing the herein-obtained diffusion coefficients with those obtained in another study using a traditional USP technique for the same system, the values are virtually the same. The two electrodynamic methods proved to be potentially valuable tools for obtaining information about the concentration and the motion of the drug molecules inside the gel. The transient current measurements are particularly interesting in this case, as the method gives information not only on an average level, but also of the different charged moieties separately. Interestingly, it seems that the methods also are applicable for obtaining information about the mesh size in the gel.

Place, publisher, year, edition, pages
2005. Vol. 109, no 32, 15250-15255 p.
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:uu:diva-96416DOI: 10.1021/jp0511350OAI: oai:DiVA.org:uu-96416DiVA: diva2:170983
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. Drug Diffusion and Nano Excipient Formation Studied by Electrodynamic Methods
Open this publication in new window or tab >>Drug Diffusion and Nano Excipient Formation Studied by Electrodynamic Methods
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

New smart drugs demand new smart drug delivery systems and also new smart analysis methods for the drug delivery process and material characterization. This thesis contributes to the field by introducing a new electrodynamic approach for studying the drug diffusion proc-esses as well as the formation of a new type of drug delivery systems, the so called mesoporous nano excipients.

Drug diffusion processes from different pharmaceutical materials were examined. The transport of charged drug substances was investigated by electrodynamic methods; either as a release process governed by diffusion using the alternating ionic current method or by applying a voltage, sinusoidal or dc, to force the drug ions to move in an electric field.

Temperature-dependent drug release from microcrystalline cellulose tablets was examined in order to extract information about the diffu-sion process. Percolation theory was also employed to binary mixtures of an insoluble and electrically insulating matrix material together with a soluble and ionic conducting drug. Further, dielectric spectros-copy was proven to be a powerful method for examining the state of vesicle formation of drug and surfactant molecules in a carbopol gel. Finally, a new potential class of pharmaceutical materials were exam-ined, namely the AMS-n mesoporous materials, showing that the al-ternating ionic current method is powerful both in the study of the synthesis of and in the release process from these.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 73 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 293
Keyword
Functional materials, drug release, electrodynamic methods, diffusion, Funktionella material
Identifiers
urn:nbn:se:uu:diva-7818 (URN)978-91-554-6864-4 (ISBN)
Public defence
2007-05-07, 2001, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00
Opponent
Supervisors
Available from: 2007-04-13 Created: 2007-04-13 Last updated: 2015-09-11Bibliographically approved

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Bramer, TobiasStrömme, Maria

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