Dissolution-Hollow Fiber Membrane (D-HFM) System to Anticipate Biopharmaceutics Risk of Tablets and Capsules

Abstract

A dissolution-hollow fiber membrane (D-HFM) system with relatively high area/volume ratio was previously characterized and showed favorably high percent drug absorption. Also, it's in vitro permeation constant (Kp.Ç.) was close to in vivo human permeation constant (kp). The objective of the current study was to predict the in vivo human absorption profile and biopharmaceutic performance of five drug products using the D-HFM system. Four immediate-release (IR) and one extended-release (ER) solid oral dosage form were subjected to the D-HFM system. Tablets and capsule dissolution were also measured using USP apparatus II. Drug solutions were also subjected to D-HFM testing. Predicted and observed absorption profiles in D-HFM system showed close agreement for each solid oral dosage form. Levy-Polli plots from D-HFM system successfully predicted the four IR products to be low biopharmaceutic risk due to permeation rate limited or mixed dissolution/permeation rate limited absorption, and successfully predicted metoprolol ER product to be high biopharmaceutic risk due to dissolution rate limited absorption. These observations showed potential of the in vitro D-HFM system to be utilized in biopharmaceutics risk assessment of in vivo tablet and capsule performance.