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2019_Rabin_MasterThesis.pdf (935.08 KB)

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Percutaneous absorption and Skin accumulation of ABH Carbopol gel in Porcine Ear Skin

Neupane, Rabin
http://rave.ohiolink.edu/etdc/view?acc_num=mco1556641636092785

Abstract Details

2019, Master of Science (MS), University of Toledo, Pharmaceutical Sciences (Industrial Pharmacy).
Purpose A compounded Pluronic Lecithin Organogel (PLO gel) formulation of lorazepam (Ativan®), diphenhydramine hydrochloride (Benadryl®) and haloperidol (Haldol®) (ABH PLO gel) is used widely in relieving chemotherapy-induced nausea and vomiting (CINV) for the terminally ill hospice patient because of its presumed efficacy and low cost. In a recent study, Fletcher et al. conducted a randomized, double-blind, placebo-controlled, crossover, non-inferiority clinical trial using PLO-based ABH gel and concluded that it is not effective in the management of CINV [1]. In this study, we intended to prepare and evaluate the suitability of a hydroalcoholic Carbopol-based ABH gel (ABH Carbopol gel) for treating CINV. The permeation of lorazepam, diphenhydramine hydrochloride and haloperidol were hypothesized to be superior from ABH Carbopol gel compared to the ABH PLO gel. This project aimed to a) formulate an ABH Carbopol gel containing lorazepam, haloperidol and diphenhydramine and study the percutaneous absorption of drugs through Strat M™ membrane and porcine ear skin, and b) calculate the theoretical steady state concentration (CSS) of the drugs from the flux values. Methods The ABH Carbopol gel was prepared by dispersing 1.4% w/w of Carbopol 940 in water. The formulation comprised of ethanol, propylene glycol and ethoxydiglycol. The pH of formulation was adjusted to 6.8 using triethanolamine. The gel was characterized using pH meter, viscometer, differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Percutaneous absorption of ABH Carbopol gel was carried out across the porcine ear skin and Strat-M membrane in Franz cells. A validated HPLC method was used to determine the drug concentrations permeated at different time intervals. The recovery of drugs after the permeation study was carried out by analyzing the concentration of drug present in various compartments. Results The pH of the ABH Carbopol gel was found to be 6.80 ± 0.33. The retention time of diphenhydramine, haloperidol and lorazepam was found to be 4.72, 7.11 and 18.69 minutes, respectively. The DSC thermogram of ABH Carbopol gel showed the absence of characteristic drug peaks indicating the presence of drugs in the dissolved state. The mass balance of drugs was found between 90 to 110%. Theoretical steady state concentration (Css) of drugs was determined using flux values obtained from the permeation study. The theoretical Css values of diphenhydramine, haloperidol and lorazepam were found to be 7.44 ng/ml, 0.43 ng/ml and 3.35 ng/ml, respectively, which are much lower than the CSS required to achieve a treatment for CINV. Conclusion Based on the percutaneous absorption data, the ABH Carbopol gel failed to deliver the required therapeutic concentrations of the drugs for treating CINV.
Sai HS Boddu (Committee Chair)
Jerry Nesamony (Committee Member)
Gabriella Baki (Committee Member)
Pharmaceuticals
Transdermal system, Permeation enhancer, ABH gel, Carbopol gel

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Citations

  • Neupane, R. (2019). Percutaneous absorption and Skin accumulation of ABH Carbopol gel in Porcine Ear Skin [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1556641636092785

    APA Style (7th edition)

  • Neupane, Rabin. Percutaneous absorption and Skin accumulation of ABH Carbopol gel in Porcine Ear Skin. 2019. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1556641636092785.

    MLA Style (8th edition)

  • Neupane, Rabin. "Percutaneous absorption and Skin accumulation of ABH Carbopol gel in Porcine Ear Skin." Master's thesis, University of Toledo, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=mco1556641636092785

    Chicago Manual of Style (17th edition)

mco1556641636092785
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© 2019, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.