BMS 123 · Common Core (Tronc commun)Section 1.3 · Pharmacokinetics and drug absorption
Section 3 of 27
What controls absorption: the drug and its form
Explain how particle size, water solubility, the lipid–water partition coefficient, ionisation and concentration decide whether a drug is absorbed, and how the dosage form adds disintegration, dissolution and interactions.
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Why this matters
Two products can contain exactly the same amount of the same drug and still behave differently, because absorption depends on the physical and chemical form as much as on the molecule. This is where a pharmacist sees pharmacology in daily practice: a suspension is not a tablet, a tablet taken with milk is not the same as one taken with water, and a weak acid behaves differently in the stomach and in the intestine. Understanding these factors explains most of the surprises learners meet when a medicine disappoints.
What you need to know first
You need the idea from Unit 1.2 that a lipophilic, uncharged molecule crosses a membrane easily while a charged one does not, and the everyday meanings of acid, base and pH.
Words to know (5)
Particle size
The physical size of the drug particles: the smaller they are, the greater the surface exposed to fluid and the easier the absorption. A finely milled powder dissolves faster than the same weight of coarse granules.
Partition coefficient (P, log P)
A number describing how a drug distributes between a fat-like phase and a water phase; a high P means the drug prefers fat. A drug with a high log P diffuses through the lipid core of the membrane quickly.
pKa
The pH at which half of the drug molecules are ionised and half are not, so it predicts the charge at any given body pH. A weak acid with a low pKa is largely uncharged in the acidic stomach.
Disintegration and dissolution
Disintegration is the breaking up of a solid dosage form into particles; dissolution is the dissolving of those particles into the fluid. A tablet that never disintegrates cannot dissolve and therefore cannot be absorbed.
Excipient
An inactive substance added to a medicine to give it form, stability or taste, which can nevertheless change absorption. A lubricant or a binder in a tablet can slow the release of the active ingredient.
One idea at a timeIdea 1 / 6
In one sentence Small particles and good water solubility make a drug easier to absorb, because the drug must first dissolve in the body fluids.
Particle size and water solubility set the starting point
The size or mass of the drug molecules affects their permeability, and small molecules are easily absorbed. Water solubility matters for the same reason: the body is made largely of water, so a drug that dissolves readily can be presented to the membrane as a solution. Certain drugs do not dissolve into small enough particles to ensure rapid absorption. This is why liquids are absorbed better than solids and crystalloids are absorbed better than colloids: a solution is already dissolved, while a solid must be broken down and dissolved first. Particle size works together with solubility, because reducing the size of a poorly soluble drug exposes more surface to the fluid and speeds that dissolving step.
For example
A drug given as an oral solution is available for absorption almost at once, while the same drug compressed into a hard tablet must first break up and dissolve.
Pause and check yourself
Why are liquids generally absorbed better than solid dosage forms?
Show the answer
Because a liquid is already dissolved, while a solid must first disintegrate into particles and then dissolve in the fluid before it can cross the membrane.
Read detailed explanations
The pH–ionisation trade-off in numbers
The fraction of a drug that is unionised at a given pH is set by the distance between that pH and the drug’s pKa. When the pH equals the pKa, half the molecules are ionised and half are not. As the pH moves away from the pKa in the direction that favours the uncharged form, that fraction grows quickly. Consider a weak acid with a pKa of 4 placed in the stomach at pH 2. The pH is two units below the pKa, so most of the drug is unionised, lipophilic and able to diffuse. The same drug in the small intestine at pH 7 is three units above its pKa, so most of it is ionised, water-soluble and largely unable to cross. A weak base behaves in mirror image: a pKa of 8 makes it largely unionised in the intestine at pH 7 and largely ionised in the stomach at pH 2. Two practical lessons follow. First, do not ask only whether a drug is acidic or basic; ask where its pKa sits relative to the pH of each compartment. Second, because the small intestine has an enormous surface and a long transit time, a drug that is unionised there will usually be absorbed well even if the stomach was unfavourable.
Disintegration, dissolution and why the formulation is the first variable
For a solid oral dosage form the drug is not available for absorption when the tablet is swallowed; it becomes available only after two physical events. Disintegration breaks the tablet or capsule into granules and particles, usually within minutes in the gastric fluid. Dissolution then brings the individual drug molecules into solution, and only dissolved molecules can cross the gastrointestinal membrane. These two steps are the first rate-limiting events of oral absorption, and they are why the same chemical can behave like two different medicines. A tablet compressed too hard, a capsule with a coating that resists gastric fluid, a granule held together by a strong binder, or a powder with a very low water solubility can all delay or reduce the amount of drug that ever reaches solution. Excipients such as lubricants, binders, dispersing agents and starches influence these steps, and manufacturing differences between two batches of the same product can change them again. This is the practical link between pharmaceutics and pharmacokinetics: the formulation sets the starting concentration that every later ADME process will work from.
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Drug factors that change absorption
Six properties of the drug molecule and its form that decide how much of it dissolves and crosses the absorbing membrane.
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01 / 5Particle size
If the drawing is wider than this panel, scroll it sideways. Labels stay readable; the numbered explanations below show the same ideas.
Particle size
The physical size of the drug particles. Smaller particles expose more surface to the gut fluid, dissolve faster and are therefore absorbed faster; a coarse powder may dissolve too slowly for rapid absorption.
Concept map, not to scale. The six factors act together: a small, lipophilic, unionised molecule is ideal for diffusion, but a formulation or a food can still prevent it from dissolving.
Key points to remember
✓Small particles and good water solubility make dissolution easier, and dissolution must precede absorption.
✓A high lipid–water partition coefficient means the drug prefers fat and crosses the membrane quickly.
✓Only the unionised form of a weak acid or base crosses by simple diffusion, so pH decides how much is absorbed where.
✓A higher drug concentration at the absorbing surface gives a steeper gradient and more absorption.
✓Chemical instability — acid or enzymes — can destroy a drug before it ever reaches the membrane.
✓Solid forms must disintegrate then dissolve; excipients and interactions such as tetracycline with calcium can change everything.
Go deeper
Worked example
Predicting absorption for a weak acid, a weak base and a chelated antibiotic. Three situations are given: (A) a weak acidic drug swallowed on an empty stomach, (B) the same kind of weak basic drug swallowed at the same time, and (C) a tetracycline antibiotic swallowed with milk. Predict what happens to absorption in each case.
Situation A: in the acidic stomach (pH 1–3) the weak acid is largely unionised, lipophilic and able to diffuse through the gastric membrane, so absorption begins early.
Situation B: the weak base is largely ionised in the acidic stomach and therefore poorly absorbed there; it becomes unionised as it reaches the alkaline small intestine (pH 6–8) and is absorbed well instead.
Situation C: the calcium ions in the milk form an insoluble complex with the tetracycline, so even though the tablet may dissolve, the drug can no longer cross the membrane.
Comparison: solubility and lipid preference decide the route in A and B, while a chemical interaction in the gut removes the drug from solution altogether in C.
Absorption is decided by the drug molecule, by the pH of the fluid it meets and by everything else present in that fluid. Changing the fluid — with food, milk or an antacid — can change the outcome as much as changing the drug.
Common misconception
Beginners often believe that a weak acid is always absorbed in the stomach and a weak base never is. In reality absorption depends on the fraction that is unionised at the local pH and on how long the drug stays there; most absorption happens in the small intestine, which has far more surface area.
Check your reasoning
A patient complains that a medicine works well when taken with water but seems weaker when taken with breakfast. Using at least two factors from this section and one from Unit 1.4, explain how the meal could change the amount absorbed.
Reveal an answer
First, the concentration factor: a meal dilutes the dose and raises the volume in the stomach, so the gradient at the absorbing surface is smaller. Second, the dosage-form factor: food can coat the particles and slow disintegration and dissolution, delaying the release of the active ingredient. Third, the physiological factor from Unit 1.4: a high-fat meal slows gastric emptying, so the drug arrives later at the small intestine, where most absorption actually happens. The result is a lower and later peak rather than a different molecule.
Where this comes from
BMS 123 General Pharmacology II lecture notes — Part 1, Principles of Pharmacokinetics · Factors affecting drug absorption: physico-chemical properties, concentration, chemical instability, formulation and interactions
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About this course and its sources
Bilingual lessons organised from the supplied BMS 123 General Pharmacology II lecture notes (Principles of Pharmacokinetics and Principles of Pharmacodynamics). Diagrams are original educational schematics; pharmacology, nursing and French-language review are pending.