IVIVC Revised

Purpose To revise the IVIVC considering the physiologically sound Finite Absorption Time (F.A.T.) and Finite Dissolution Time (F.D.T.) concepts. Methods The estimates τ and τ d for F.A.T. and F.D.T., respectively are constrained by the inequality τ d  ≤  τ ; their relative magnitude is dependent on...

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Bibliographic Details
Published in:Pharmaceutical research 2024-02, Vol.41 (2), p.235-246
Main Authors: Alimpertis, Nikolaos, Simitopoulos, Antony, Tsekouras, Athanasios A., Macheras, Panos
Format: Article
Language:English
Subjects:
Biochemistry
Biological Availability
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Carbamazepine
Child
Dissolution
Drug dosages
Drug Liberation
Estimates
Football (College)
Humans
Inequality
Medical Law
Original Research Article
Pharmaceuticals
Pharmacokinetics
Pharmacology/Toxicology
Pharmacy
Physiological aspects
Solubility
Theophylline
Therapeutic Equivalency
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Summary:Purpose To revise the IVIVC considering the physiologically sound Finite Absorption Time (F.A.T.) and Finite Dissolution Time (F.D.T.) concepts. Methods The estimates τ and τ d for F.A.T. and F.D.T., respectively are constrained by the inequality τ d  ≤  τ ; their relative magnitude is dependent on drug’s BCS classification. A modified Levy plot, which includes the time estimates for τ and τ d was developed. IVIVC were also considered in the light of τ and τ d estimates. The modified Levy plot of theophylline, a class I drug, coupled with the rapid (30 min) and very rapid (15 min) dissolution time limits showed that drug dissolution/absorption of Class I drugs takes place in less than an hour. We reanalyzed a carbamazepine (Tegretol) bioequivalence study using PBFTPK models to reveal its complex absorption kinetics with two or three stages. Results The modified Levy plot unveiled the short time span (~ 2 h) of the in vitro dissolution data in comparison with the duration of in vivo dissolution/absorption processes (~ 17 h). Similar results were observed with the modified IVIVC plots. Analysis of another set of carbamazepine data, using PBFTPK models, confirmed a three stages absorption process. Analysis of steady-state (Tegretol) data from a paediatric study using PBFTPK models, revealed a single input stage of duration 3.3 h. The corresponding modified Levy and IVIVC plots were found to be nonlinear. Conclusions The consideration of Levy plots and IVIVC in the light of the F.A.T. and F.D.T. concepts allows a better physiological insight of the in vitro and in vivo drug dissolution/absorption processes.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-024-03653-x