pharmacokinetics and biopharmaceutic

What is pharmacokinetics

Pharmacokinetics is the study of what the body does to a drug, encompassing ADME: absorption, distribution, metabolism, and excretion

What is biopharmaceutics?

Biopharmaceutics examines how the physicochemical properties of APIs, dosage forms, and administration routes affect the rate and extent of drug action.

What must occur before an API in a solid oral dosage form can be absorbed?

The drug must disintegrate into particles and then dissolve in GIT fluids to become molecularly available for absorption

Why is it essential for an API to be in solution to be absorbed?

Only the dissolved (molecular) form of the API can cross biological membranes into the bloodstream.

Differentiate between solubility and dissolution rate.

• Solubility is the maximum amount of API that can dissolve in a solvent

• Dissolution rate is how quickly the API dissolves

How do suspension and solution formulations affect the absorption process

• Suspensions: Skip disintegration, allowing faster dissolution.

• Solutions: Skip both disintegration and dissolution, offering the fastest onset of action.

bioavailability

The fraction of an administered dose that reaches the systemic circulation unchanged

What factors influence oral bioavailability?

• Extent of absorption

• First-pass metabolism in the liver

Why must dosing be adjusted when switching drug formulations?

Different formulations may have different bioavailability, impacting drug exposure.

What are the three main anatomical sites in the GIT where drug absorption can occur?

• Stomach

• Small intestine (primary site)

• Large intestine

Why is the small intestine the major site of absorption for small molecule drugs?

• large SA

• good blood supply

• plenty of fluid

What are the three main mechanisms by which drugs cross the GIT membrane?

• Passive diffusion

• Facilitated diffusion

• Active transport

What drives passive diffusion of an API across the GIT membrane?

A concentration gradient from the GIT to blood; maintained by systemic circulation

What two properties must an API have to be well absorbed via passive diffusion?

• Aqueous solubility – to dissolve in intestinal fluids

• Fat solubility (lipophilicity) – to cross the lipid membranes

What physicochemical properties of an API influence its GIT absorption?

• Aqueous solubility

• Log P

• pKa

What does Log P represent?

Log P measures how an API partitions between:

• Octanol (fat phase)

• Water (aqueous phase)

How do Log P values affect drug absorption?

• Log P < 0: Hydrophilic, favours water

• Log P = 0: Equal preference

• Log P > 0: Lipophilic, favours membrane passage

What does pKa measure in drug chemistry?

The pKa quantifies the strength of acidic or basic groups, i.e., how readily they give up (or hold onto) a proton (H⁺)

Why is pKa alone meaningless without context?

must specify whether it refers to an acid or a base because the pKa interpretation differs between them.

How do multiple pKa values influence drug ionization?

Each ionizable group has its own pKa. The most ionizable (strongest) group typically dominates the drug's ionization behavior.

Why do we assign pKa values to bases

When a base accepts a proton, it becomes a conjugate acid, which can lose the proton. This proton loss defines the conjugate acid's pKa

What does a high pKa value for a conjugate acid indicate about its base?

It means the base is strong—i.e., the conjugate acid holds the proton tightly and is reluctant to release it.

What happens when log P is too high or too low?

• Too high: Poor aqueous solubility → reduced absorption.

• Too low: Poor membrane permeability → limited absorption.

Why is the ionisation state of a drug important for absorption?

• Ionised forms are water-soluble but poorly absorbed.

• Unionised forms are lipid-soluble and can cross membranes easily.

What is the rule of thumb regarding pKa and ionisation?

At pH = pKa, the drug is 50% ionised and 50% unionised

Why is ibuprofen (pKa = 4.8) still well absorbed in the small intestine, despite being mostly ionised?

Due to dynamic equilibrium: unionised drug is absorbed, which pulls more ionised drug into unionised form, maintaining absorption.

What is Lipinski’s Rule of Five?

• ≤ 5 H-bond donors

• ≤ 10 H-bond acceptors

• MW < 500

• log P < 5