Biopharmaceutics and Formulation Development - Bioavailability and Methods

Critical terminology and concepts regarding bioavailability, bioequivalence, and assessment methods including in vitro, in vivo, ex vivo, and in silico techniques.

Bioavailability

The rate and fraction of the initial dose of a drug that successfully reaches either the site of action or the bodily fluid domain from which the drug's intended targets have unimpeded access.

Absolute availability

The systemic availability of a drug administered orally (or extravascularly) determined by a comparison with intravenous (IV) administration.

Relative availability

The systemic availability of a drug administered orally determined by comparison with an oral standard of the same drug.

3R principle

Defined by Russell and Burch in 1959, this rule stands for Replace, Reduce, and Refine to set principles for ethical animal use in research.

In vitro models

Assessment methods using simulated gastrointestinal digestion, artificial membranes, or Caco-2 cell cultures.

Ex vivo models

Techniques utilizing isolated or reconstituted cell membranes, Ussing chambers, or gastrointestinal organs in laboratory conditions.

In situ models

Assessment methods involving intestinal perfusion in animals.

In silico models

Mathematical models and computer simulations used to predict a drug's bioavailability based on its chemical structure and physical properties.

Sink condition

The ability of the dissolution media to dissolve at least 3 times the amount of drug that is in the dosage form.

Noyes-Whitney equation

An equation where the Dissolution Rate ($R$) is shown to be proportional to the difference between saturation concentration ($Cs$) and API concentration at time t ($Ct$).

First-pass metabolism

A type of presystemic metabolism that occurs when an absorbed drug passes directly through the liver before reaching systemic circulation.

Cmax

The peak plasma concentration that provides an indication of whether the drug is sufficiently absorbed to provide a therapeutic response.

Tmax

The peak time which indicates the rate of absorption; it decreases as the rate of absorption increases.

AUC (Area Under the Curve)

The area under the plasma level-time curve that measures the extent of absorption or total amount of drug reaching systemic circulation.

$$X^{\infty}_{u}$$

The cumulative amount of drug excreted in the urine, which is related to the AUC and increases as the extent of absorption increases.

Acute pharmacological response method

A pharmacodynamic method used when pharmacokinetic measurements are difficult, involving effects like EEG reading, ECG, and pupil diameter.

Steady state

A condition in multiple-dose studies reached after administering a drug for 5 to 6 elimination half-lives.

Ussing chamber

The gold standard ex vivo method used to study transepithelial drug transport and regional differences in intestinal absorption.

Franz Diffusion Cell

A methodology utilized to assess skin permeability and provide insights into the relationships between skin, drug, and formulation.

PDMS (Polymethylsiloxane)

An example of a hydrophobic synthetic membrane often employed to simulate the skin in Franz cell drug diffusion studies.