الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
For poorly soluble drugs, the rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Therefore the dissolution behaviour of a together with the solubility of the drug are key determinant of its oral bioavailability. There have been numerous efforts to improve drug dissolution rate. These include, reducing particle size to increase surface area, thus increasing dissolution rate of drug, solubilization in surfactant systems ,formation of water soluble complexes, use of prodrug and drug
derivatives and decreasing crystallinity of drug substance through formation of solid
dispersions with different additives including cyclodextrins and their derivatives.
The thesis started with a short summary of methods for improving solubility, complexation with cyclodextrins and their applications.
Celecoxib and meloxicam, two widely used anti-inflammatory drugs, were used. Their undesirable physical properties may increase the incidence of irritating side effects on the gastrointestinal tract because of a prolonged contact time with the mucosa. Numerous attempts have been made to improve the dissolution rate of these widely used antirheumatic agents, to obtain more rapid and complete absorption.
The attempts in this study were targeted to formulate better soluble dispersions of these drugs using different approaches, mainly, complexation with HP3CD.
Part one: Enhancement of the dissolution rate of celecoxib using solid dispersion techniques
Part I aimed to enhance celecoxib solubility and hence its dissolution rate for better bioavailability.
Celecoxib, is a nonsteroidal anti-inflammatory drug, is the first selective cyclooxygenase2 (cox-2) inhibitor and also indicated as an adjuvant in the treatment of familial adenomatous polyposis. In spite of its high gastrointestinal (GI) permeability, celecoxib shows incomplete and poor oral bioavailability. This could be attributed to its low aqueous solubility, which leads to its inadequate dissolution in GI fluids and hence poor absorption. distribution, and target organ delivery. Iniprovement of aqueous solubility in such a case is a valuable goal to improve therapeutic efficacy. One of the most effective approaches is the preparation of solid dispersions using solvent evaporation technique. Many additives are used in this part including acdisol , aerosil 200 and urea. Itis observed that a slight increase in the dissolution rate of celecoxib can be obtained by formation of solid dispersion w ith t hese a dditives. T he s olubilization e fficiency is m ore favourable as the concentration of these carriers increased. The increase in the release with different carriers was found to be in the following order: urea >aerosil 200> acdisol.
In the pharmaceutical field, cyciodextrins (CDs) have been recognized as potent candidates to overcome the undesirable properties of drug molecules through the formation of inclusion complexes, in which each guest molecule is surrounded by the hyDROPhobic environment of the CD cavity. This can lead to the alteration of physicochemical properties of guest molecules.