Chemical properties of drugs determine how a molecule behaves in formulation, biological media, and during storage. For B.Pharm students, mastering concepts such as pKa, lipophilicity (logP/logD), solubility, ionization, chemical stability (hydrolysis, oxidation, photodegradation), tautomerism, stereochemistry, and salt formation is essential for rational drug design, pharmacokinetics, and formulation development. Understanding partitioning, buffer effects, polymorphism, and excipient compatibility links chemistry to absorption, distribution, metabolism, and stability. These keywords—pKa, solubility, lipophilicity, stability, Henderson-Hasselbalch, partition coefficient—are fundamental to predicting drug behavior. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which parameter best predicts passive membrane permeability of a neutral drug?
- pKa
- LogP (partition coefficient)
- Buffer capacity
- Hygroscopicity
Correct Answer: LogP (partition coefficient)
Q2. The Henderson-Hasselbalch equation relates pH to which drug property?
- Intrinsic dissolution rate
- Drug ionization (degree of ionization)
- Photostability
- Melting point
Correct Answer: Drug ionization (degree of ionization)
Q3. A weak acid drug with pKa 4.5 will be predominantly ionized at which pH?
- pH 2.0
- pH 4.5
- pH 7.4
- pH 3.5
Correct Answer: pH 7.4
Q4. LogD differs from logP because logD:
- Measures only neutral species partitioning
- Is independent of pH
- Accounts for ionized and unionized species at a given pH
- Is measured in solid state
Correct Answer: Accounts for ionized and unionized species at a given pH
Q5. Which chemical reaction commonly causes hydrolytic degradation of ester prodrugs?
- Photolysis
- Oxidation
- Hydrolysis
- Isomerization
Correct Answer: Hydrolysis
Q6. Which factor most increases solubility of a basic drug in aqueous solution?
- Raising the pH above pKa
- Lowering the pH below pKa
- Decreasing temperature
- Converting to a free base
Correct Answer: Lowering the pH below pKa
Q7. Which chemical property is directly affected by polymorphism?
- pKa value
- Melting point and solubility
- Optical rotation only
- Chemical formula
Correct Answer: Melting point and solubility
Q8. Tautomerism can influence:
- Only the physical state
- Reactivity, pKa, and binding interactions
- Elemental composition
- Color but not activity
Correct Answer: Reactivity, pKa, and binding interactions
Q9. Which statement about chiral centers in drugs is correct?
- Enantiomers always have identical pharmacological effects
- Stereochemistry can alter potency, metabolism, and toxicity
- Chirality only affects taste
- All drugs must be racemic mixtures
Correct Answer: Stereochemistry can alter potency, metabolism, and toxicity
Q10. Metal-catalyzed oxidation of drugs is commonly minimized by:
- Increasing exposure to light
- Adding chelating agents like EDTA
- Raising humidity
- Using basic pH buffers
Correct Answer: Adding chelating agents like EDTA
Q11. Which buffer system would most strongly resist pH change near pH 4.8?
- Phosphate buffer (pKa ~7.2)
- Acetate buffer (pKa ~4.8)
- Tris buffer (pKa ~8.1)
- Bicarbonate buffer (pKa ~6.1)
Correct Answer: Acetate buffer (pKa ~4.8)
Q12. A drug showing first-order degradation means:
- Degradation rate is constant over time
- Rate depends on drug concentration
- Rate depends on square of concentration
- Degradation stops after initial period
Correct Answer: Rate depends on drug concentration
Q13. Which molecule property increases likelihood of crossing the blood-brain barrier?
- High polar surface area and high molecular weight
- Low lipophilicity and high ionization
- Moderate lipophilicity and low ionization at physiological pH
- Strong protein binding only
Correct Answer: Moderate lipophilicity and low ionization at physiological pH
Q14. Salt formation of drugs is primarily used to:
- Decrease chemical stability
- Modify solubility and dissolution rate
- Change molecular weight
- Eliminate chirality
Correct Answer: Modify solubility and dissolution rate
Q15. Photodegradation of a drug molecule typically involves:
- Absorption of photons leading to excited states and bond cleavage
- Only conformational changes without chemical reaction
- Immediate precipitation
- pH-independent hydrolysis
Correct Answer: Absorption of photons leading to excited states and bond cleavage
Q16. Which analytical property is most useful for monitoring oxidative degradation?
- Melting point determination
- Peroxide value, HPLC detecting oxidized products
- pKa titration
- Refractive index
Correct Answer: Peroxide value, HPLC detecting oxidized products
Q17. Which term describes a drug’s tendency to absorb moisture from the air?
- Hygroscopicity
- Hydrophobicity
- Volatility
- Photostability
Correct Answer: Hygroscopicity
Q18. The intrinsic dissolution rate is most dependent on:
- Particle color
- Molecular structure and surface area under controlled conditions
- Amount of excipient present in bulk powder
- Ambient light intensity
Correct Answer: Molecular structure and surface area under controlled conditions
Q19. Which reaction pathway is common for tertiary amines under oxidative stress?
- Dealkylation to form secondary amines
- Oxidation to N-oxides
- Reduction to hydrocarbons
- Formation of esters
Correct Answer: Oxidation to N-oxides
Q20. Complexation with cyclodextrins is used to:
- Decrease aqueous solubility
- Improve solubility and stability of lipophilic drugs
- Promote crystallization
- Increase molecular weight dramatically
Correct Answer: Improve solubility and stability of lipophilic drugs
Q21. Which statement about acid-catalyzed hydrolysis is true?
- Occurs faster at very high pH only
- Rate increases as pH decreases when acid catalysis applies
- Is independent of temperature
- Prevents formation of any degradation products
Correct Answer: Rate increases as pH decreases when acid catalysis applies
Q22. Which feature most strongly contributes to a drug’s chemical stability in solid state?
- High surface area and amorphous form
- Stable crystalline polymorph with low hygroscopicity
- Presence of free radicals
- High residual solvent content
Correct Answer: Stable crystalline polymorph with low hygroscopicity
Q23. Which functional group is most susceptible to oxidation under ambient conditions?
- Tertiary amines
- Primary alcohols and phenols
- Alkanes without heteroatoms
- Perfluorinated groups
Correct Answer: Primary alcohols and phenols
Q24. A drug’s pKa equals the pH at which:
- 100% of drug is ionized
- 50% of the drug is ionized and 50% is unionized
- No drug is ionized
- The drug is completely insoluble
Correct Answer: 50% of the drug is ionized and 50% is unionized
Q25. Which excipient interaction would most likely accelerate hydrolysis of a labile ester drug?
- Addition of a nonionic surfactant
- Presence of basic excipient like magnesium stearate
- Use of inert fillers like microcrystalline cellulose
- Encapsulation in a protective polymer
Correct Answer: Presence of basic excipient like magnesium stearate
Q26. Keto-enol tautomerism affects which drug properties?
- Only the color
- pKa, reactivity, and binding to targets
- Only solubility in nonpolar solvents
- Molecular weight
Correct Answer: pKa, reactivity, and binding to targets
Q27. Which parameter is least likely to change when a drug forms a salt?
- Solubility in water
- Melting point
- Fundamental covalent structure of the drug molecule
- Rate of dissolution
Correct Answer: Fundamental covalent structure of the drug molecule
Q28. Which technique is best for distinguishing polymorphs of a drug substance?
- UV-visible spectroscopy
- X-ray powder diffraction (XRPD)
- Simple pH measurement
- Refractive index
Correct Answer: X-ray powder diffraction (XRPD)
Q29. Why are prodrugs used from a chemical property perspective?
- To permanently change drug’s active moiety
- To improve solubility, permeability, or chemical stability and then convert in vivo
- To eliminate need for metabolism
- To increase molecular weight without functional benefit
Correct Answer: To improve solubility, permeability, or chemical stability and then convert in vivo
Q30. Which approach reduces photodegradation risk in a liquid formulation?
- Use of clear glass bottles and storage in sunlight
- Addition of antioxidants and light-protective packaging
- Raising pH to extreme values irrespective of drug chemistry
- Increasing dissolved oxygen content
Correct Answer: Addition of antioxidants and light-protective packaging
