April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
In vitro Human Corneal Epithelial Cell Culture Model for Evaluating Formulation Effects on Ocular Permeability
Author Affiliations & Notes
  • J. Shen
    Allergan, Irvine, California
  • W. Chang
    Allergan, Irvine, California
  • A. Kulkarni
    Allergan, Irvine, California
  • A. Weber
    Allergan, Irvine, California
  • Q.-C. Thai
    Allergan, Irvine, California
  • D. Welty
    Allergan, Irvine, California
  • Footnotes
    Commercial Relationships  J. Shen, None; W. Chang, None; A. Kulkarni, None; A. Weber, None; Q.-C. Thai, None; D. Welty, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2436. doi:
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      J. Shen, W. Chang, A. Kulkarni, A. Weber, Q.-C. Thai, D. Welty; In vitro Human Corneal Epithelial Cell Culture Model for Evaluating Formulation Effects on Ocular Permeability. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2436.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : The assessment of corneal penetration is crucial for the development of topical ophthalmic medications. In this study, we evaluated the utility of the Clonetics® human corneal epithelial cell culture model as a tool for formulation screening to identify optimized formulations before proceeding with in vivo studies.

Methods: : Two in vitro formulation screening studies for compounds A and B were conducted using the human cell culture model. The in vitro results were compared to aqueous humor concentrations of A and B in rabbit following topical administration in vivo. The cells were monitored for transepithelial electrical resistance (TEER) values before and after treatment to assess integrity of the cell layer throughout the course of the study. All analytes were measured by LC-MS/MS.

Results: : The apparent permeability of Compound A across the human corneal epithelial cells was approximately 25% lower in formulation 2 compared to formulation 1. The corresponding in vivo rabbit aqueous humor exposure (Cmax and AUC0-4hr) was approximately 35-40% lower. For compound B, increasing the formulation pH from 6.0 to 7.0 to 8.0 resulted in approximately 4.5 and 9.5 times higher permeability of compound B, respectively. In vivo, the rabbit aqueous humor exposure (Cmax and AUC0-8hr) was approximately 4.76 - 5.65 fold higher following administration of pH 7.4 formulation compared to the pH 6.0 formulation.

Conclusions: : The Clonetics® human corneal epithelial cell culture is a useful in vitro model for assessing the corneal penetration of ophthalmic drug candidates and to elucidate the effects of formulation on the permeability of drug candidates.

Keywords: cornea: epithelium 

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