title: Evaluation of β-blocker gel and effect of dosing volume for topical delivery.
abstract: Although topical administration of β-blockers is desired because of the improved therapeutic efficacy and reduced systemic adverse effects compared with systemic administration in the treatment of infantile hemangioma, the permeation of β-blockers across skin under finite dose conditions has not been systematically studied and an effective topical β-blocker formulation for skin application is not available. The present study evaluated the permeation of β-blockers propranolol, betaxolol, and timolol across human epidermal membrane (HEM) from a topical gel in Franz diffusion cells in vitro under various dosing conditions. The effects of occlusion and dosing volume on percutaneous absorption of β-blockers from the gel were studied. The permeation data were compared with those of finite dose diffusion theory. The results showed that skin permeation of β-blockers generally could be enhanced two to three times by skin occlusion. The cumulative amounts of β-blockers permeated across HEM increased with increasing dosing volume. An adequate fit was obtained between the theoretical curve and experimental permeation data, indicating that the experimental results of the gel are consistent with finite dose diffusion theory. In conclusion, the findings suggest the feasibility of using topical gels of β-blockers for infantile hemangioma treatment and topical application with skin occlusion is preferred.
authors.affiliation: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, 45267.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Doungdaw
authors.initials: D
authors.lastname: Chantasart
authors.forename: S Kevin
authors.initials: SK
authors.lastname: Li
mesh_terms: D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005782:Gels / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D005782:Gels
keywords: diffusion; finite dose; hemangioma; occlusion; partition coefficient; percutaneous; skin; stability; topical; β-blocker