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dc.creatorOguejiofor, Cosmas Joshua Nnabuezeen_US
dc.date.accessioned2004-10-21T00:08:42Zen_US
dc.date.accessioned2013-01-04T05:03:27Z
dc.date.available1996-01-01T08:00:00Zen_US
dc.date.available2013-01-04T05:03:27Z
dc.date.created1996-01en_US
dc.date.issued1996-01-01en_US
dc.date.submittedJanuary 1996en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-10212004-000842en_US
dc.description.abstractTransdermal delivery of Prostaglandin E1 (PGE1) would represent a significant improvement over the currently available injectable dosage forms in terms of reduced side effects and improved patient acceptance and compliance with therapy. PGE1 is a vasodilator and smooth muscle relaxer which is used in the treatment of erectile dysfunction and peripheral arterial occlusive disease. Human skin presents a significant barrier to most drugs which must be overcome for transdermal delivery to be achieved. Liposomes are novel drug delivery vehicles which can enhance transdermal delivery. The specific objectives of the thesis were therefore to develop a stable liposomal transdermal PGE1 formulation and to evaluate the potential for transdermal delivery of PGE1 by liposome encapsulation. Formulation optimization studies were carried out using nonliposomal and liposomal vehicles containing varying proportions of natural and synthetic lipids, viscosity enhancers, and skin penetration enhancers. Transdermal delivery profiles of the test formulations were determined using an in vitro flow-through diffusion cell model. Physical stability analyses of the liposomal formulations were obtained by carrying out organoleptic, microscopic, and encapsulation efficiency/leakage studies. Chemical stability analyses of PGE1 were conducted at 4°C and 37°C using novel high pressure liquid chromatography assays that were developed in the course of the thesis work. The in vitro tissue homogenate model was used to determine the metabolism of PGE1 in human foreskin, human placenta and rabbit lung being positive controls. In vivo transdermal PGE1 delivery studies were conducted by using (i) laser Doppler flowmetry in healthy volunteers and (ii) color Doppler ultrasonography/clinical trials in patients with erectile dysfunction, to monitor pharmacological and/or clinical effects following topical application of PGE1. The in vitro and in vivo transdermal delivery studies confirmed that PGE1 can be delivered through the skin using liposomes. Metabolism of PGE1 in human foreskin is low and is not likely to limit the transdermal delivery of PGE1. More research is warranted in order to translate the thesis findings into a commercial transdermal PGE1 product.en_US
dc.language.isoen_USen_US
dc.titleTransdermal delivery of prostaglandinsen_US
thesis.degree.departmentPharmacyen_US
thesis.degree.disciplinePharmacyen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US
dc.type.materialtexten_US
dc.type.genreThesisen_US
dc.contributor.committeeMemberFoldvari, Mariannaen_US


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