Solubility and biological action MCQs With Answer are essential for B. Pharm students preparing for exams and practical pharmacy practice. This concise, keyword-rich introduction covers drug solubility, dissolution, pH‑solubility profiles, partition coefficient (log P/log D), bioavailability, and how solubility affects biological action and therapeutic response. Understanding factors such as salt formation, particle size, polymorphism, complexation, surfactants, and formulation strategies is vital to predict absorption and clinical effect. These MCQs focus on core concepts, measurement methods, and formulation approaches to enhance learning and exam readiness. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is the definition of aqueous solubility of a drug?
- The maximum amount of drug that can dissolve in a solvent at equilibrium at a given temperature
- The rate at which a drug dissolves in the gastrointestinal tract
- The partitioning of drug between octanol and water
- The pH at which a drug is 50% ionized
Correct Answer: The maximum amount of drug that can dissolve in a solvent at equilibrium at a given temperature
Q2. Which equation relates dissolution rate to surface area and concentration gradient?
- Henderson-Hasselbalch equation
- Noyes–Whitney equation
- Michealis-Menten equation
- Arrhenius equation
Correct Answer: Noyes–Whitney equation
Q3. How does pH affect the solubility of a weakly acidic drug?
- Solubility increases as pH decreases
- Solubility increases as pH increases above pKa
- Solubility is independent of pH
- Solubility is maximum at pH equal to 0
Correct Answer: Solubility increases as pH increases above pKa
Q4. Which parameter describes lipophilicity measured as concentration ratio between octanol and water for the unionized form?
- pKa
- Log D
- Log P
- Intrinsic solubility
Correct Answer: Log P
Q5. What is intrinsic solubility (S0)?
- Solubility of the ionized form of a drug
- Solubility of the unionized form in pure water
- Solubility measured in octanol
- Solubility at elevated temperature only
Correct Answer: Solubility of the unionized form in pure water
Q6. Which method is commonly used to determine equilibrium solubility in the lab?
- Shake-flask method
- Thin layer chromatography
- Gas chromatography
- UV-visible spectroscopy without equilibration
Correct Answer: Shake-flask method
Q7. Henderson‑Hasselbalch equation is used to predict:
- Drug melting point
- pH-dependent ionization and apparent solubility
- Permeability across membranes
- Viscosity of solutions
Correct Answer: pH-dependent ionization and apparent solubility
Q8. Which strategy is most appropriate to improve solubility of a weakly basic drug?
- Form the free base and increase lipophilicity
- Convert to a salt with an acidic counterion
- Reduce aqueous pH
- Remove hydrogen bond donors
Correct Answer: Convert to a salt with an acidic counterion
Q9. What effect does micelle formation by surfactants have on solubility?
- Decreases solubility of lipophilic drugs
- Increases apparent solubility of lipophilic drugs
- Has no effect on solubility
- Only affects ionic strength
Correct Answer: Increases apparent solubility of lipophilic drugs
Q10. Which solid-state property often increases apparent solubility and dissolution rate?
- Highly crystalline structure
- Polymorphic form with higher lattice energy
- Amorphous form
- Large particle size
Correct Answer: Amorphous form
Q11. The term ‘supersaturation’ refers to:
- Solution pH equal to pKa
- Concentration above equilibrium solubility
- Maximum solubility at boiling point
- Concentration below intrinsic solubility
Correct Answer: Concentration above equilibrium solubility
Q12. Which effect does particle size reduction (micronization) primarily have?
- Increases melting point
- Decreases surface area and slows dissolution
- Increases surface area and accelerates dissolution
- Converts crystalline to amorphous form automatically
Correct Answer: Increases surface area and accelerates dissolution
Q13. Log D differs from log P because:
- Log D ignores pH effects
- Log D accounts for ionization at a given pH
- Log D is measured only in octanol
- Log D is the same as intrinsic solubility
Correct Answer: Log D accounts for ionization at a given pH
Q14. Which technique enhances solubility by forming inclusion complexes?
- Cyclodextrin complexation
- Freeze-drying without excipients
- Salt precipitation
- Dry granulation
Correct Answer: Cyclodextrin complexation
Q15. Which statement best describes the free drug hypothesis?
- Only protein-bound drug is pharmacologically active
- Only the unbound (free) drug is available for action and clearance
- Total drug concentration determines pharmacological effect
- Drugs must be lipophilic to be free
Correct Answer: Only the unbound (free) drug is available for action and clearance
Q16. Which factor does NOT significantly affect drug solubility?
- Crystal lattice energy
- Particle morphology
- Color of the drug powder
- Hydrogen bonding capacity
Correct Answer: Color of the drug powder
Q17. Which formulation approach uses lipids to improve oral absorption of poorly water-soluble drugs?
- Solid dispersions in polymers
- Lipid-based formulations (self-emulsifying drug delivery systems)
- Tablet compaction without excipients
- Salt formation with inorganic bases
Correct Answer: Lipid-based formulations (self-emulsifying drug delivery systems)
Q18. The Henderson-Hasselbalch equation for a weak acid includes which variables?
- pH, pKa, and ratio of ionized to unionized form
- Temperature and viscosity only
- Surface area and diffusion coefficient
- Log P and intrinsic solubility only
Correct Answer: pH, pKa, and ratio of ionized to unionized form
Q19. Which BCS class describes drugs with low solubility and high permeability?
- Class I
- Class II
- Class III
- Class IV
Correct Answer: Class II
Q20. How does protein binding influence biological action?
- Increases free drug concentration and potency
- Decreases free drug concentration and may reduce immediate effect
- Has no impact on distribution
- Only affects stability, not activity
Correct Answer: Decreases free drug concentration and may reduce immediate effect
Q21. Which analytical method can be used to measure solubility and detect precipitation kinetics?
- Dynamic light scattering for particle size only
- UV-visible spectroscopy with sampling after equilibration
- Electrocardiography
- Western blotting
Correct Answer: UV-visible spectroscopy with sampling after equilibration
Q22. Formation of which solid form typically reduces solubility compared to another form?
- Metastable polymorph versus stable polymorph
- Stable polymorph versus metastable polymorph
- Amorphous form versus crystalline form
- Nanosuspension versus micronized powder
Correct Answer: Stable polymorph versus metastable polymorph
Q23. Which is a primary reason to prepare a drug as a salt?
- To increase melting point
- To improve aqueous solubility and dissolution rate
- To change pharmacological target
- To eliminate the need for excipients
Correct Answer: To improve aqueous solubility and dissolution rate
Q24. The apparent solubility of a weak base in an acidic medium is usually:
- Lower than intrinsic solubility
- Higher than intrinsic solubility due to ionization
- Equal to its log P
- Independent of pH
Correct Answer: Higher than intrinsic solubility due to ionization
Q25. Which process is most likely rate-limiting for absorption of a BCS Class II drug?
- Permeation across intestinal mucosa
- Dissolution in gastrointestinal fluids
- Hepatic metabolism
- Renal excretion
Correct Answer: Dissolution in gastrointestinal fluids
Q26. Which excipient improves wetting and can enhance dissolution?
- Hydrophobic lubricant only
- Surfactants like polysorbate 80
- Colorants
- Magnesium oxide
Correct Answer: Surfactants like polysorbate 80
Q27. Which phenomenon explains reduced solubility at high ionic strength for some drugs?
- Common-ion effect and salt precipitation
- No effect of ions on solubility
- Increase in melting point
- Enhanced hydrogen bonding with water
Correct Answer: Common-ion effect and salt precipitation
Q28. What is the effect of temperature on solubility for most solids?
- Solubility decreases with increasing temperature for most solids
- Solubility increases with increasing temperature for most solids
- Temperature has no effect on solubility
- Solubility is solely determined by pH
Correct Answer: Solubility increases with increasing temperature for most solids
Q29. Which term describes the amount of drug dissolved per unit time per unit surface area under standardized conditions?
- Intrinsic dissolution rate
- Permeability coefficient
- pKa value
- Distribution volume
Correct Answer: Intrinsic dissolution rate
Q30. Which modification can increase solubility without chemical change to the drug molecule?
- Prodrug synthesis
- Amorphous solid dispersion with polymer
- Alkylation of aromatic ring
- Formation of a covalent conjugate
Correct Answer: Amorphous solid dispersion with polymer
Q31. Which statement best links solubility to bioavailability?
- Poor solubility always gives 100% bioavailability
- Poor solubility can limit absorption and reduce bioavailability
- Bioavailability depends only on metabolism, not solubility
- High solubility guarantees rapid therapeutic effect regardless of permeability
Correct Answer: Poor solubility can limit absorption and reduce bioavailability
Q32. Cyclodextrins improve solubility by:
- Forming ionic salts
- Encapsulating hydrophobic moieties within their cavity
- Increasing pH to extreme values
- Degrading the drug
Correct Answer: Encapsulating hydrophobic moieties within their cavity
Q33. Which parameter is used to quantify the strength of drug–protein binding?
- Partition coefficient log P only
- Binding constant (Ka) or fraction unbound (fu)
- Intrinsic dissolution rate
- pH maximum
Correct Answer: Binding constant (Ka) or fraction unbound (fu)
Q34. Which statement about prodrugs is correct regarding solubility?
- Prodrugs always decrease solubility
- Prodrugs can be designed to increase water solubility and improve absorption
- Prodrugs convert drugs to proteins
- Prodrugs have no impact on pharmacokinetics
Correct Answer: Prodrugs can be designed to increase water solubility and improve absorption
Q35. Which is a potential risk when a drug becomes supersaturated in the GI tract?
- Improved chemical stability
- Precipitation and reduced absorption
- Permanent solubilization
- Reduced permeability
Correct Answer: Precipitation and reduced absorption
Q36. Nephelometry is primarily used to assess:
- Therapeutic index
- Suspension turbidity and precipitation onset
- Melting point depression
- Viscosity of oil phases
Correct Answer: Suspension turbidity and precipitation onset
Q37. Which change increases drug dissolution rate according to Noyes–Whitney?
- Decrease diffusion coefficient
- Increase solvent viscosity
- Decrease surface area
- Increase concentration gradient (Cs – C)
Correct Answer: Increase concentration gradient (Cs – C)
Q38. Which design is best to study intrinsic dissolution rate?
- Powder dispersion in beaker without compression
- Compressed disc of drug with fixed surface area
- Shake-flask method with variable surface area
- Octanol partitioning experiment
Correct Answer: Compressed disc of drug with fixed surface area
Q39. Which factor often correlates inversely with aqueous solubility?
- High polarity
- High molecular weight and lipophilicity
- Presence of ionizable groups
- Low melting point
Correct Answer: High molecular weight and lipophilicity
Q40. Why are amorphous forms usually more soluble than corresponding crystalline forms?
- They have higher lattice energy
- They lack long-range order and have higher free energy
- They always convert immediately to stable crystal
- They contain more impurities only
Correct Answer: They lack long-range order and have higher free energy
Q41. Which is a common in vitro model to evaluate permeability relevant to biological action?
- PAMPA (Parallel Artificial Membrane Permeability Assay)
- Shake-flask solubility only
- Gas chromatography
- Western blot
Correct Answer: PAMPA (Parallel Artificial Membrane Permeability Assay)
Q42. What is the primary reason for conducting pH-solubility profiles?
- To measure melting point at different pH
- To predict drug solubility and ionization across GI tract pH range
- To determine color changes with pH
- To avoid performing dissolution tests
Correct Answer: To predict drug solubility and ionization across GI tract pH range
Q43. Co-crystals enhance solubility by:
- Covalently modifying the drug molecule
- Forming a crystalline complex with a coformer that alters lattice energy
- Increasing particle size dramatically
- Reducing pH in the GI tract
Correct Answer: Forming a crystalline complex with a coformer that alters lattice energy
Q44. Which of the following best describes partition coefficient (P)?
- Concentration ratio of ionized drug between water and octanol
- Concentration ratio of unionized drug between octanol and water
- Intrinsic dissolution rate divided by molecular weight
- Logarithm of aqueous solubility
Correct Answer: Concentration ratio of unionized drug between octanol and water
Q45. Which stabilization strategy helps maintain supersaturation and improve absorption?
- Use of precipitation inhibitors like polymers
- Increasing drug crystallinity
- Eliminating all excipients
- Reducing GI transit time
Correct Answer: Use of precipitation inhibitors like polymers
Q46. Which in vivo factor can reduce the effective solubility of a drug in the intestine?
- Presence of bile salts only increases solubility
- Food components, pH variations, and enzymes can alter solubility
- Intestinal motility has no effect
- Blood flow changes immediately change solubility
Correct Answer: Food components, pH variations, and enzymes can alter solubility
Q47. Which of the following is an example of a solubility-enhancing chemical modification?
- Forming ester prodrugs to increase hydrophilicity
- Increasing aromatic ring count
- Removing polar functional groups
- Converting to a larger hydrophobic analog
Correct Answer: Forming ester prodrugs to increase hydrophilicity
Q48. Which technique can predict precipitation tendency during rapid dilution in GI fluids?
- Supersaturation and precipitation kinetics studies (dilution tests)
- Simple pH measurement without dissolution
- Colorimetric assay of solid drug
- Measuring viscosity only
Correct Answer: Supersaturation and precipitation kinetics studies (dilution tests)
Q49. Which property is most directly linked to a drug’s ability to cross biological membranes by passive diffusion?
- High aqueous solubility only
- Appropriate balance of lipophilicity and polarity (optimal log P/log D)
- High molecular weight greater than 2000 Da
- Complete ionization at physiological pH always
Correct Answer: Appropriate balance of lipophilicity and polarity (optimal log P/log D)
Q50. In formulation development, which combined approach is often used for very poorly soluble drugs?
- Crystallization to the most stable form only
- Combination of particle size reduction, salt or prodrug formation, and use of solubilizers or solid dispersions
- Elimination of dissolution testing
- Use of insoluble excipients exclusively
Correct Answer: Combination of particle size reduction, salt or prodrug formation, and use of solubilizers or solid dispersions
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