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Dherya_Bahl_ETD_2017.pdf (2.29 MB)

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Design and Characterization of Topical Econazole Nitrate Formulations for Treating Raynaud’s Phenomenon

Bahl, Dherya
http://orcid.org/0000-0001-8612-8408
http://rave.ohiolink.edu/etdc/view?acc_num=mco1501518069682334

Abstract Details

2017, Master of Science in Pharmaceutical Science (MSP), University of Toledo, Pharmaceutical Sciences (Industrial Pharmacy).
Purpose: Raynaud’s phenomenon (RP) is characterized by multiple periodic or chronic ischemic or hypoxic attacks (vasospastic attacks) to distal arteries provoked by a drop in environmental temperature or emotional distress. An effective FDA approved first-line treatment of RP is still nonexistent. Preliminary studies indicate that the overexpression of transient receptor potential cation channel subfamily M member 8 (TRPM-8) results in increased cold sensitivity in RP subject’s skin, fibroblasts and endothelial cells and antagonizing this receptor protein might be a potential therapeutic approach for RP treatment. Econazole nitrate (EN), as a cold sensing TRPM-8 antagonist, could be used in treating RP. The purpose of this work was to design and characterize a novel topical formulation of EN for treating RP. Methods: Four topical dosage forms (F1_topical solution, F2_HPMC dispersion, F3_ VersaBase® cream and F4_Lipoderm® Activemax™ Cream) containing 3% w/w EN were prepared and characterized for drug content, pH, viscosity, spreadability, drug crystallinity and stability. In vitro permeation of EN from the formulations was carried out using Franz cells across pig ear skin and results were compared with the marketed EN cream. Results: All four formulations had desired physical and visual characteristics with 3% w/w EN. The pH of all formulations was found to be in between 4 and 5, with a drug content around 95%-105%. Viscosity and spreadability values for formulations F1, F2, F3 and F4 were 89.4, 1116, 20938, 6875 cps and 37.75, 24.89, 4.00 and 5.22 g.cm/sec, respectively. Based on the Franz cell study, the order of amount of drug permeated from highest to lowest was F2 (10.27%) > F4 (2.47%) > F1 (2.28%) > F3 (1.47%) > marketed formulation (0.22%). The measures of permeability and flux from highest to lowest were F2 > F4 > F1 > F3 > marketed formulation with a lag time of 3.93 h, 5.85 h, 5.16 h, 6.04 h and 5.88 h, respectively. Formulation F2 showed better penetration of the drug into the stratum corneum, epidermis and dermis layers. The drug concentration in the stratum corneum and epidermis was approximately 10-20 times higher from F2 compared to the marketed formulation. All formulations were found to be physically and chemically stable for up to 6 months. Conclusions: All four EN formulations were found to be better in terms of penetration into the skin layers, permeation across the skin with enhanced flux values and an evidently lowered onset of action compared to the 1% marketed cream. Formulation F2-HPMC dispersion could be further studied as a treatment option for RP.
Sai HS. Boddu (Committee Chair)
Jerry Nesamony (Committee Member)
Caren Steinmiller (Committee Member)
106 p.
Medicine; Pharmaceuticals
Raynauds Phenomenon; Cold Exposure; Vasospasm; TRPM-8; Econazole Nitrate; HPMC; DMSO; Topical; Permeation; Flux; Lag-time

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Citations

  • Bahl, D. (2017). Design and Characterization of Topical Econazole Nitrate Formulations 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=mco1501518069682334

    APA Style (7th edition)

  • Bahl, Dherya. Design and Characterization of Topical Econazole Nitrate Formulations 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=mco1501518069682334.

    MLA Style (8th edition)

  • Bahl, Dherya. "Design and Characterization of Topical Econazole Nitrate Formulations for Treating Raynaud’s Phenomenon." Master's thesis, University of Toledo, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=mco1501518069682334

    Chicago Manual of Style (17th edition)

mco1501518069682334
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© 2017, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.