title: Application of confocal laser scanning microscopy in characterization of chemical enhancers in drug-in-adhesive transdermal patches.
abstract: The purpose of this study was to evaluate the application of confocal laser scanning microscopy (CLSM) in the examination of the embedment and the release characteristics of chemical permeation enhancers from transdermal drug delivery systems (TDDSs) of the "drug-in-adhesive" type. The enhancer lauric acid and a lauric acid fluorescing probe of the Bodipy type were incorporated into TDDSs consisting of an acrylic, a polyisobutylene, or a silicone polymer adhesive. Three-dimensional confocal images of the distribution were obtained before and during release into an aqueous medium. The images showed that the lauric acid fluorescing probe was homogeneously embedded in all the adhesives except for 1 polyisobutylene. The release profiles and release rate constants of the lauric acid fluorescing probe were consistent with data from a release study of lauric acid performed using conventional measurements of the released amounts. This indicated that lauric acid was distributed in a homogeneous manner. Furthermore, it was possible to illustrate the mechanics of the diffusion process inside the TDDS and compare these patterns with theoretically drawn profiles, based on Fick's law of diffusion. CLSM was demonstrated to be an excellent tool to study how enhancers are incorporated and diffuse into a TDDS.
authors.affiliation: Department of Pharmaceutical Research, Pharmacia and Upjohn Hillerod AS, Hillerod, Denmark. michael@qvist.net
authors.forename: Michael H
authors.initials: MH
authors.lastname: Qvist
authors.forename: Ulla
authors.initials: U
authors.lastname: Hoeck
authors.forename: Bo
authors.initials: B
authors.lastname: Kreilgaard
authors.forename: Flemming
authors.initials: F
authors.lastname: Madsen
authors.forename: Lars
authors.initials: L
authors.lastname: Hovgaard
authors.forename: Sven
authors.initials: S
authors.lastname: Frokjaer
mesh_terms: D000269:Adhesives / Q000737:chemistry*; D000279:Administration, Cutaneous; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D018613:Microscopy, Confocal / Q000379:methods*; D008956:Models, Chemical
chemical_list: D000269:Adhesives; D005079:Excipients