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dc.contributor.authorPuri, Ashana
dc.date.accessioned2019-05-06T12:28:19Z
dc.date.available2019-05-06T12:28:19Z
dc.identifier.urihttp://hdl.handle.net/10898/10071
dc.description.abstractTransdermal drug delivery, an attractive alternative to other routes of delivery, allows drugs to reach the systemic circulation by traversing the skin barrier. Skin, with a surface area of 1-2 sq.m, is a readily accessible route for local as well as systemic drug delivery. However, a major challenge encountered while developing a successful topical/transdermal drug delivery system is to ensure the penetration of drugs across the outermost lipophilic and dead layer of skin, the stratum corneum, which acts as a barrier to drug delivery. Moderately lipophilic (log P of 1-3), potent, and unionized drug molecules with a molecular weight of <500 Da and melting point <250 °C, tend to diffuse passively through the skin. However, hydrophilic drugs are unable to permeate through the passive route, and lipophilic drugs have tendency of forming depots in the stratum corneum. Thus, enhancement techniques are applied to facilitate delivery of desired therapeutic or prophylactically relevant doses of such actives, topically or transdermally. In the present study, chemical strategies such as addition of penetration enhancers in the drug formulations and/or physical technologies such as microneedles, anodal iontophoresis, and ablative laser were investigated for enhancement in delivery of cosmetic (epigallocatechin-3-gallate) as well as therapeutic (3-fluoroamphetamine) and prophylactic (antiretroviral agents: elvitegravir and tenofovir alafenamide) actives, into and across skin. Also, in vitro microdialysis was explored for simultaneous quantification of vertical and lateral rate of diffusion of diclofenac sodium as model drug, in intact as well as skin microporated with microneedles and laser. Furthermore, 7-day transdermal patches of tenofovir alafenamide, including various chemical enhancers were formulated and investigated for in vitro permeation across human epidermis. Overall, the chemical and physical enhancement techniques were found to significantly enhance the skin permeation of different actives, as compared to their respective passive treatments. Also, the microdialysis studies revealed significant enhancement in lateral and vertical diffusion of diclofenac sodium in dermatomed human skin porated with microneedles and ablative laser, as compared to intact skin. Furthermore, a 7-day suspension-based transdermal patch of tenofovir alafenamide that could successfully deliver the desired HIV prophylactic dose was developed.
dc.subjectMercer University -- Dissertations
dc.subjectCollege of Pharmacy
dc.titleEnhanced Delivery Of Actives Through Skin From Patches And Formulations, And Distribution Within And Across Skin
dc.typeText
dc.date.updated2019-05-03T20:12:41Z
dc.language.rfc3066en
refterms.dateFOA2020-09-29T13:42:40Z


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