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Rheological studies of the gelation of deacetylated gellan gum (Gelrite®) in physiological conditions
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.
1999 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 9, no 1, 99-105 p.Article in journal (Refereed) Published
Description
Abstract [en]

Gels have been successfully used to increase the mucosal contact time and hence the bioavailability of nasal and ophthalmic formulations. The use of in situ gelling polymers requires a rapid sol-gel transition that produces a strong gel for an optimal contact time. In this study, the rheological behaviour of deacetylated gellan gum (Gelrite) was analysed in order to better understand the reasons for the good performance in humans. Thermal scans were used to study gel formation and other changes in the structure of the samples when the macromolecular and ionic contents were altered. The effect the different ions in tear fluid (Na+, K+, Ca2+) had on the gel strength and the consequences of dilution due to the ocular protective mechanisms were examined. Na+ was found to be the most important gel-promoting ion in vivo. It was also found that gels are formed in tear fluid even when the concentration of Gelrite) is only 0.1%. Samples with concentrations of Gelrite of 0.5-1% do not require more ions than 10-25% of those in tear fluid to form gels. These two findings can partly explain the good performance of Gelrite in vivo. Gels with a high elastic modulus can thus be formed even though dilution of instilled drops takes place.

Place, publisher, year, edition, pages
1999. Vol. 9, no 1, 99-105 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-90715DOI: 10.1016/S0928-0987(99)00051-2PubMedID: 10494003OAI: oai:DiVA.org:uu-90715DiVA: diva2:163169
Available from: 2003-09-02 Created: 2003-09-02 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Polymer Gels as Pharmaceutical Dosage Forms: Rheological Performance and Physicochemical Interactions at the Gel-Mucus Interface for Formulations Intended for Mucosal Drug Delivery
Open this publication in new window or tab >>Polymer Gels as Pharmaceutical Dosage Forms: Rheological Performance and Physicochemical Interactions at the Gel-Mucus Interface for Formulations Intended for Mucosal Drug Delivery
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Drug delivery to the nasal and ocular mucosa faces several obstacles. One of these is from the effective clearance mechanisms present in the nose and eye. Polymer gels with suitable rheological properties can facilitate the absorption of poorly absorbed drugs by increasing the contact time of the drug with the mucosa. This has been attributed to the rheological and mucoadhesive properties of the gel. The main objective of this thesis was to investigate the importance of these features for the anticipated in vivo contact time, here exemplified by the ocular and nasal routes of administration.

The in situ gelling polymer gellan gum was found to have a favourable rheological and in vivo performance. When administered in the nasal cavity of rats, a gel was formed that could remain at the site of administration for up to 4 hours. In addition, the epithelial uptake and transfer of a 3 kDa fluorescein dextran was higher than for a mannitol solution. Therefore, it was concluded that a gellan gum formulation should be a promising strategy for nasal drug delivery.

The potential mucoadhesive properties of a variety of polymer gels were investigated using a rheological method and by measuring the tensile force required to detach the gel from a mucosa. With both methods the rheological properties of the gel were a determining factor for the results obtained. The rheological method was found to have several limitations. One of these was that a positive response, interpreted as mucoadhesion, was only seen with weak gels. The tensile method could, in contrast, detect strengthening of the mucus only for strong gels. However, this method reflects the in vivo performance of the gel better than the rheological method.

Finally, dielectric spectroscopy was explored as a tool for investigating the likelihood of intimate surface contact between the gel and the mucus layer. This novel approach involved determining the ease with which a charged particle can pass the gel-mucus interface layer, and may enable the study of the events at the interface closer to the molecular level, than is possible with the rheological and tensile strength methods.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 76 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 293
Keyword
Pharmaceutics, gel, rheology, mucoadhesion, mucosal drug delivery, in situ gel, gellan gum, Carbopol, tensile strength, nasal mucosa, intranasal administration, dielectric spectroscopy, Galenisk farmaci
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-3538 (URN)91-554-5705-3 (ISBN)
Public defence
2003-09-26, B21, Uppsala Biomedicinska Centrum, Uppsala, 10:15
Opponent
Supervisors
Available from: 2003-09-02 Created: 2003-09-02Bibliographically approved
2. Controlled Release Gel Formulations for Mucosal Drug Delivery
Open this publication in new window or tab >>Controlled Release Gel Formulations for Mucosal Drug Delivery
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Drug delivery to nasal or ocular mucosa for either local or systemic action faces many obstacles – these routes are protected by effective mechanisms. Gel formulations with suitable rheological and mucoadhesive properties increase the contact time at the site of absorption. However, drug release from the gel must be sustained if benefits are to be gained from the prolonged contact time.

The work presented here is the characterization of gels and the determination of the mucoadhesive properties of polymers using rheology. Gelrite gels were formed in simulated tear fluid at concentrations of polymer as low as 0.1%, and it was shown that sodium was the most important gel-promoting ion in vivo. Rheology, although it may be a questionable technique for evaluating mucoadhesive properties of polymers, showed that interactions between mucin and polymers were most likely to be seen with weak gels.

It was possible to control the release of uncharged drug substances by including surfactants that form micelles in the gel. This release depended on lipophilic interactions between the drug and the polymer and/or the micelles. Controlled-release formulations of charged drugs could be designed by mixing the drugs with oppositely charged surfactants in certain ratios. In this way, vesicles in which the drug and surfactant constituted the bilayer formed spontaneously. The vesicle formation was affected by the presence of polymer, and very small vesicles that gave a slow release rate were formed when a lipophilically modified polymer was used.

The gels were also evaluated in the Ussing chamber using porcine nasal mucosa. The rate of transport of drugs through the mucosa could be controlled by the rate of release from the formulation. Furthermore, the Ussing chamber could be used to evaluate the potential toxicity of formulations.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2001. 52 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 259
Keyword
Pharmacy, FARMACI
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutics
Identifiers
urn:nbn:se:uu:diva-1493 (URN)91-554-5173-X (ISBN)
Public defence
2001-12-07, B42, BMC, Uppsala, 09:15
Opponent
Available from: 2001-11-15 Created: 2001-11-15 Last updated: 2013-06-12Bibliographically approved

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