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

Abstract

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 (Kp') to in vivo clinical permeation constants (kp), 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, Kp'from D-HFM system was compared to (kp) from literature, as well as Kp' 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%). Kp' from D-HFM system was also closer to in vivo kp; the two other in vitro models showed lower Kp'. Overall, studies reflect that HFM module has potential to incorporate drug permeation into the in vitro assessment of in vivo tablet and capsule performance.