Ionic strength and drug stability MCQs With Answer

Ionic strength influences electrostatic interactions, activity coefficients, solubility, and degradation pathways of drugs in solution. For B. Pharm students, understanding ionic strength, its calculation (I = 1/2 Σ ci zi²), Debye–Hückel behavior, Hofmeister effects, buffer composition, and excipient choices is essential for formulation design and stability testing. Changes in ionic strength alter reaction rates, protein aggregation, micelle formation and apparent pKa, affecting shelf life and in vivo performance. This concise review emphasizes practical implications: ionic strength calculation, experimental estimation (conductivity), and strategies to control ionic environments in formulations to enhance drug stability. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the correct formula for ionic strength (I) of a solution?

• I = Σ ci zi
• I = 1/2 Σ ci zi²
• I = Σ ci / zi
• I = √(Σ ci zi²)

Correct Answer: I = 1/2 Σ ci zi²

Q2. What are the units of ionic strength?

• Unitless
• Seconds (s)
• Molar (mol·L⁻¹)
• Pascal (Pa)

Correct Answer: Molar (mol·L⁻¹)

Q3. What is the ionic strength of a 0.10 M NaCl solution?

• 0.05 M
• 0.10 M
• 0.20 M
• 0.15 M

Correct Answer: 0.10 M

Q4. Calculate the ionic strength of 0.01 M CaCl₂.

• 0.01 M
• 0.02 M
• 0.03 M
• 0.04 M

Correct Answer: 0.03 M

Q5. How does increasing ionic strength generally affect electrostatic interactions between charged drug molecules?

• Enhances electrostatic attraction and repulsion
• Decreases electrostatic interactions by screening charges
• Converts electrostatic forces into covalent bonds
• Has no effect on electrostatic interactions

Correct Answer: Decreases electrostatic interactions by screening charges

Q6. What happens to the Debye length (electrical double layer thickness) when ionic strength increases?

• Debye length increases
• Debye length decreases
• Debye length becomes infinite
• Debye length is unaffected

Correct Answer: Debye length decreases

Q7. How do ionic activity coefficients typically change as ionic strength increases (in dilute solutions)?

• Activity coefficients increase substantially above 1
• Activity coefficients decrease (move away from ideality)
• Activity coefficients become negative
• Activity coefficients remain constant

Correct Answer: Activity coefficients decrease (move away from ideality)

Q8. Which concept orders ions according to their effect on protein stability and solubility?

• Debye–Hückel series
• Hofmeister series
• Arrhenius series
• Nernst series

Correct Answer: Hofmeister series

Q9. High ionic strength commonly causes which effect on proteins in solution?

• Salting-in (increased solubility) only
• Salting-out (precipitation) at sufficiently high salt
• Total denaturation without aggregation
• Complete stabilization against degradation

Correct Answer: Salting-out (precipitation) at sufficiently high salt

Q10. For a reaction between two similarly charged ions, increasing ionic strength will usually:

• Decrease the reaction rate by stronger repulsion
• Increase the reaction rate by reducing repulsion
• Have no effect on reaction rate
• Cause reaction to reverse spontaneously

Correct Answer: Increase the reaction rate by reducing repulsion

Q11. What is the ionic strength of 0.02 M MgCl₂?

• 0.02 M
• 0.04 M
• 0.06 M
• 0.08 M

Correct Answer: 0.06 M

Q12. Which parameter related to ionization is most affected by changes in ionic strength?

• Intrinsic solubility (always unchanged)
• Apparent pKa (ionization constant seen experimentally)
• Thermal decomposition point
• Absolute molecular weight

Correct Answer: Apparent pKa (ionization constant seen experimentally)

Q13. Which is the most direct way to estimate ionic strength for a pharmaceutical formulation?

• Direct pH measurement
• Calculation from known ionic composition
• UV-visible spectrophotometry
• Colorimetric test

Correct Answer: Calculation from known ionic composition

Q14. Typical ionic strength of human blood plasma is approximately:

• 0.01 M
• 0.05 M
• 0.15 M
• 1.00 M

Correct Answer: 0.15 M

Q15. Increasing ionic strength often affects protein aggregation how?

• Always prevents aggregation
• Has no effect on aggregation
• Can promote aggregation by screening repulsive charges
• Causes proteins to become covalently cross-linked

Correct Answer: Can promote aggregation by screening repulsive charges

Q16. How does ionic strength influence the apparent solubility of ionic drugs?

• Only temperature affects solubility, not ionic strength
• Ionic strength changes activity coefficients and thus apparent solubility
• Ionic strength always increases solubility regardless of drug
• Ionic strength converts ionic drugs to neutral form

Correct Answer: Ionic strength changes activity coefficients and thus apparent solubility

Q17. The Debye–Hückel limiting law is valid mainly at ionic strengths:

• Greater than 1.0 M
• Around 0.1–1.0 M
• Less than about 0.01 M
• At any ionic strength

Correct Answer: Less than about 0.01 M

Q18. Buffer capacity is primarily determined by:

• Ionic strength only
• Buffer concentration and pH
• Color of buffer solution
• Viscosity of the solution

Correct Answer: Buffer concentration and pH

Q19. Which mechanism explains how ionic strength can alter drug degradation rates?

• Screening of charged reactive species and ionic catalysis
• Only by changing atmospheric pressure
• By changing molecular weight of drug
• By altering the drug’s chemical formula

Correct Answer: Screening of charged reactive species and ionic catalysis

Q20. In the ionic strength expression I = 1/2 Σ ci zi², which quantity is squared?

• Concentration (ci)
• Charge number (zi)
• Temperature (T)
• Volume (V)

Correct Answer: Charge number (zi)

Q21. Which excipient will increase ionic strength most per mole when added to an aqueous drug formulation?

• Sucrose
• Mannitol
• NaCl
• Glycerol

Correct Answer: NaCl

Q22. Addition of NaCl to an ionic surfactant solution (e.g., SDS) typically causes:

• An increase in critical micelle concentration (CMC)
• A decrease in CMC
• Complete suppression of micelle formation
• No change in CMC ever

Correct Answer: A decrease in CMC

Q23. What distinguishes ionic strength from osmolarity?

• Ionic strength counts particles but ignores charge
• Ionic strength weights each ion by the square of its charge (z²)
• Osmolarity weights ions by z²
• They are identical concepts

Correct Answer: Ionic strength weights each ion by the square of its charge (z²)

Q24. Why is controlling ionic strength important during formulation development?

• It affects drug stability, aggregation and electrostatic interactions
• It changes the atomic number of elements
• It only affects color, not stability
• It is irrelevant to pharmaceutical formulations

Correct Answer: It affects drug stability, aggregation and electrostatic interactions

Q25. Increasing ionic strength typically affects zeta potential by:

• Increasing the magnitude of zeta potential
• Decreasing the magnitude of zeta potential (screening)
• Reversing sign of zeta potential only
• Having no effect at all

Correct Answer: Decreasing the magnitude of zeta potential (screening)

Q26. What is the ionic strength of a mixture containing 0.02 M NaCl and 0.01 M CaCl₂?

• 0.02 M
• 0.03 M
• 0.05 M
• 0.08 M

Correct Answer: 0.05 M

Q27. Per mole added, which ion contributes most to ionic strength?

• Sodium ion (Na⁺)
• Calcium ion (Ca²⁺)
• Chloride ion (Cl⁻)
• Glucose (neutral)

Correct Answer: Calcium ion (Ca²⁺)

Q28. During accelerated stability testing, uncontrolled changes in ionic strength can cause:

• No noticeable changes in degradation behavior
• Altered degradation kinetics and misleading stability results
• Automatic improvement of drug potency
• Instant crystallization of any drug

Correct Answer: Altered degradation kinetics and misleading stability results

Q29. Which experimental measurement correlates best with the ionic content of a solution and is often used to monitor ionic strength changes?

• Refractometry
• Conductivity measurement
• Fluorescence spectroscopy
• Viscometry

Correct Answer: Conductivity measurement

Q30. Does ionic strength affect the apparent partition coefficient (log P or distribution) of ionizable drugs?

• No, ionic strength has no effect on partitioning
• Yes, it can change apparent partitioning by altering ionization and activity
• Only temperature affects partition coefficient
• Partitioning is fixed by molecular formula and cannot change

Correct Answer: Yes, it can change apparent partitioning by altering ionization and activity