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University of Arizona

1. Aodah, Alhassan. Preformulation and Topical Penetration Studies .

Degree: 2017, University of Arizona

Chapter I: preformulation studies on piperlongumine Piperlongumine is a natural alkaloid extracted from piper plant which has been used traditionally for the treatment of certain diseases. This compound shows interesting in-vitro pharmacological activity such as selective anticancer activity and higher cytotoxicity than methotrexate, cyclophosphamide and adriamycin on breast, colon, and osteosarcoma cancers, respectively. However, the physicochemical properties of this compound have not been well characterized. In this research, preformulation studies for piperlongumine have been performed to determine factors which influence solubility and stability which, in turn, can be used to assist future formulation development. The solubility of piperlongumine in water was found to be approximately 26 μg/ml. Using 10% polysorbate 80 as a surfactant resulted in a 27 fold increase in solubility. Cosolvents and cyclodextrins afforded concentrations of 1 mg/ml and higher. The pH degradation rate profile for piperlongumine at various temperatures shows significant instability of the drug at pH values 7 and 3, and maximum stability around pH 4. It was estimated that it would take approximately 17 weeks for piperlongumine to degrade by 10% at 25°C, pH 4. Additionally, piperlongumine showed marked photo-degradation upon exposure to an ultraviolet light source, especially in aqueous media. Chapter II: preformulation and evaluation of resatorvid topical delivery Resatorvid is a small molecule shows interesting anti- inflammatory biological activity. The clinical trial was conducted for sepsis-induced cardiovascular and respiratory failure, but it was terminated due to low efficacy. Further researches show a different biological activity of resatorvid such as its activity against UV-induced skin cancer. The goal of this study is to determine some important physiochemical properties of resatorvid, as well as intrinsic penetration criteria through the murine skin, either ex-vivo or in-vivo. Intrinsic water solubility of resatorvid was found to be 95.32± 1.75 ug/ml and could be duplicated by using 10 % ethanol as cosolvent. The pH solubility profile shows the acidic pka value of resatorvid is around 8-8.1. Photo-stability results indicate more stability in non-aqueous more than aqueous medium. Resatorvid pH degradation rate profiles indicate the maximum stability between pH3 -5 and maximum instability at pH 8 and 9 at all experimental temperatures over 26 days. T90 at 25 °C was 648 days in pH 3 versus 11 days in pH 9. Ex-vivo penetration evaluation for resatorvid through hairless murine skin was evaluated using acetone and phosphate buffer formulations. The flux values were 0.82 and 0.36 for acetone and phosphate buffer formulation respectively. The percent of drug retention in the dermis layer of skin were also evaluated and found to be 37.99% for the acetone formulation and 21.13 % for phosphate buffer formulation. The in-vivo penetration evaluation study was performed by topically applying of resatorvid in acetone solution. Skin biopsy… Advisors/Committee Members: Myrdal, Paul B (advisor), Myrdal, Paul B. (committeemember), Yalkowsky, Samuel H. (committeemember), Mayersohn, Michael (committeemember), Mansour, Heidi M. (committeemember).

Subjects/Keywords: Resatorvid; Strat-M

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APA (6th Edition):

Aodah, A. (2017). Preformulation and Topical Penetration Studies . (Doctoral Dissertation). University of Arizona. Retrieved from

Chicago Manual of Style (16th Edition):

Aodah, Alhassan. “Preformulation and Topical Penetration Studies .” 2017. Doctoral Dissertation, University of Arizona. Accessed January 18, 2020.

MLA Handbook (7th Edition):

Aodah, Alhassan. “Preformulation and Topical Penetration Studies .” 2017. Web. 18 Jan 2020.


Aodah A. Preformulation and Topical Penetration Studies . [Internet] [Doctoral dissertation]. University of Arizona; 2017. [cited 2020 Jan 18]. Available from:

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Aodah A. Preformulation and Topical Penetration Studies . [Doctoral Dissertation]. University of Arizona; 2017. Available from: