Understanding the physicochemical properties of drug substances is essential for predicting drug behavior in biological systems. These properties influence solubility, permeability, stability, absorption, distribution, and overall pharmacokinetics. This quiz is aligned with Pharm.D. coursework, particularly from PHA5439 and PHA5176, and is designed to test your knowledge of drug design, formulation, and therapeutic performance.
1. Which of the following is a key physicochemical property affecting drug solubility?
- A. Partition coefficient
- B. pKa
- C. Molecular weight
- D. All of the above
Correct answer: D. All of the above
2. Lipophilicity of a drug is most commonly expressed as:
- A. pH
- B. Log P
- C. Ka
- D. pKa
Correct answer: B. Log P
3. Which functional group increases water solubility in a drug molecule?
- A. Ester
- B. Hydroxyl
- C. Alkyl
- D. Halogen
Correct answer: B. Hydroxyl
4. A drug with a high Log P value is likely to:
- A. Be poorly absorbed
- B. Have low lipophilicity
- C. Cross cell membranes easily
- D. Be rapidly excreted
Correct answer: C. Cross cell membranes easily
5. What does pKa of a drug indicate?
- A. Potency
- B. Rate of metabolism
- C. Acid dissociation constant
- D. Shelf-life
Correct answer: C. Acid dissociation constant
6. Which of the following factors most affects the ionization of a drug?
- A. Partition coefficient
- B. Environmental pH and pKa
- C. Temperature
- D. Surface area
Correct answer: B. Environmental pH and pKa
7. Which property primarily influences drug absorption across biological membranes?
- A. Melting point
- B. Color
- C. Lipophilicity
- D. Odor
Correct answer: C. Lipophilicity
8. According to the Henderson-Hasselbalch equation, weak acids are mostly ionized when:
- A. pH = pKa
- B. pH < pKa
- C. pH > pKa
- D. pH is neutral
Correct answer: C. pH > pKa
9. Which of the following drugs would most likely cross the blood-brain barrier?
- A. Hydrophilic and highly ionized
- B. Large molecular weight and hydrophilic
- C. Lipophilic and non-ionized
- D. Polar and charged
Correct answer: C. Lipophilic and non-ionized
10. A drug with a very high melting point is generally:
- A. Highly lipophilic
- B. Highly soluble in water
- C. Poorly soluble in most solvents
- D. Fast-acting
Correct answer: C. Poorly soluble in most solvents
11. The aqueous solubility of a drug can be increased by:
- A. Decreasing ionization
- B. Adding lipophilic groups
- C. Forming salts
- D. Increasing Log P
Correct answer: C. Forming salts
12. Which physicochemical property best predicts oral bioavailability?
- A. Log P
- B. Molecular weight
- C. Dissolution rate
- D. All of the above
Correct answer: D. All of the above
13. The partition coefficient (P) is defined as the ratio of drug concentration in:
- A. Blood to plasma
- B. Octanol to water
- C. Plasma to tissue
- D. GI fluid to blood
Correct answer: B. Octanol to water
14. What happens to the solubility of a weak base in acidic pH?
- A. Decreases
- B. Increases
- C. Unaffected
- D. Forms a precipitate
Correct answer: B. Increases
15. Which drug form is expected to dissolve faster?
- A. Coarse powder
- B. Micronized particles
- C. Crystalline form
- D. Suspension
Correct answer: B. Micronized particles
16. Which of the following is NOT a physicochemical property?
- A. Log P
- B. pKa
- C. Clearance
- D. Solubility
Correct answer: C. Clearance
17. Which physicochemical property affects protein binding of drugs?
- A. Color
- B. Lipophilicity
- C. pH of the stomach
- D. Osmolarity
Correct answer: B. Lipophilicity
18. Drug stability is most affected by:
- A. Molecular weight
- B. Melting point
- C. Hydrolysis and oxidation
- D. Taste
Correct answer: C. Hydrolysis and oxidation
19. A weakly basic drug is more unionized in which pH?
- A. 2
- B. 5
- C. 7
- D. 10
Correct answer: D. 10
20. A drug that is highly polar will likely have:
- A. High oral absorption
- B. Poor membrane permeability
- C. High lipid solubility
- D. CNS penetration
Correct answer: B. Poor membrane permeability
21. Lipinski’s Rule of Five helps predict:
- A. Drug cost
- B. Oral bioavailability
- C. Drug stability
- D. Metabolic pathways
Correct answer: B. Oral bioavailability
22. A drug violates Lipinski’s rules if it has:
- A. Molecular weight < 500
- B. More than 5 hydrogen bond donors
- C. Log P < 5
- D. Less than 10 hydrogen bond acceptors
Correct answer: B. More than 5 hydrogen bond donors
23. What is hygroscopicity in pharmaceuticals?
- A. Resistance to oxidation
- B. Ability to absorb moisture from air
- C. pH-dependent solubility
- D. Rate of dissolution
Correct answer: B. Ability to absorb moisture from air
24. The crystalline form of a drug usually has:
- A. Higher solubility than amorphous form
- B. Lower stability
- C. Higher melting point
- D. Greater permeability
Correct answer: C. Higher melting point
25. Solubility can be increased by forming a:
- A. Suspension
- B. Co-crystal
- C. Gel
- D. Cream
Correct answer: B. Co-crystal
26. Which of these properties affects the rate of passive diffusion across membranes?
- A. Molecular size
- B. Lipophilicity
- C. Ionization
- D. All of the above
Correct answer: D. All of the above
27. Why is knowledge of pKa important for pharmacists?
- A. It determines the drug’s half-life
- B. It helps optimize drug solubility and absorption
- C. It influences protein binding
- D. It determines renal clearance
Correct answer: B. It helps optimize drug solubility and absorption
28. Which is true for a weak acid in the stomach (pH ~1.5)?
- A. Mostly ionized
- B. Poorly absorbed
- C. Mostly unionized
- D. Fully soluble
Correct answer: C. Mostly unionized
29. A compound with Log P = 6 is likely to be:
- A. Very water-soluble
- B. Very lipophilic
- C. Easily excreted renally
- D. A strong acid
Correct answer: B. Very lipophilic
30. What is polymorphism in drugs?
- A. Structural mutation
- B. Different dosage forms
- C. Ability of a compound to exist in multiple crystalline forms
- D. Genetic variation
Correct answer: C. Ability of a compound to exist in multiple crystalline forms
31. What is the impact of high ionization on oral drug absorption?
- A. Increases it
- B. Decreases it
- C. No effect
- D. Makes it more stable
Correct answer: B. Decreases it
32. Which physicochemical property is most useful for topical drug delivery?
- A. High molecular weight
- B. High polarity
- C. Moderate lipophilicity
- D. High melting point
Correct answer: C. Moderate lipophilicity
33. The log D value of a drug refers to:
- A. Its ionic solubility
- B. Its permeability through skin
- C. Its distribution coefficient at a given pH
- D. Its therapeutic index
Correct answer: C. Its distribution coefficient at a given pH
34. A drug with poor aqueous solubility may benefit from:
- A. Forming a salt
- B. Freezing
- C. Tablet compression
- D. Higher melting point
Correct answer: A. Forming a salt
35. Ion trapping occurs when:
- A. The pH is uniform across membranes
- B. Drugs accumulate in compartments with a different pH
- C. The drug is unionized
- D. Log P is low
Correct answer: B. Drugs accumulate in compartments with a different pH
36. What is the effect of higher molecular weight on diffusion?
- A. Faster diffusion
- B. Slower diffusion
- C. No effect
- D. Increases absorption
Correct answer: B. Slower diffusion
37. A basic drug will ionize in:
- A. Alkaline environment
- B. Acidic environment
- C. Neutral environment
- D. All of the above
Correct answer: B. Acidic environment
38. Permeability across lipid membranes requires:
- A. Large polar molecules
- B. Unionized and lipophilic forms
- C. Highly charged molecules
- D. Low Log P values
Correct answer: B. Unionized and lipophilic forms
39. A zwitterion is a molecule that:
- A. Has no charge
- B. Has both positive and negative charges but is overall neutral
- C. Is a strong base
- D. Is fully lipophilic
Correct answer: B. Has both positive and negative charges but is overall neutral
40. Which formulation approach can enhance dissolution of poorly soluble drugs?
- A. Use of crystalline forms
- B. Use of co-solvents
- C. Decreasing particle size
- D. Both B and C
Correct answer: D. Both B and C
41. The BCS classification system classifies drugs based on:
- A. Half-life and bioavailability
- B. pKa and polarity
- C. Solubility and permeability
- D. Color and taste
Correct answer: C. Solubility and permeability
42. Which class in BCS represents high solubility and high permeability drugs?
- A. Class I
- B. Class II
- C. Class III
- D. Class IV
Correct answer: A. Class I
43. An acidic drug is more soluble in:
- A. Acidic pH
- B. Basic pH
- C. Neutral pH
- D. None of the above
Correct answer: B. Basic pH
44. Which property is most useful for designing extended-release formulations?
- A. High water solubility
- B. Short half-life
- C. Low solubility and controlled permeability
- D. High ionization
Correct answer: C. Low solubility and controlled permeability
45. The term “ion pair formation” is used to:
- A. Decrease solubility
- B. Improve membrane permeability
- C. Enhance protein binding
- D. Alter pKa
Correct answer: B. Improve membrane permeability
46. The measure of drug solubility in lipid vs. aqueous media is:
- A. Log P
- B. pKa
- C. Partition constant
- D. Both A and C
Correct answer: D. Both A and C
47. Increasing the temperature generally:
- A. Decreases solubility
- B. Has no effect
- C. Increases solubility of most solids
- D. Inactivates drug molecules
Correct answer: C. Increases solubility of most solids
48. Highly lipophilic drugs may show:
- A. Rapid renal clearance
- B. Slow distribution
- C. High volume of distribution
- D. Poor CNS penetration
Correct answer: C. High volume of distribution
49. Drug polymorphism can affect:
- A. Taste
- B. Color
- C. Solubility and bioavailability
- D. All of the above
Correct answer: C. Solubility and bioavailability
50. What does Log S refer to in drug development?
- A. pH stability
- B. Logarithmic solubility
- C. Speed of onset
- D. Stereoselectivity
Correct answer: B. Logarithmic solubility