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Effect of Chitosans and Other Excipients on the Permeation of Ketotifen, FITC-Dextran, and Rhodamine 123 through Caco-2 Cells

SRI International, Menlo Park, CA 94025, USA

M. Sou

Novartis Corporation, Paramus, NJ, USA

A.N. Uddin

Emipshere Technologies, Tarrytown, NY, USA

S.G. Gayakwad

Department of Pharmaceutical Sciences, Mercer University Atlanta, GA 30341, USA

M.J. D'Souza

Department of Pharmaceutical Sciences, Mercer University Atlanta, GA 30341, USA, dsouza_mj{at}mercer.edu

The determination of drug permeability is an important part of formulation, development, and studying the effect of excipients on drug delivery processes. Ketotifen, FITC-labeled dextran, and Rhodamine 123 permeation was evaluated across Caco-2 cells grown on permeable inserts in the presence of chitosan, N,O-carboxymethyl chitosan (NOCC), Carbopol 934P, Polysorbate 80, and Disodium edetate. Samples with chitosan decrease in transepithelial electrical resistance in a concentration dependent manner not seen with the other excipients used. This corresponds with significant improvement of paracellular permeation of FITC-dextran and Rhodamine 123 compared to the control (p<0.005) but Ketotifen permeation with chitosan does not show statistically significant improvement as compared to the control. Although Rhodamine 123 is a known p-glycoprotein substrate, this data would indicate that the p-glycoprotein transport system is not the rate limiting factor in Rhodamine 123 permeation. Ketotifen permeation is improved slightly in the presence of NOCC, Polysorbate 80, and Disodium edetate. These excipients have been associated with improved transcellular permeation. Carbopol 934P does not improve any of the drug models' permeation. These results clearly show the effectiveness of using Caco-2 cells for screening formulations and excipients for drug development.

Key Words: chitosan • Caco-2 cells • Ketotifen • Rhodamine 123 • drug permeability • determining drug permeability • drug permeability screen • in vitro permeability screen.

Journal of Bioactive and Compatible Polymers, Vol. 23, No. 2, 187-202 (2008)
DOI: 10.1177/0883911507088399


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