title: Evaluating the Transport Kinetics of a Model Compound Released From Cellulosic Coacervate Compositions Into Artificial Sebum.
abstract: Complex coacervates of cationic polymers and anionic surfactants, which are produced spontaneously during the use of rinse-off formulations, represent an important delivery vehicle for topical agents to the skin surface and appendages. In this study, an artificial sebum-loaded cell culture insert method for determining the sebum diffusion properties of topical agents was optimized for in vitro release testing. This method was subsequently used to evaluate the transport kinetics of a model compound, kinetin, released from semi-solid coacervate formulations into sebum. Coacervate compositions were prepared with cationic-hydroxyethyl cellulose dodecyl sulfate (cat-HECDS), sodium dodecyl sulfate (NaDS), and water. Tested compositions ranged from 90 to 50 wt% water and had a cat-HECDS to NaDS wt% ratio of 2:1, 1:1, or 1:2, mimicking the in vivo hydration range and relative excess surfactant content expected from commercial rinse-off formulations. Steady-state flux of the model compound from each coacervate composition was found to vary with water content of the composition. When flux was plotted versus [(cat-HECDS:NaDS) × (1 - weight fraction water)]-1, a strong linear correlation (R2= 0.89) emerged. The in vitro release testing method proved capable of discriminating between clinically relevant differences in transport kinetics from different coacervate formulations using a practical sample size.
authors.affiliation: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, Ohio 45267.
authors.forename: Nada H
authors.initials: NH
authors.lastname: Baalbaki
authors.affiliation: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, Ohio 45267. Electronic address: gerald.kasting@uc.edu.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Kasting
mesh_terms: D000287:Administration, Topical; D002412:Cations / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D007701:Kinetin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010539:Permeability; D012629:Sebum / Q000378:metabolism*; D012869:Skin Absorption; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
chemical_list: D002412:Cations; D004337:Drug Carriers; D012967:Sodium Dodecyl Sulfate; D002482:Cellulose; C002283:hydroxyethylcellulose; C028913:dodecyl sulfate; D007701:Kinetin
keywords: bioavailability; coacervation; controlled release; permeability; polymeric drugs; site-specific delivery; skin