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Percutaneous Absorption of Lorazepam, Diphenhydramine Hydrochloride, and Haloperidol from ABH Gel

Author(s):  Dahal Amit, Neupane Rabin, Boddu Sai HS, Renukuntla Jwala, Khupse Rahul, Dudley Richard

Issue:  Mar/Apr 2020 - Volume 24, Number 2
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Abstract:  The objective of this project was to study the percutaneous absorption of lorazepam, diphenhydramine hydrochloride, and haloperidol from a topical Pluronic lecithin organogel, also known as ABH gel, across the porcine ear skin and verify its suitability for topical application. ABH gel was prepared using lecithin in isopropyl palmitate solution (1:1) as an oil phase and 20% w/v Poloxamer 407 solution as an aqueous phase. The gel was characterized for pH, viscosity, drug content, and thermal behavior. A robust high-performance liquid chromatography method was developed and validated for simultaneous analysis of lorazepam, diphenhydramine hydrochloride, and haloperidol. The percutaneous absorption of lorazepam, diphenhydramine hydrochloride, and haloperidol from ABH gel was carried out using Franz cells across the Strat-M membrane and pig ear skin. The pH of ABH gel was found to be 5.66 ± 0.13. The retention time of diphenhydramine hydrochloride, haloperidol, and lorazepam was found to be 5.2 minutes, 7.8 minutes, and 18.9 minutes, respectively. The ABH gel was found to be stable for up to 30 days. Theoretical steady state plasma concentrations (CSS) of diphenhydramine hydrochloride, haloperidol, and lorazepam calculated from flux values were found to be 1.6 ng/mL, 0.13 ng/mL, and 2.30 ng/mL, respectively. The theoretical CSS of diphenhydramine hydrochloride, haloperidol, and lorazepam were much lower than required therapeutic concentrations for antiemetic activity to relieve chemotherapy-induced nausea and vomiting. From the percutaneous absorption data, it was evident that ABH gel failed to achieve required systemic levels of lorazepam, diphenhydramine hydrochloride, and haloperidol following topical application.

Related Keywords: Amit Dahal, MS, Rabin Neupane, MS, Sai HS. Boddu, PhD, Jwala Renukuntla, PhD, Rahul Khupse, PhD, Richard Dudley, PhD, lorazepam, diphenhydramine hydrochloride, haloperidol, percutaneous absorption, transdermal administration, skin penetration, dermal permeability, ABH gel, drug cost, topical preparation, chemotherapy-induced nausea and vomiting, cancer patients, emesis, pluronic lecithin organogels, PLO gels, palliative care, hospice, drug permeation, penetration enhancers

Related Categories: CANCER AND AIDS, EXCIPIENTS, GASTROENTEROLOGY, PEER-REVIEWED, DOSAGE FORMS/DRUG CARRIERS, NEUROLOGY

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