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Ultrasound-mediated Topical Delivery of Econazole nitrate for Treating Raynaud’s Phenomenon

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2017, Master of Science in Pharmaceutical Science (MSP), University of Toledo, Pharmaceutical Sciences (Industrial Pharmacy).
Objectives: The focus of this investigation was to assess the ultrasound-assisted econazole nitrate (EN) permeation from topically applied formulations for treating Raynaud’s phenomenon. The aims of this study were i) to identify the optimal ultrasound parameters for the percutaneous absorption of EN, ii) to assess the in vitro percutaneous absorption of EN and toxicity in the porcine ear skin from different topical formulations following ultrasound application. Methods: Optimization of ultrasound parameters such as the distance of the horn, application time and amplitude were performed. In vitro percutaneous absorption studies were performed using different EN formulations (F1_solution, F2_HPMC dispersion, F3_Lipoderm® Activemax™ Cream and F4_Versabase® cream) across ultrasound-treated porcine skin and were compared with the control group (skin samples without ultrasound treatment). Histological evaluation using hematoxylin and eosin stain was carried out to assess the dermal toxicity of formulations and ultrasound exposure. To further support the findings of ultrasound-assisted drug permeation studies, ATR-FTIR was performed to investigate the effect of ultrasound on the conformational changes in stratum corneum lipids characterized by the changes in spectral shifts. Results: A constant frequency (20 kHz) ultrasound application with 40% amplitude, 0.5cm distance between ultrasound horn and skin surface for 2 minutes was optimized. The permeation of EN was found to be higher from ultrasound- treated skin samples than the control group. Drug permeation from F2_HPMC dispersion was found to be higher as compared to other formulations and the marketed cream. The lag time of ultrasound- treated skin samples were found to be significantly lower than the control. Histological evaluation confirmed that HPMC dispersion showed no signs of toxicity. ATR-FTIR studies revealed a slight increase in the -CH2- stretching vibrations (~ 2920 cm-1 and 2850 cm-1) in ultrasound-treated skin samples as compared with control. This confirms the reversible conformational changes in the stratum corneum lipids, thereby enhancing the drug permeabilization. Conclusions: The ultrasound-assisted topical delivery of F2_HPMC dispersion could be explored as a new strategy for treating Raynaud’s phenomenon.
Sai HS Boddu, PhD (Committee Chair)
116 p.

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Citations

  • Daftardar, S. B. (2017). Ultrasound-mediated Topical Delivery of Econazole nitrate for Treating Raynaud’s Phenomenon [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1501501075880616

    APA Style (7th edition)

  • Daftardar, Saloni. Ultrasound-mediated Topical Delivery of Econazole nitrate for Treating Raynaud’s Phenomenon. 2017. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1501501075880616.

    MLA Style (8th edition)

  • Daftardar, Saloni. "Ultrasound-mediated Topical Delivery of Econazole nitrate for Treating Raynaud’s Phenomenon." Master's thesis, University of Toledo, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=mco1501501075880616

    Chicago Manual of Style (17th edition)