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Mechanistic analysis of solute transport in an in vitro physiological two‐phase dissolution apparatus
Author(s) -
Mudie Deanna M.,
Shi Yi,
Ping Haili,
Gao Ping,
Amidon Gordon L.,
Amidon Gregory E.
Publication year - 2012
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1803
Subject(s) - dissolution , solubility , kinetics , aqueous solution , phase (matter) , chemistry , absorption (acoustics) , diffusion , dissolution testing , aqueous two phase system , chromatography , thermodynamics , materials science , organic chemistry , biopharmaceutics classification system , physics , quantum mechanics , composite material
In vitro dissolution methodologies that adequately capture the oral bioperformance of solid dosage forms are critical tools needed to aid formulation development. Such methodologies must encompass important physiological parameters and be designed with drug properties in mind. Two‐phase dissolution apparatuses, which contain an aqueous phase in which the drug dissolves (representing the dissolution/solubility component) and an organic phase into which the drug partitions (representing the absorption component), have the potential to provide meaningful predictions of in vivo oral bioperformance for some BCS II, and possibly some BCS IV drug products. Before such an apparatus can be evaluated properly, it is important to understand the kinetics of drug substance partitioning from the aqueous to the organic medium. A mass transport analysis was performed of the kinetics of partitioning of drug substance solutions from the aqueous to the organic phase of a two‐phase dissolution apparatus. Major assumptions include pseudo‐steady‐state conditions, a dilute aqueous solution and diffusion‐controlled transport. Input parameters can be measured or estimated a priori . This paper presents the theory and derivation of our analysis, compares it with a recent kinetic approach, and demonstrates its effectiveness in predicting in vitro partitioning profiles of three BCS II weak acids in four different in vitro two‐phase dissolution apparatuses. Very importantly, the paper discusses how a two‐phase apparatus can be scaled to reflect in vivo absorption kinetics and for which drug substances the two‐phase dissolution systems may be appropriate tools for measuring oral bioperformance. Copyright © 2012 John Wiley & Sons, Ltd.