Biopharmaceutics and pH-Partition Theory

Flashcards covering the vocabulary and core principles of the pH-partition theory, including the roles of pKa, pH, and ionization in drug absorption.

pH-Partition Theory

A theory proposed by Brodie et al. stating that drug transfer and absorption across membranes are influenced by the drug's $pKa$ and the $pH$ of the gastrointestinal tract and blood stream.

pKa

The $pH$ value at which exactly $50\%$ of a drug is in its ionized form.

Non-ionized form

The uncharged form of a drug which is more lipid-soluble and can efficiently cross lipid membranes by passive diffusion.

Ionized form

The charged form of a drug that is unable to efficiently pass through the lipid membrane.

D value

A ratio determined experimentally or calculated theoretically to represent the total concentration gradient across a membrane; a larger value indicates a faster expected absorption rate.

Equilibrium (pH-Partition Hypothesis)

The state reached when the concentration of the non-ionized form of a drug is equal on both sides of a membrane, even if total concentrations differ.

Passive diffusion

The movement of the non-ionized form of a drug across the lipid material of the membrane barrier.

Weak Acid [U]/[I] Ratio

The mathematical relationship used to determine the ratio of uncharged to ionized molecules, calculated as $10^{pKa - pH}$.

Brodie et al. (Shore, et al. 1957)

The researchers who proposed the pH-partition theory and tested it by perfusing the stomach or intestine of rats in situ.

Solubility-Diffusion Model

Another name for the pH-Partition Theory describing the necessity for a drug to be soluble in both lipid and aqueous phases to cross membrane barriers.

fu (Fraction non-ionized)

The fraction of a drug that is in its uncharged state, which can be modified by changing the $pH$ of the GI tract to influence the rate of absorption.