Biorelevant medium is a medium that has some relevance to the in vivo performance of the dosage unit. Choice of a biorelevant medium is based on:
(1) a mechanistic approach that considers the absorption site, if known, and
(2) whether the rate-limiting step to absorption is the dissolution or permeability of the compound.
In some cases, the biorelevant medium will be different from the test conditions chosen for the regulatory test, and the time points are also likely to be different. If the compound dissolves quickly in the stomach and is highly permeable, gastric emptying time may be the rate-limiting step to absorption. In this case, the dissolution test should demonstrate that the drug is released quickly under typical gastric (acidic) conditions.
On the other hand, if dissolution occurs primarily in the intestinal tract (e.g., for a poorly soluble, weak acid), a higher pH range (e.g., simulated intestinal fluid with a pH of 6.8) may be more appropriate. The fed and fasted states may also have significant effects on the absorption or solubility of a compound.
Compositions of media that simulate the fed and fasted states can be found in the literature. These media reflect changes in pH, bile concentrations, and osmolarity after meal intake and therefore have a composition different from that of typical compendial media. They are primarily used to establish in vitro–in vivo correlations during formulation development and to assess potential food effects and are not intended for quality control purposes.
For quality control purposes, the substitution of natural surfactants (bile components) with appropriate synthetic surfactants is permitted and encouraged because of the expense of the natural substances and the labor-intensive preparation of the biorelevant media.
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Reference: USP Chapter <1092>
