Date of Award

2002

Degree Type

Thesis

Degree Name

Master of Science in Applied Pharmaceutical Sciences

Department

Applied Pharmaceutical Sciences

First Advisor

Hossein Zia

Abstract

Among various nonsteroidal anti-inflammatory drugs (NSAIDs), ketorolac tromethamine has been widely used for post operative and emergency treatment of pain. However, it accompanies adverse side effects including gastrointestinal irritation when administered orally. Topical administration of ketorolac offers the advantage of enhanced drug delivery to the affected sites with a reduced incidence of gastrointestinal side effects. However, as skin is an exceptionally effective barrier to most chemicals, very few drugs can permeate it in amounts sufficient to deliver a therapeutic dose. Therefore, systems that make the skin locally more permeable and thereby enable transdermal delivery are of great interest. Lecithin organogels are an example of such systems in which solutions of lecithin in organic solvents can be transformed into transparent gels by addition of a critical amount of water. The main objective of this study was to investigate lecithin organogels as carriers for topical application of ketorolac tromethamine. In this research, phase studies were carried out to obtain the concentration of components for the existence range of organogel and the effect of these additives on release rate of ketorolac was also evaluated through the artificial membranes and guinea pig skin. As the lecithin concentration was increased from 40 to 50 and then 60% w/w in formulations, a significant decrease in ketorolac release was obtained. A significant increase in drug release was also observed in formulations containing 6.5% w/w of ketorolac compared to those containing 1 % w/w of the drug. Increasing the water content of the organogels also resulted in an increase in ketorolac release. The optimum formulation of the organogel composed of 40% lecithin, 60% IPM containing 0.6% w/w of water and 6.5% w/w of ketorolac tromethamine showed the highest drug release rate. Moreover, the viscosity of the different formulations and their rheological behavior were also determined. All formulations showed a slight rheopexy behavior rheogram. It was found that increase in lecithin concentration resulted in an increase in the viscosity of the organogel. Overall, the results have suggested that ketorolac tromethamine could be incorporated with high concentrations into lecithin organogels which makes them interesting for use as a drug delivery vehicle for water soluble drugs.

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