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Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

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Abstract

Hydroxyzine, an effective but sedating H1-antihistamine is given orally to treat allergic skin disorders. This study was performed to assess the peripheral H1-antihistaminic activity and extent of systemic absorption of hydroxyzine from liposomes applied to the skin. Using L-α-phosphatidylcholine (PC), small unilamellar vesicles (SUVs) and multilamellar vesicles (MLVs) containing hydroxyzine were prepared. Hydroxyzine in Glaxal Base (GB) was used as the control. Using a randomized, crossover design, each formulation, containing 10 mg of hydroxyzine, was applied to the shaved backs of 6 rabbits (3.08±0.05 kg). Histamine-induced wheal tests and blood sampling were performed at designated time intervals up to 24 hours. Compared with baseline, hydroxyzine from all formulations significantly suppressed histamine-induced wheal formation by 75% to 95% for up to 24 hours. Mean maximum suppression, 85% to 94%, occurred from 2 to 6 hours, with no differences among the formulations. The areas of plasma hydroxyzine concentration versus time area under the curve (AUCs) from PC-SUV and PC-MLV, 80.1±20.8 and 78.4±33.9 ng/mL/h, respectively, were lower than that from GB, 492±141 ng/mL/h (P<.05) over 24 hours. Plasma concentrations of cetirizine arising in-vivo as the active metabolite of hydroxyzine, from PC-SUV, PC-MLV, and GB, were similar with AUCs of 765±50, 1035±202, and 957±227 ng/mL/h, respectively (P<.05). Only 0.02% to 0.06% of the initial hydroxyzine dose remained on the skin after 24 hours. In this model, hydroxyzine from SUV and MLV had excellent topical H1-antihistaminic activity, and minimal systemic exposure occurred. Cetirizine formed in-vivo contributed to some of H1-antihistaminic activity.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Manitoba, Pharmacy Building, Room 202, 50 Sifton Road, R3T 2N2, Winnipeg, MB, Canada

    Abeer A W Elzainy, Xiaochen Gu & Keith J. Simons

  2. Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    F. Estelle R. Simons & Keith J. Simons

Authors
  1. Abeer A W Elzainy
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  2. Xiaochen Gu
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  3. F. Estelle R. Simons
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  4. Keith J. Simons
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Correspondence to Keith J. Simons.

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Published: November 5, 2003

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Elzainy, A.A.W., Gu, X., Simons, F.E.R. et al. Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model. AAPS PharmSci 5, 28 (2003). https://doi.org/10.1208/ps050428

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  • DOI: https://doi.org/10.1208/ps050428

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