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Title: An investigation of the anti-inflammatory activity and gastro-toxicity of indomethacin (1%), ibuprofen (5%) and felbinac (3%) topical formulations using carrageenan-induced rat paw oedema and ultra-violet induced erythema models of inflammation
Author: Shergill, Sarbjit
Awarding Body: Liverpool John Moores University
Current Institution: Liverpool John Moores University
Date of Award: 1993
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Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used in the management of several rheumatic disorders. However, one of the major drawbacks to their use has been the severity of the adverse reactions, in particular the gastro-toxicity associated with oral administration. Topical formulations of NSAIDs were introduced in an attempt to overcome the systemically mediated gastro-toxic effects of oral delivery. It was claimed that topical delivery localised the drug at the site of action and therefore reduced the gastro-toxic effects. These claims were investigated, using carrageenan-induced rat paw oedema arid U.V.- induced erythema models of inflammation. The aim of this study was to determine whether the topical NSABD formulations under investigation produced their beneficial effects locally or systemically, and if topical delivery afforded any benefits with regard to gastro-toxicity. Following topical administration of the NSAID the drug did not remain localised within the tissue and the plasma drug levels achieved were comparable to those produced orally. Hence the number of lesions observed after topical administration were not significantly different to those caused by oral administration. In carrageenan-induced rat paw oedema plasma drug levels appeared to be a critical factor in producing a beneficial anti-inflammatory effect. However, in U.V.-induced erythema tissue drug levels relate to significant anti-inflammatory activity. Therefore, it can be concluded that the topical NSAID formulations under investigation appear to have both systemically arid locally mediated anti-inflammatory effects and that they do not afford any benefits in terms of reducing gastro-toxic effects. The site of action is probably dependent upon the type of end-point inflammatory response (oedema or erythema) and the mediators responsible for the inflammatory response.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available