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Drug Delivery Using Oral Vehicles: Controlled Release in the GI-tract
Norwegian University of Science and Technology, Faculty of Natural Sciences and Technology, Department of Biotechnology.
2012 (English)MasteroppgaveStudent thesis
Abstract [en]

Oral delivery is considered a convenient route for administration of pharmaceuticals. Great effort has been made to optimize oral delivery vehicles to increase the bioavailability of the pharmaceutical, and enhance patient compliance to ease swallowing. Emulsion-based gelled matrices have shown promising features as delivery systems. They are soft chewable matrices that are easy to swallow, and have the ability to entrap the pharmaceutical, providing prolonged, and controlled release to avoid fast dissolution in the stomach. The purpose of this study was divided into two main objectives. The first aim was to study emulsion-based gelatin matrices intended for oral drug delivery by investigation of the influence of gelatin type and/or oil content on the matrix properties. The second aim was to investigate the properties of multiple emulsions, regarding their potential as oral drug delivery systems for water-soluble pharmaceuticals, and controlled drug delivery. Emulsion-based matrices stabilized by 160g Bloom gelatins, either type A or B, and containing various amounts of corn oil (0, 10, 30 and 50 wt %) were subjected to rheological characterization and in vitro dissolution studies at simulated gastric conditions. The results showed an increase in viscosity, storage modulus and gelling and melting temperatures in line with increased oil content in the matrix, and to a larger extend for matrices with type A gelatin compared to type B. Longitudinal deformations of the gelled matrices did show a trend of slightly increasing Young’s modulus when oil was added to the matrix, but no clear trend was observed for force and strain at break. A correlation between rheological matrix properties and dissolution time was observed: An increase in dissolution time with higher fractions of oil and prolonged dissolution time for matrices with type A gelatin compared to type B. Overall the results showed that different oil contents and gelatin types changed the physical properties of the matrices, providing a possibility to tailor matrices to obtain suitable delivery systems for various pharmaceuticals. Water-in-oil-in-water double emulsions, stabilized by either 226g Bloom gelatin type B or tween80 was examined by long time stability studies, and by in vitro lipolysis studies simulating small intestinal conditions. The water-soluble marker tartrazine, was entrapped in the inner water phase of the emulsions. The release of tartrazine was measured during a period of 78 days and both double emulsions with gelatin and tween80 were found to possess long-term stability at room temperature. In vitro lipolysis of gastric stable double emulsions stabilized by gelatin was conducted in a dissolution medium containing bile extracts, with or without lipases. A complete release of tartrazine was obtained; both in the presence and absence of lipases, while a faster release was observed when lipases were present. Although the release mechanism was not completely determined, the results indicate that release of drugs can occur in the small intestines due to lipolysis. The double emulsions thus offer great potential in delivery of gastric unstable pharmaceuticals.

Place, publisher, year, edition, pages
Institutt for bioteknologi , 2012. , 132 p.
Keyword [no]
ntnudaim:6724, MBIOT5 Bioteknologi (5 årig), Molekylærbiologi
URN: urn:nbn:no:ntnu:diva-18369Local ID: ntnudaim:6724OAI: diva2:565871
Available from: 2012-11-08 Created: 2012-11-08

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