Chemistry • Year 12 • Module 8 • Lesson 14
Solubility, Polarity & Drug Delivery
Lock in the vocabulary of drug solubility, log P, Lipinski's Rule of Five, delivery routes, prodrugs and controlled-release formulations before tackling data and extended-response questions.
1. Term–definition match
Ten definitions are listed below in shuffled order. Write the matching term from this list in the right-hand column: like dissolves like, partition coefficient (log P), prodrug, first-pass metabolism, bioavailability, enteric coating, transdermal patch, liposome, lipophilicity, controlled-release formulation. 10 marks
| # | Definition | Matching term |
|---|---|---|
| 1.1 | The guiding principle that polar solutes dissolve readily in polar solvents and non-polar solutes dissolve in non-polar solvents. | |
| 1.2 | The logarithm of the ratio of drug concentration in octanol to drug concentration in water at equilibrium; predicts how readily a drug crosses lipid membranes. | |
| 1.3 | An inactive or less active compound that is converted inside the body by metabolism into the active drug. | |
| 1.4 | Metabolism of an orally administered drug in the gut wall and liver before it reaches general systemic circulation, reducing the effective dose. | |
| 1.5 | The fraction of an administered drug dose that reaches the systemic circulation unchanged and is available to exert its effect. | |
| 1.6 | A polymer coating applied to a tablet that resists dissolution in the acidic stomach but dissolves in the alkaline small intestine, protecting the drug or the stomach. | |
| 1.7 | A medicated adhesive patch placed on skin to deliver a drug slowly into the bloodstream, bypassing the digestive tract and first-pass metabolism. | |
| 1.8 | A spherical phospholipid bilayer vesicle that can encapsulate both water-soluble and lipid-soluble drugs for targeted delivery. | |
| 1.9 | The tendency of a molecule to dissolve in fats, oils and lipid environments rather than water; linked to non-polar character. | |
| 1.10 | A drug formulation designed to release the active ingredient gradually over an extended period, maintaining a more stable therapeutic concentration. |
2. True or false — with correction
Circle T or F for each statement. If false, write the corrected version on the line below. 10 marks (1 T/F, 1 correction where needed)
2.1 A highly polar drug with many –OH groups will generally dissolve more readily in aqueous blood plasma than in lipid cell membranes. T / F
2.2 Lipinski’s Rule of Five states that a drug with molecular mass > 500 Da is likely to have good oral bioavailability. T / F
2.3 A prodrug is inactive or less active when administered and is converted into the active compound by metabolism inside the body. T / F
2.4 First-pass metabolism increases the oral bioavailability of a drug by activating it in the liver before it reaches general circulation. T / F
2.5 A transdermal patch can be a preferred delivery route for drugs that are significantly degraded by first-pass metabolism when swallowed. T / F
3. Cloze passage — fill the blanks
Choose from the word bank to complete the paragraph. Use each word once only. 8 marks
Word bank: polar • non-polar • log P • lipophilic • prodrug • first-pass • enteric • intravenous
The principle “like dissolves like” explains why drugs dissolve more readily in aqueous body fluids, while drugs interact more effectively with lipid cell membranes. The partition coefficient measures how a drug is: a high positive value indicates strong preference for lipid over water. A drug that is administered in an inactive form and is converted to the active compound by metabolism inside the body is called a . Oral tablets can suffer from metabolism, which reduces the fraction of active drug reaching general circulation. To protect a drug from stomach acid, an coating can be applied to the tablet. For the fastest possible delivery of a high concentration of drug, administration bypasses the gut and delivers the drug directly into the bloodstream.
4. Function recall
Answer each in 1–2 sentences using precise chemical terms. 8 marks (2 each)
4.1 What is the chemical basis of the “like dissolves like” rule, and why does it matter for drug formulation?
4.2 What function does the partition coefficient (log P) serve in medicinal chemistry?
4.3 Why is first-pass metabolism a problem for some orally administered drugs?
4.4 What is the purpose of a controlled-release formulation, and how does its chemistry achieve that purpose?
5. Build a concept map
Draw labelled arrows between the six terms below to show how they connect. Each arrow must carry a linking phrase (e.g. “determines”, “reduces”, “is a strategy to avoid”). Aim for at least 6 labelled arrows. 6 marks
Supplied terms: polarity • aqueous solubility • lipophilicity (log P) • membrane permeability • oral bioavailability • delivery route.
Q1 — Term–definition matches
1.1 like dissolves like • 1.2 partition coefficient (log P) • 1.3 prodrug • 1.4 first-pass metabolism • 1.5 bioavailability • 1.6 enteric coating • 1.7 transdermal patch • 1.8 liposome • 1.9 lipophilicity • 1.10 controlled-release formulation.
Q2 — True / false with correction
2.1 True. Polar drugs interact through hydrogen bonding and dipole forces with water molecules in plasma.
2.2 False. Correction: Lipinski’s Rule of Five states that molecular mass should be less than 500 Da for good oral bioavailability; a drug exceeding 500 Da is likely to be poorly absorbed orally.
2.3 True.
2.4 False. Correction: First-pass metabolism reduces oral bioavailability by breaking down or chemically modifying the drug in the gut wall and liver before it reaches systemic circulation; less active drug reaches the rest of the body.
2.5 True. A transdermal patch delivers drug through the skin directly into the bloodstream, avoiding the digestive tract and the hepatic portal system, and thereby bypassing first-pass metabolism.
Q3 — Cloze passage
In order: polar • non-polar • log P • lipophilic • prodrug • first-pass • enteric • intravenous.
Q4 — Function recall
4.1 Polarity arises from unequal electron distribution in bonds. Polar molecules interact via hydrogen bonds and dipole–dipole forces with water, so they dissolve well in it; non-polar molecules interact mainly via dispersion forces and dissolve better in lipid environments. Formulating a drug requires matching these properties to the body fluids and barriers it must cross.
4.2 Log P quantifies the relative affinity of a drug for lipid (octanol) versus aqueous environments. A high log P means the drug is more lipophilic and better able to cross lipid bilayer membranes; a low log P means it is more hydrophilic and may dissolve well in plasma but cross membranes poorly.
4.3 When a drug is swallowed it is absorbed from the gut and carried via the hepatic portal vein to the liver before reaching general circulation. The liver metabolises a portion of the drug—sometimes converting it to an inactive form—so less active drug reaches the rest of the body. This reduces oral bioavailability and means a larger oral dose may be needed compared with a non-oral route.
4.4 A controlled-release formulation delivers the active drug gradually over an extended period, maintaining a more stable therapeutic concentration rather than a rapid spike followed by a rapid fall. This is achieved chemically through coatings, polymer matrices or diffusion barriers that slow dissolution or diffusion of the drug into surrounding fluid.
Q5 — Sample concept map
Valid arrows include: polarity → determines → aqueous solubility; polarity → inversely related to → lipophilicity (log P); lipophilicity (log P) → determines → membrane permeability; aqueous solubility → contributes to → oral bioavailability; membrane permeability → contributes to → oral bioavailability; oral bioavailability → guides selection of → delivery route. Award 1 mark per correctly directed, labelled arrow (max 6).