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• W2040287517 abstract "Abstract The buccal absorption characteristics and physicochemical properties of the β-adrenoceptor blocking agents propranolol and atenolol have been investigated to evaluate their permeation properties across biological lipid membranes. The dissociation constants, solubilities of free base, and n-heptane partition coefficients show that propranolol in its unionized form is much more lipophilic than atenolol, both drugs being bases with a similar pKa. Buccal absorption was studied under conditions of varying drug concentration, contact time, and pH, and controlled through the use of a non-absorbable marker. The absorption findings are in general agreement with the pH-partition theory. A new compartmental diffusional model that includes membrane storage and a hypothetical ‘aqueous pH-buffering surface system’ allowed a more exhaustive interpretation to be made. A method for the estimation of the intrinsic pH and buffer capacity of the postulated surface system from drug pH-absorption data and partition coefficients alone is described. With human oral mucosa the intrinsic pH was near 6·7, and the buffering capacity of the system (expressed as the ratio ΔpH/ΔpH eff) about 2·86. The method was validated using published absorption data from the rat small intestine. Absorption of unionized drug through pores is shown to be negligible in the buccal absorption situation. The time course of absorption suggests membrane storage of lipophilic compounds; the in vivo partition coefficient of unionized propranolol relative to the mucous membrane could be calculated for the peusdo-steady state of absorption, i.e. the partition equilibrium between mouth content and membrane, to be approximately 776; this value is of the same order as the in vitro partition coefficient for the erythrocyte/plasma system. The lipid biophase of the buccal membrane is estimated semiquantitatively to be of intermediate polarity (ɛ = 3–4)." @default.
• W2040287517 created "2016-06-24" @default.
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• W2040287517 date "1978-09-01" @default.
• W2040287517 modified "2023-09-27" @default.
• W2040287517 title "A membrane model of the human oral mucosa as derived from buccal absorption performance and physicochemical properties of the β-blocking drugs atenolol and propranolol" @default.
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• W2040287517 doi "https://doi.org/10.1111/j.2042-7158.1978.tb13185.x" @default.
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