Developability assessment of clinical drug products with maximum absorbable doses.

Maximum absorbable dose refers to the maximum amount of an orally administered drug that can be absorbed in the gastrointestinal tract. Maximum absorbable dose, or D(abs), has proved to be an important parameter for quantifying the absorption potential of drug candidates. The purpose of this work is to validate the use of D(abs) in a developability assessment context, and to establish appropriate protocol and interpretation criteria for this application.

A general approach to the apparent permeability index.

The apparent permeability index is widely used as part of a general screening process to study drug absorption, and is routinely obtained from in vitro or ex vivo experiments. A classical example, widely used in the pharmaceutical industry, is the in vitro Caco-2 cell culture model. The index is defined as the initial flux of compound through the membrane (normalized by membrane surface area and donor concentration) and is typically computed by adapting a straight line to the initial portion of the recorded amounts in the receiver compartment, possibly disregarding the first few points when lagging of the transfer process through the membrane is evident.

Helodermin-loaded nanoparticles: characterization and transport across an in vitro model of the follicle-associated epithelium.

M cells represent a potential portal for oral delivery of peptides and proteins due to their high endocytosis abilities. An in vitro model of human FAE (co-cultures) was used to evaluate the influence of M cells on the transport of free and encapsulated helodermin--a model peptide--across the intestinal epithelium. M cells enhanced transport of intact helodermin (18-fold, Papp=3 x 10(-6) cm s(-1)).

Inhibitory effect of fruit extracts on P-glycoprotein-related efflux carriers: an in-vitro screening.

In this study, standardized food extracts were screened for their possible inhibitory effect on the P-glycoprotein (P-gp)-mediated efflux of 3H-ciclosporin A (CsA) using the in-vitro Caco-2 model. CsA is commonly used as a substrate for P-gp-related efflux carriers and is characterized by a polarity in transport, the absorptive transport being much lowerthan the secretorytransport (polarityfactor: PF approximately 7). Of the 68 tested, nine extracts showed a decreased efflux of CsA (< 75% of the reference value) and were retained for further experiments on the bidirectional transport of CsA across Caco-2 monolayers.