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dc.contributor.advisorParsons, Daniel L.
dc.contributor.advisorRamapuram, Jayachandra B.
dc.contributor.authorChadha, Gurkishan
dc.date.accessioned2009-07-13T16:00:44Z
dc.date.available2009-07-13T16:00:44Z
dc.date.issued2009-07-13T16:00:44Z
dc.identifier.urihttp://hdl.handle.net/10415/1778
dc.description.abstractGenistein is a soy isoflavone and it is a chemo preventative agent against various cancer cell lines including melanoma. The percutaneous absorption of genistein has been scantly investigated. Also, genistein has very poor skin permeability characteristics. The main objective of this study was to formulate genistein as a topical gel, and incorporate various penetration enhancers like terpenes and glycol derivatives, in it to increase the retention and the permeation of genistein through the skin. Methocel® E4M was found to formulate a stable and homogenous gel with genistein. It had a better skin permeation and retention as compared to the gels formulated from Pluronic® F-127 NF and Carbopol® 934 NF polymers. Genistein is a highly lipophilic drug and its log octanol-water partition coefficient (log P) was determined to be 2.94. The drug was solubilized in ethanol, but when the gel was made, the drug was precipitated as fine particle dispersion. With the drug in the form of dispersion, it was possible to determine the solubility of genistein in the various formulations. It was observed that formulations containing terpenes had similar solubility for genistein as compared to Methocel gel, except for Carvone which had increased solubility (1.5 fold). Although the solubility was similar, yet the permeability constants were significantly higher than the control formulation (P < 0.05). Menthol and limonene showed 9 and 7 fold increase, respectively. On the other hand, the formulations containing various glycol derivatives had decreased solubility for genistein (6-8 folds), yet had much larger permeability constant (P < 0.05). This can be associated with the fact that glycol derivative formulations had a much lesser amount of alcohol as compared to the Methocel gel, thus the solubility of Methocel gel containing ethanol was higher. For use in percutaneous absorption experiments, the HPLC method of genistein was validated for its precision and accuracy. The percentage coefficient of variance (%CV) for intra-day and inter-day precision was 0.44% and 0.67%, respectively. Furthermore, forced degradation studies were performed on genistein to determine its stability under various stress conditions. Genistein was found to be stable in neutral and 1.5% w/w H2O2 solution, while it had 80% degradation in the presence of 1N NaOH (24 hours), and 1N HCl (5 days). In conclusion, genistein was formulated with various penetration enhancers for increasing the permeation and drug retention in human skin. Based on the permeation and skin retention data, it was found that menthol, Lauroglycol® 90, Labrasol® and Transcutol® P were most efficient in enhancing the skin permeation and retention of genistein. The gel having sufficient skin retention for genistein, would act as a promising chemoprotective agent against melanoma. These formulations also will have a potential for the use as anti-aging products.en
dc.rightsEMBARGO_NOT_AUBURNen
dc.subjectPharmacal Sciencesen
dc.titleTransdermal Delivery of Genistein as a Chemoprotective Drug for Melanomaen
dc.typethesisen
dc.embargo.lengthNO_RESTRICTIONen_US
dc.embargo.statusNOT_EMBARGOEDen_US


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