Thus, low dose strengths of a drug could meet the criterion for a biowaiver (see below), whereas higher dose strengths might still require human testing. The threshold for high solubility depends on the dose. That volume (250 mL) is approximately equal to 8 oz., based on the premise that a patient would take a pill with a glass of water. The highest dose strength of the drug must be soluble in 250 mL or less of aqueous medium at all pH values between 1 and 7.5, inclusive. time curve in plasma, urine, and/or feces for the parent compound and metabolites in order to account for everything that was absorbed and subsequently retained, cleared, and/or metabolized. Alternatively, one can demonstrate in humans, using a suitably powered statistical design, that at least 90% of a drug is absorbed after oral administration, which is not a simple matter, due to intrinsic variability between subjects and the need to quantify the area under the concentration vs. Note that this is a relative, not absolute, definition of high permeability.

The permeability model must be able to clearly distinguish high-permeability and low-permeability compounds. In a validated in vitro permeability model, a test API must be more permeable than a co-dosed drug whose in vivo human fraction absorbed is known to be at least 90%. Testing specifications were established for “high” permeability and “high” solubility characteristics of the raw API, namely: Food and Drug Administration (FDA) embarked on a bold initiative and went out on a limb by issuing a regulatory guidance on the BCS, 2 thereby making it part of the drug approval process. This is the basic premise underlying the Biopharmaceutics Classification System (BCS). In layman’s terms, three benchtop experiments using petri dishes, dissolution baths, test tubes, and beakers can eliminate the need for human testing. 1 The beauty of the system is that it is all performed using in vitro test systems. Thus -and this is the radical part -one ought to be able to accurately determine, from two intrinsic properties of the API (permeability and solubility) and one property of the drug product (dissolution rate), a human outcome. For well-behaved (highly permeable and highly soluble) drugs, assuming that the dose form dissolves rapidly (i.e., the drug product is an immediate-release formulation), the fraction absorbed (the amount of drug that actually makes it across the gut wall) should be consistent regardless of the composition of the formulated product.

In the late 1980s and early 1990s, a small group of influential and forward-thinking pharmaceutical scientists posited a somewhat radical hypothesis: the extent of absorption of an orally administered drug can be predicted by knowing 1) the intrinsic permeability of the active pharmaceutical ingredient (API) across the intestinal mucosa and 2) the concentration of the drug at the site of absorption.

Bcs class 4 drugs