Evaluation of a dynamic dissolution/permeation model: Mutual influence of dissolution and barrier-flux under non-steady state conditions

[Display omitted] 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 changin...

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Bibliographic Details
Published in:International journal of pharmaceutics 2017-04, Vol.522 (1-2), p.50-57
Main Authors: Sironi, Daniel, Christensen, Mette, Rosenberg, Jörg, Bauer-Brandl, Annette, Brandl, Martin
Format: Article
Language:English
Subjects:
Algorithms
Apparent permeability
Chemistry, Pharmaceutical
Delayed-Action Preparations
Dissolution/permeation
Drug Compounding
Flux
Hydrocortisone
Hydrocortisone - administration & dosage
Hydrocortisone - chemistry
Membranes, Artificial
Models, Theoretical
Non-steady state
Permeability
Permeapad
Solubility
Suspensions
Tablets
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Summary:[Display omitted] 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2017.03.002