title: Evaluation of drug release from gels on pig nasal mucosa in a horizontal Ussing chamber.
abstract: In this study, controlled release gel formulations containing dihydroalprenolol (DHA), hydrocortisone (HC) or testosterone (TS) in Carbopol 934P (C934) were evaluated using pig nasal mucosa in a horizontal Ussing chamber. The controlled release gel formulations were designed by including DHA in vesicle bilayers formed with sodium dodecyl sulphate (SDS) (1.4 and 36 mM) and by partitioning TS to the core of Brij 58 (B58, 1%) micelles. For comparison, unmodified gels and solutions of the drugs and additives were examined in parallel experiments. The viability and toxicity were evaluated with electrophysiological measurements and light microscopy. The results showed that C934 did not affect the viability of the mucosa and that the rate and profile of the appearance on the receiver side was independent of whether the substances were released from an unmodified gel or an unmodified solution. Continuous electrophysiological measurements made during exposure showed that B58 (1%) and SDS (1.4 mM) inactivated the mucosa, whereas SDS (36 mM) activated it. Investigations made after a 90-min exposure to the formulations showed that all the modified gels had inactivated the mucosa and had negative effects on the morphology. For the TS-B58 (1%) and the DHA-SDS (36 mM) gels, the rate-limiting step in transport was the release from the formulation. The results confirmed that gels from C934 are suitable for nasal administration and also clearly indicated the different degrees of toxicity of the controlled release formulations evaluated in this study. The horizontal Ussing chamber method was a suitable tool for the evaluation of gels for nasal administration.
authors.affiliation: Department of Pharmacy, Uppsala University, Box 580, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Osth
authors.forename: Mattias
authors.initials: M
authors.lastname: Paulsson
authors.forename: Erik
authors.initials: E
authors.lastname: Björk
authors.forename: Katarina
authors.initials: K
authors.lastname: Edsman
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002626:Chemistry, Pharmaceutical; D015194:Diffusion Chambers, Culture / Q000295:instrumentation / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005782:Gels / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000378:metabolism*; D013552:Swine
chemical_list: D005782:Gels