title: Evaluation of a dynamic dissolution/permeation model: Mutual influence of dissolution and barrier-flux under non-steady state conditions.
abstract: Combined dissolution/permeation testing is gaining increasing attention as an in vitro tool for predictive performance ranking of enabling oral formulations. The current aim was to study how in vitro drug permeation evolves under conditions, where the donor concentration is changing (non-steady state). To this end, a model case was construed: compacts of pure crystalline hydrocortisone methanolate (HC·MeOH) of slow release rates were prepared, and their dissolution and permeation determined simultaneously in a side-by-side setup, separated by a biomimetic barrier (Permeapad®). This was compared to a corresponding setup for a suspension of micronized hydrocortisone (HC). The HC suspension showed constant dissolved HC concentration and constant flux across the barrier, representing the permeation-limited situation. For the HC·MeOH compacts, various dynamic scenarios were observed, where dissolution rate and flux influenced each other. Interestingly, for all the dynamic scenarios, the incremental flux values obtained correlated nicely with the corresponding actual donor concentrations. Furthermore, donor depletion was tested using a HC solution. The dynamic interplay between decrease in donor concentration (down to less than 10% of the initial concentration) and flux was studied. The experiences gained are discussed in terms of further developing combined dissolution/permeation setups.
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sironi
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Christensen
authors.affiliation: AbbVie GmbH & Co. KG, Knollstraße 50, D-67061 Ludwigshafen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Bauer-Brandl
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark. Electronic address: mmb@sdu.dk.
authors.forename: Martin
authors.initials: M
authors.lastname: Brandl
mesh_terms: D000465:Algorithms; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D006854:Hydrocortisone / Q000008:administration & dosage / Q000737:chemistry; D008567:Membranes, Artificial; D008962:Models, Theoretical; D010539:Permeability; D012995:Solubility; D013535:Suspensions; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D008567:Membranes, Artificial; D013535:Suspensions; D013607:Tablets; D006854:Hydrocortisone
keywords: Apparent permeability; Dissolution/permeation; Flux; Hydrocortisone; Hydrocortisone (PubChem CID: 5754); Non-steady state; Permeapad