Doungdaw Chantasart1, Jinsong Hao, S Kevin Li. 1. Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, 3225 Eden Avenue, 136 HPB, Cincinnati, Ohio 45267, USA.
Abstract
PURPOSE: β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. METHODS: Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. RESULTS: The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. CONCLUSIONS: The present results suggest the possibility of topical treatment of hemangioma using β-blockers.
PURPOSE: β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. METHODS: Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. RESULTS: The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. CONCLUSIONS: The present results suggest the possibility of topical treatment of hemangioma using β-blockers.
Authors: T J Franz; P A Lehman; S F Franz; H North-Root; J L Demetrulias; C K Kelling; S J Moloney; S D Gettings Journal: Fundam Appl Toxicol Date: 1993-08
Authors: Jillian G Baker; Christophe Fromont; Marjorie Bruder; Kevin S J Thompson; Barrie Kellam; Stephen J Hill; Sheila M Gardiner; Peter M Fischer Journal: ACS Pharmacol Transl Sci Date: 2020-07-01