الفهرس 
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Abstract
Ketoprofen (KPF) is one of the widely used non-steroidal anti- inflammatory drugs (NSAIDs) which is widely used in the treatment of rheumatic disorders and other chronic inflammatory diseases. KPF causes gastric irritation and is extensively metabolized in the liver. Administration of KPF via transdermal route can bypass these disadvantages and may maintain relatively consistent plasma levels. KPF is practically insoluble in water and the barrier function of the skin limits its formulation as a transdermal dosage form and makes this challenging. Hence in the present study attempt has been made to improve its penetration across skin. The aim of this thesis was to incorporate the drug in different gel formulae using different polymers with and without permeation enhancers and to study the effect of drug modification and vehicle modification on the release and permeation of gels. Therefore, the work of this thesis was divided into:
Preformulation Studies of Ketoprofen: Preformulation studies included partition coefficient determination, melting point determination, solubility analysis and compatibility studies. from the obtained results, one can conclude that; KPF is a good candidate for transdermal drug delivery. The aqueous solubility of KPF increased as a function of increasing the concentration of both permeation enhancers and carriers. There is no interaction between KPF and the employed excipients according to IR study.
Formulation and release studies using tea bags: The effect of the employed gel bases and the permeation enhancers on the release profiles of KPF was studied. from the obtained results, one can conclude that methyl cellulose (MC) polymer achieved the highest release. KPF release decreased as the concentration of the polymer increased .However; it increased in the presence of permeation enhancers (higher from Tween 80).
Release studies with cellophane membrane and rat skin: The objective was to determine the release of KPF transdermal gel bases through cellophane membrane and their permeation through rat skin. The effect of the employed gel bases and the permeation enhancers on the permeation profiles of KPF was studied. The correlation between in-vitro drug release and permeation was also studied. from the obtained results, one can conclude that MC polymer achieved the highest release and permeation. There is an increase in the release and permeation rate of KPF in presence of permeation enhancers (higher from Tween 80). There is a strong correlation between in-vitro release and permeation of all KPF gel formulae.
Evaluation of transdermal delivery systems: Evaluation of clarity, homogeneity, spreadability, extrudability, pH ,drug content and rheological properties of KPF gel bases was performed .from the obtained results, one can conclude that all the prepared gel formulae were smooth and homogenous in appearance, good spreadability and extrudability. pH and drug content were within the required range. KPF gel formulae have pseudoplastic flow and thixtropic behaviors.
Stability studies: The stability of transdermal gel bases was studied at 5°C and at room temperature (25°C) for 6 months. from the obtained results, one can conclude that the degradation of KPF was very slow at all temperatures chosen which indicated its chemical stability. from all the previous tests, F16 (2.5%KPF+5%MC+5%Tween 80) was chosen as the best formula for studying the effect of drug and vehicle modification on gel behavior.
Studying the effect of drug modification on gel behavior: The effect of drug modification (as solid dispersion and niosomes ) on the in-vitro release and permeation profiles of KPF was studied. from the obtained results, one can conclude that the release and permeation of solid dispersion gels were higher than F16 and were higher from HPβCD. The release and permeation of niosomal gels were lower than F16 and were more retarded from Span 60.
Studying the effect of vehicle modification on gel behavior: Modifications of vehicle into thermosensitive poloxamer gel and eudragit organogel was performed by changing the cellulosic polymer. The effect of vehicle modification on the in-vitro release and permeation profiles of KPF was studied. from the obtained results, one can conclude that Poloxamer gels have the ability to form gel in the range of body temperature. As poloxamer and eudrgit concentration increased, release and permeation decreased. % KPF released and permeated from P1, P2, E1 and E2 were higher than that from F16. However, % KPF released or permeated from P3 and E3 was lower than F16.
In-vivo studies:In-vivo studies involving skin irritation test, Pharmacodynamic study and pharmacokinetic study were performed. from the obtained results, one can conclude that all the studied gel formulae did not show any irritation. All the studied transdermal formulae have a good analgesic effect, enhanced bioavilability and sustained plasma drug concentration with clear significant difference from control one.