Solvent effect on drug stability MCQs With Answer

Introduction: Understanding the solvent effect on drug stability is vital for B. Pharm students involved in formulation, stability testing, and shelf-life prediction. Solvent polarity, protic versus aprotic behavior, dielectric constant, hydrogen-bonding capacity, and cosolvent compositions influence degradation pathways such as hydrolysis, oxidation, and solvolysis. Knowledge of parameters like Kamlet–Taft and Reichardt’s ET(30), water activity, and solvent viscosity guides rational solvent selection for assays, lyophilization, and accelerated stability studies. Practical insight into solvent–drug interactions helps prevent unwanted decomposition and optimize drug delivery systems. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which solvent property most directly stabilizes a charged transition state and can thereby accelerate a reaction involving polar intermediates?

• Dielectric constant
• Viscosity
• Boiling point
• Surface tension

Correct Answer: Dielectric constant

Q2. Protic solvents often increase the rate of which degradation pathway for ester-containing drugs?

• Photodegradation
• Hydrolysis
• Thermal isomerization
• Oxidative cleavage

Correct Answer: Hydrolysis

Q3. In an aprotic polar solvent (e.g., DMSO), which reaction type is typically faster compared with a protic solvent?

• SN1 solvolysis of tertiary substrates
• SN2 nucleophilic substitution
• Acid-catalyzed hydrolysis
• Radical polymerization

Correct Answer: SN2 nucleophilic substitution

Q4. Which Kamlet–Taft parameter quantifies a solvent’s hydrogen-bond donating ability?

• pi* (dipolarity/polarizability)
• alpha (hydrogen-bond donor)
• beta (hydrogen-bond acceptor)
• ET(30)

Correct Answer: alpha (hydrogen-bond donor)

Q5. Adding a water-miscible cosolvent (e.g., ethanol) to an aqueous formulation primarily affects drug stability by changing:

• Ambient humidity
• Solvent polarity and water activity
• Drug molecular weight
• Container closure system

Correct Answer: Solvent polarity and water activity

Q6. Solvolysis rates for a given drug are often correlated with which empirical solvent scale?

• Hildebrand solubility parameter
• Reichardt’s ET(30) polarity scale
• pKa scale
• Hansen solubility parameters

Correct Answer: Reichardt’s ET(30) polarity scale

Q7. Which solvent characteristic would most likely slow down a diffusion-limited degradation reaction?

• Low dielectric constant
• High viscosity
• High volatility
• Low refractive index

Correct Answer: High viscosity

Q8. For peptide drugs, organic solvents like acetonitrile can cause instability primarily due to:

• Promotion of disulfide bond formation
• Denaturation and aggregation
• Increasing enzymatic activity
• Lowering glass transition temperature

Correct Answer: Denaturation and aggregation

Q9. Which solvent property most influences the rate of oxidation by molecular oxygen in solution?

• Dielectric constant
• Oxygen solubility
• Surface tension
• Color

Correct Answer: Oxygen solubility

Q10. In stability studies, residual organic solvents in formulations are a concern because they can:

• Act as antioxidants
• Promote chemical degradation and toxicity
• Increase melting point
• Reduce solubility of active ingredient

Correct Answer: Promote chemical degradation and toxicity

Q11. Which solvent environment typically favors SN1-like solvolysis for a benzylic ester?

• Nonpolar aprotic solvent
• Polar protic solvent
• High-viscosity ionic liquid
• Supercritical CO2

Correct Answer: Polar protic solvent

Q12. Which analytical parameter helps predict how solvent polarity affects UV–Vis absorbance shifts for chromophoric drugs?

• Partition coefficient (log P)
• Solvatochromic shift (ET(30) correlation)
• Melting point
• Viscosity index

Correct Answer: Solvatochromic shift (ET(30) correlation)

Q13. Water activity (aw) in a formulation influences chemical stability by affecting:

• Optical rotation
• Rate of hydrolytic reactions
• Polymer crystallinity only
• Ion-pairing in organic solvents

Correct Answer: Rate of hydrolytic reactions

Q14. Which solvent type is generally better at stabilizing radical intermediates due to high polarizability?

• Nonpolar alkanes
• Polarizable aromatic solvents (e.g., toluene)
• Protic alcohols
• Supercritical water

Correct Answer: Polarizable aromatic solvents (e.g., toluene)

Q15. When choosing a solvent for lyophilization of a small-molecule API, which factor is most critical for product stability?

• Solvent’s refractive index
• Glass transition temperature of the frozen matrix
• Color of solvent
• Solvent odor

Correct Answer: Glass transition temperature of the frozen matrix

Q16. Which cosolvent strategy can be used to reduce hydrolysis of a water-sensitive drug in solution?

• Increase temperature
• Replace part of water with an aprotic organic cosolvent
• Increase ionic strength with NaCl
• Expose to light to drive photostability

Correct Answer: Replace part of water with an aprotic organic cosolvent

Q17. Which experimental change would help determine whether solvent polarity affects the transition state of a degradation reaction?

• Measure reaction rate in solvents with varying ET(30) values
• Measure melting point in each solvent
• Determine solubility only in one solvent
• Change container material

Correct Answer: Measure reaction rate in solvents with varying ET(30) values

Q18. Solvent-mediated pKa shifts can alter stability because:

• They change the drug’s ionization state and reactivity
• They change molecular weight
• They convert drug into a polymer
• They always prevent oxidation

Correct Answer: They change the drug’s ionization state and reactivity

Q19. Surfactant micelles in solvent systems affect drug stability primarily by:

• Changing the drug’s local microenvironment and protection from water
• Altering the atomic number of elements
• Increasing ambient temperature
• Removing drug entirely from solution permanently

Correct Answer: Changing the drug’s local microenvironment and protection from water

Q20. Which solvent parameter is most useful for predicting nucleophilicity of solvent molecules during solvolysis?

• Viscosity
• Kamlet–Taft beta (H-bond acceptor)
• Boiling point
• Surface tension

Correct Answer: Kamlet–Taft beta (H-bond acceptor)

Q21. In accelerated stability testing, replacing water with deuterated water (D2O) can provide mechanistic insight because:

• D2O evaporates faster
• Isotope effects alter hydrolysis rates revealing mechanism
• D2O is a stronger oxidant
• D2O changes pH to 7.5 automatically

Correct Answer: Isotope effects alter hydrolysis rates revealing mechanism

Q22. Which solvent is commonly avoided in aqueous pharmaceutical formulations due to peroxidation risk increasing oxidative degradation?

• Glycerol
• Petroleum ether
• Unsaturated ethers like diethyl ether
• Isopropyl alcohol

Correct Answer: Unsaturated ethers like diethyl ether

Q23. How does increasing solvent polarity generally affect the rate of acid-catalyzed hydrolysis for an ionic substrate?

• Has no effect
• Usually accelerates by stabilizing charged intermediates
• Slows down by increasing viscosity only
• Causes precipitation and stops reaction

Correct Answer: Usually accelerates by stabilizing charged intermediates

Q24. Which solvent choice is preferred to minimize hydrolytic degradation during sample storage for HPLC analysis?

• Pure water
• Acidified aqueous buffer at elevated temperature
• Appropriate organic solvent or organic-aqueous mixture refrigerated
• Undiluted concentrated acid

Correct Answer: Appropriate organic solvent or organic-aqueous mixture refrigerated

Q25. Partitioning of a drug into an organic phase during extraction can affect observed stability because:

• Organic phases always catalyze reactions
• The drug experiences a different microenvironment and reactivity
• The drug’s molecular formula changes
• It becomes radioactive

Correct Answer: The drug experiences a different microenvironment and reactivity

Q26. Which solvent factor can protect photosensitive drugs from photodegradation?

• High transparency to UV
• Presence of UV-absorbing solvent or additives
• Low boiling point
• High refractive index

Correct Answer: Presence of UV-absorbing solvent or additives

Q27. Ionic liquids as solvents may improve stability of some APIs due to:

• Extremely low polarity always causing precipitation
• Tunable polarity and strong solvation of specific species
• High volatility which removes water
• They are always basic and neutralize acids

Correct Answer: Tunable polarity and strong solvation of specific species

Q28. Which experimental observation suggests that solvent hydrogen-bonding is important for a drug’s degradation?

• Rate is identical in protic and aprotic solvents
• Rate correlates with solvent alpha and beta parameters
• No change in rate with temperature
• The drug changes color only

Correct Answer: Rate correlates with solvent alpha and beta parameters

Q29. During formulation development, choosing a solvent with low oxygen solubility can help reduce:

• Hydrolytic cleavage
• Oxidative degradation
• pH drift
• Viscosity increases

Correct Answer: Oxidative degradation

Q30. Which approach is best to evaluate the specific effect of solvent polarity on a drug’s hydrolysis kinetics?

• Measure kinetics in solvents of varying polarity while keeping water concentration constant
• Measure only solubility at room temperature
• Change container lids and repeat
• Measure kinetics at only one solvent composition

Correct Answer: Measure kinetics in solvents of varying polarity while keeping water concentration constant