Physicochemical characteristics of drug substances MCQs With Answer

Understanding the physicochemical characteristics of drug substances is essential for B. Pharm students involved in formulation, stability, and biopharmaceutics. This concise overview highlights key properties — solubility, pKa, partition coefficient (log P/log D), dissolution rate, polymorphism, crystal habit, melting point, hygroscopicity, and chemical stability — and explains their impact on absorption, bioavailability, drug–excipient compatibility, and manufacturing. Emphasis is given to experimental methods (potentiometry, UV, DSC, XRD, shake‑flask) and practical strategies to optimize poorly soluble drugs (salt formation, solid dispersions, prodrugs). Mastery of these physicochemical attributes supports rational formulation design and regulatory submissions. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What does the partition coefficient (log P) represent for a drug substance?

• The ratio of ionized drug in water to ionized drug in octanol
• The ratio of un-ionized drug concentration in octanol to that in water
• The solubility of a drug in buffer at pH 7.4
• The dissolution rate of a drug particle

Correct Answer: The ratio of un-ionized drug concentration in octanol to that in water

Q2. Which form of the Henderson–Hasselbalch equation applies to a weak acid?

• pH = pKa + log [BH+]/[B]
• pH = pKa + log [A−]/[HA]
• pKa = pH + log [HA]/[A−]
• pH = pKa − log [A−]/[HA]

Correct Answer: pH = pKa + log [A−]/[HA]

Q3. How does ionization generally affect aqueous solubility of a drug?

• Ionization decreases aqueous solubility
• Ionization does not affect solubility
• Ionization increases aqueous solubility for most drugs
• Ionization increases solubility only in octanol

Correct Answer: Ionization increases aqueous solubility for most drugs

Q4. What is the distribution coefficient (log D)?

• Log P measured only for ionized species
• Log P adjusted for pH-dependent ionization including all species
• Solubility measured in two immiscible organic solvents
• The logarithm of intrinsic dissolution rate

Correct Answer: Log P adjusted for pH-dependent ionization including all species

Q5. According to the Noyes–Whitney equation, which factor increases dissolution rate?

• Decreasing surface area of drug particles
• Increasing diffusion layer thickness
• Increasing saturation solubility and surface area
• Lowering the diffusion coefficient

Correct Answer: Increasing saturation solubility and surface area

Q6. Why is salt formation commonly used in drug development?

• To reduce molecular weight
• To decrease chemical stability
• To increase aqueous solubility and dissolution rate
• To remove chirality

Correct Answer: To increase aqueous solubility and dissolution rate

Q7. How can polymorphism influence a drug substance?

• Polymorphism only affects color, not performance
• Different polymorphs can show different melting points and solubilities
• Polymorphism always improves bioavailability
• All polymorphs have identical stability

Correct Answer: Different polymorphs can show different melting points and solubilities

Q8. Which thermal technique is most appropriate to detect melting points and phase transitions?

• UV–Vis spectroscopy
• High-performance liquid chromatography
• Differential scanning calorimetry (DSC)
• Shake‑flask partitioning

Correct Answer: Differential scanning calorimetry (DSC)

Q9. What information does X-ray diffraction (XRD) primarily provide about a drug solid?

• Thermal degradation kinetics
• Crystalline structure and identification of polymorphs
• Moisture uptake over time
• Octanol–water partitioning

Correct Answer: Crystalline structure and identification of polymorphs

Q10. Hygroscopicity refers to a material’s tendency to:

• React with oxygen
• Absorb moisture from the environment
• Crystallize into more stable forms
• Partition into octanol

Correct Answer: Absorb moisture from the environment

Q11. The intrinsic dissolution rate (IDR) is measured under what key condition?

• Variable surface area to simulate powder dissolution
• Constant surface area of a compacted disk
• Using organic solvents only
• At a single pH where the drug is fully ionized

Correct Answer: Constant surface area of a compacted disk

Q12. Which of the following is a criterion of Lipinski’s rule of five?

• Molecular weight greater than 700
• More than 10 hydrogen bond donors
• Log P not greater than 5
• More than 15 rotatable bonds

Correct Answer: Log P not greater than 5

Q13. Potentiometric titration for pKa determination relies on detecting:

• Changes in UV spectra only
• Inflection points in the pH vs volume curve
• Temperature changes during titration
• Partitioning into octanol

Correct Answer: Inflection points in the pH vs volume curve

Q14. The shake‑flask method is a classical technique used to measure:

• Intrinsic dissolution rate
• Partition coefficient (log P)
• Melting point
• Hygroscopicity index

Correct Answer: Partition coefficient (log P)

Q15. The Biopharmaceutics Classification System (BCS) categorizes drugs based on:

• Spectrum of antimicrobial activity
• Solubility and intestinal permeability
• Degree of ionization only
• Molecular optical rotation

Correct Answer: Solubility and intestinal permeability

Q16. How does a very high log P generally affect oral drug absorption?

• Always improves absorption because solubility increases
• May increase membrane permeability but often reduces aqueous solubility and absorption
• Has no effect on absorption
• Prevents drug from crossing lipid membranes

Correct Answer: May increase membrane permeability but often reduces aqueous solubility and absorption

Q17. A zwitterionic drug molecule contains:

• Only negative charges at all pH values
• Both positive and negative charges within the same molecule
• Only neutral functional groups
• Only positively charged groups

Correct Answer: Both positive and negative charges within the same molecule

Q18. For a weak base, solubility typically increases when the pH is:

• Much higher than the pKa
• Much lower than the pKa
• Equal to the isoelectric point
• Irrelevant to pKa

Correct Answer: Much lower than the pKa

Q19. Compared to a crystalline form, the amorphous form of a drug typically shows:

• Lower apparent solubility and faster recrystallization
• Higher apparent solubility and higher free energy
• Identical solubility but lower dissolution rate
• Greater chemical stability

Correct Answer: Higher apparent solubility and higher free energy

Q20. Which formulation approach primarily increases dissolution rate by reducing particle size?

• Salt formation
• Micronization or nanosizing
• Solid dispersion with polymer
• Hydrolysis

Correct Answer: Micronization or nanosizing

Q21. A prodrug strategy is employed to:

• Increase chemical inertness without metabolic conversion
• Improve solubility, permeability or targeting via biotransformation to the active drug
• Convert an active drug into an inactive impurity
• Reduce the molecular weight permanently

Correct Answer: Improve solubility, permeability or targeting via biotransformation to the active drug

Q22. How does particle size reduction affect absorption for poorly soluble drugs?

• It always decreases absorption due to aggregation
• It increases dissolution rate and can enhance absorption
• It converts crystalline drug to non-crystalline instantly
• It increases melting point significantly

Correct Answer: It increases dissolution rate and can enhance absorption

Q23. At physiological pH (7.4), a weak base with pKa 9 will be predominantly:

• Unionized and very lipophilic
• Predominantly ionized in aqueous solution
• Completely non-existent
• Converted to its crystalline form

Correct Answer: Predominantly ionized in aqueous solution

Q24. Micellar solubilization enhances apparent solubility by:

• Breaking covalent bonds in the drug
• Entrapping drug molecules in micelle cores
• Increasing drug melting point
• Changing the drug’s pKa permanently

Correct Answer: Entrapping drug molecules in micelle cores

Q25. Which statement about log P is correct?

• Log P is measured as the logarithm of the ratio of activity coefficients in water
• Log P is a dimensionless logarithm of the concentration ratio of a neutral compound between octanol and water
• Log P has units of mol/L
• Log P increases when a compound becomes more polar

Correct Answer: Log P is a dimensionless logarithm of the concentration ratio of a neutral compound between octanol and water

Q26. Which condition is most likely to accelerate hydrolytic degradation of a drug substance?

• Low moisture content and dry storage
• High humidity and presence of moisture
• Storing at sub-zero temperatures
• Packaging under inert dry gas

Correct Answer: High humidity and presence of moisture

Q27. Thermogravimetric analysis (TGA) primarily measures:

• Heat flow associated with phase transitions
• Mass change of a sample as a function of temperature
• Optical absorbance across the UV range
• Partitioning into organic solvents

Correct Answer: Mass change of a sample as a function of temperature

Q28. Which form of a drug generally permeates lipid membranes most readily?

• The fully ionized form
• The zwitterionic form always
• The unionized (neutral) form
• The crystalline solid form in the GI lumen

Correct Answer: The unionized (neutral) form

Q29. Why is pH adjustment used in liquid formulations?

• To ensure the drug is completely insoluble
• To optimize solubility and chemical stability of the drug substance
• To increase the viscosity regardless of stability
• To convert the API into a different polymorph

Correct Answer: To optimize solubility and chemical stability of the drug substance

Q30. For reliable salt formation between an acid and a base, which pKa relationship is generally recommended?

• The pKa difference should be less than 0.5
• The pKa difference should be approximately equal to 0
• The pKa of the acid must be greater than the base’s pKa
• The pKa difference (acid pKa − base pKa) should be greater than about 2

Correct Answer: The pKa difference (acid pKa − base pKa) should be greater than about 2

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