Characterization of Dissolution-Permeation System using Hollow Fiber Membrane Module and Utility to Predict in Vivo Drug Permeation Across BCS Classes

A dissolution-permeation system has potential to provide insight into the kinetic contributions of dissolution and permeation to overall drug absorption. The goals of the study were to characterize a dissolution-hollow fiber membrane (D-HFM) system and compare its resulting in vitro drug permeation...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2022-11, Vol.111 (11), p.3075-3087
Main Authors: Adhikari, Asmita, Seo, Paul R, Polli, James E
Format: Article
Language:English
Subjects:
Biopharmaceutics - methods
Caco-2 Cells
Humans
Intestinal Absorption
Permeability
Solubility
Tablets
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Summary:A dissolution-permeation system has potential to provide insight into the kinetic contributions of dissolution and permeation to overall drug absorption. The goals of the study were to characterize a dissolution-hollow fiber membrane (D-HFM) system and compare its resulting in vitro drug permeation constants (K ) to in vivo clinical permeation constants (k ), for four drugs in various Biopharmaceutics Classification System (BCS) classes. Model predictions for D-HFM were made based on derived mixing tank (MT) and complete radial (CRM) flow models and independent measurement of membrane permeability. Experimental D-HFM studies included donor flow rate and donor volume sensitivity studies, and drug permeation profile studies. Additionally, for the four drugs, K from D-HFM system was compared to (k ) from literature, as well as K values from side-by-side diffusion cell and dissolution/Caco-2 system. Results show progressive D-HFM system development as a dissolution-permeation tool. Results indicated that D-HFM models using MT or CRM provided close agreement between predicted and observed drug permeation profiles. Drug permeation in D-HFM system was volume dependent, as predicted. Favorably, more drug permeated through the D-HFM system (10-20% in 60 min) compared to side-by-side diffusion cell (1%) and dissolution/Caco-2 system (0.1%). K from D-HFM system was also closer to in vivo k ; the two other in vitro models showed lower K . Overall, studies reflect that HFM module has potential to incorporate drug permeation into the in vitro assessment of in vivo tablet and capsule performance.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2022.07.002