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dc.contributor.authorBeebeejaun, Mubinah Thara
dc.description.abstractIn the treatment of inflammatory skin conditions patients are often prescribed more than one topical product: a topical corticosteroid (TCS), an emollient and a topical antibiotic in cases of clinically infected skin. Despite widespread prescribing, there exists a remarkable lack of consensus between healthcare bodies on the optimum application protocol for the products, with recommendations made on the basis of clinical ‘expert’ opinion rather than evidence-based findings. Thus, the aim of this thesis was to evaluate the impact of clinical application protocols on the in vitro percutaneous absorption and skin retention of TCSs and topical antibiotics. A two component model was initially employed where the model TCSs (Elocon cream and Dermovate cream) were applied before or after six emollients, with a five or thirty minute interval. The Aron mix, a tailored extemporaneous therapy, was subsequently investigated to confirm whether the trends observed with TCSs and emollients were applicable to further complex mixtures of a topical antibiotic (Fucidin cream) and a TCS (Diprosone cream) substantially diluted in an emollient base (Diprobase cream). The findings demonstrated that applying multiple topical products to the skin can induce rapid formulation changes in situ or indeed in the extemporaneously prepared Aron mix, resulting in an altered performance of the medicinal products in a formulation specific manner. Mixing of the TCSs or topical antibiotic with an emollient dissimilar to the product base resulted in a multitude of effects including alterations in drug and solvent thermodynamic activities, rapid drug crystallisation and emollient excipients acting with penetration enhancing effects. Complementary drug stability investigations of the extemporaneous Aron mix did not support the typically recommended shelf life for the product (two weeks to one month), with significant decreases in drug content evident after seven days. In disagreement with clinical recommendations for TCSs and emollients, allowing up to thirty minutes between product applications was not sufficient to mitigate emollient effects on TCS drug delivery to the skin. Furthermore, application of the TCS after the emollient largely decreases drug delivery to the skin up to 4.4 fold compared to the TCS alone, findings which counter the clinical opinion that application of a TCS to well moisturised skin can increase drug delivery. Overall, the work presented in this thesis delivers a body of evidence previously unreported to suggest that applying multiple topical products to the skin at similar times may significantly alter the critical quality attributes of the product(s) to unpredictable extents and upon further investigation, these findings will support the advancement of conclusive clinical guidance.en_US
dc.rightsAttribution 3.0 United States*
dc.subjecttopical corticosteroiden_US
dc.subjectskin permeationen_US
dc.subjectapplication protocolsen_US
dc.titleThe Impact of Clinical Application Protocols for Multiple Topical Products on Drug Delivery to the Skinen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US

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