Dissociation constant – determination and applications MCQs With Answer

Dissociation constant – determination and applications MCQs With Answer

Understanding the dissociation constant (Ka) and its logarithmic form (pKa) is essential for B.Pharm students focusing on drug ionization, solubility, and formulation. This introduction covers key concepts such as Ka definition, pKa = -log Ka, Henderson-Hasselbalch equation, fraction ionized, and experimental methods for determination (potentiometry, spectrophotometry, conductometry, NMR, and chromatography). Emphasis is placed on practical applications in drug absorption, pH-dependent solubility, buffer design, salt selection, and pharmacokinetics. Mastering these topics helps predict drug behavior in biological systems and optimize dosage forms. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the chemical definition of the acid dissociation constant (Ka)?

• The equilibrium constant for the reaction HA ⇌ H+ + A− expressed as Ka = [HA]/([H+][A−])
• The equilibrium constant for HA ⇌ H+ + A− expressed as Ka = [H+][A−]/[HA]
• The rate constant for ionization of HA in water
• The pH at which half of HA is dissociated

Correct Answer: The equilibrium constant for HA ⇌ H+ + A− expressed as Ka = [H+][A−]/[HA]

Q2. How is pKa related to Ka?

• pKa = log Ka
• pKa = -log Ka
• pKa = 10^Ka
• pKa = Ka / 2

Correct Answer: pKa = -log Ka

Q3. Which equation directly relates pH, pKa and the ratio of ionized to unionized forms of a monoprotic weak acid?

• Nernst equation
• Henderson-Hasselbalch equation
• Van’t Hoff equation
• Michaelis-Menten equation

Correct Answer: Henderson-Hasselbalch equation

Q4. For a weak acid, at which pH is 50% of the drug ionized?

• pH = pKa
• pH = pKa + 1
• pH = pKa – 1
• pH = pKa + 7

Correct Answer: pH = pKa

Q5. Which experimental method measures pKa by following pH change during titration with a strong base?

• Spectrophotometry
• Potentiometric titration
• Conductometric titration
• NMR titration

Correct Answer: Potentiometric titration

Q6. In potentiometric determination of pKa, which electrode is commonly used to measure pH?

• Calomel electrode
• Glass electrode
• Platinum electrode
• Saturated silver electrode

Correct Answer: Glass electrode

Q7. Which method uses changes in UV-visible absorbance with pH to determine pKa for chromophoric compounds?

• Spectrophotometric method
• Conductometric method
• Potentiometric method
• Chromatographic retention method

Correct Answer: Spectrophotometric method

Q8. What does an isosbestic point in spectrophotometric pH titration indicate?

• Presence of more than two species
• Complete degradation of the drug
• Simple interconversion between two absorbing species
• Instrumental error

Correct Answer: Simple interconversion between two absorbing species

Q9. Which technique estimates pKa by observing changes in chemical shift of nuclei with pH?

• Mass spectrometry
• NMR titration
• Infrared spectroscopy
• Polarimetry

Correct Answer: NMR titration

Q10. In conductometric titration, why does conductivity change near equivalence for weak acid-strong base titration?

• Because ionic strength remains constant
• Because ionic species and mobility change as HA is converted to A− and H+ is neutralized
• Because temperature increases drastically
• Because solvent polarity decreases

Correct Answer: Because ionic species and mobility change as HA is converted to A− and H+ is neutralized

Q11. Which graphical method can be used with potentiometric titration data to determine pKa more accurately?

• Henderson plot
• Gran plot
• Lineweaver-Burk plot
• Scatchard plot

Correct Answer: Gran plot

Q12. For a weak base B, what is the expression for base dissociation constant Kb?

• Kb = [BH+][OH−]/[B]
• Kb = [B][OH−]/[BH+]
• Kb = [BH+]/[B][OH−]
• Kb = [B]/[BH+][OH−]

Correct Answer: Kb = [BH+][OH−]/[B]

Q13. How are pKa and pKb of a conjugate acid-base pair related at 25°C?

• pKa + pKb = 1
• pKa + pKb = pKw (≈14 at 25°C)
• pKa × pKb = pKw
• pKa = pKb

Correct Answer: pKa + pKb = pKw (≈14 at 25°C)

Q14. Which property of a drug is directly affected by its pKa in physiological pH?

• Melting point
• Ionization state and therefore solubility and permeability
• Optical rotation
• Viscosity

Correct Answer: Ionization state and therefore solubility and permeability

Q15. According to the pH partition theory, which form of a drug preferentially permeates lipid membranes?

• Ionized form
• Unionized form
• Both ionized and unionized equally
• Only salt forms

Correct Answer: Unionized form

Q16. When selecting a salt form to improve solubility of a weak base drug, which approach is commonly used?

• Form a salt with a weak acid to produce a more water-soluble salt
• Convert drug to neutral ester
• Form a co-crystal with a non-ionizable solvent
• Avoid any ionic interactions

Correct Answer: Form a salt with a weak acid to produce a more water-soluble salt

Q17. For a weak acid with pKa 4.5, which pH would maximize unionized fraction relevant for passive absorption?

• pH 2.0
• pH 7.4
• pH 5.0
• pH 9.0

Correct Answer: pH 2.0

Q18. Which factor does NOT directly influence the measured Ka in an experimental determination?

• Temperature
• Ionic strength of the medium
• Presence of complexing agents
• Color of the solution

Correct Answer: Color of the solution

Q19. What is the effect of increasing ionic strength on the apparent Ka (activity-based) commonly observed?

• Apparent Ka remains unchanged because activities are constant
• Apparent Ka may change due to altered activity coefficients of ions
• Apparent Ka becomes zero
• Apparent Ka equals concentration-based Ka always

Correct Answer: Apparent Ka may change due to altered activity coefficients of ions

Q20. Which practical formulation decision is guided by drug pKa knowledge?

• Choice of capsule color
• Selection of appropriate pH for liquid formulation to ensure stability and solubility
• Tablet engraving pattern
• Compressibility of placebo

Correct Answer: Selection of appropriate pH for liquid formulation to ensure stability and solubility

Q21. In Henderson-Hasselbalch form for a weak base (BH+ ↔ B + H+), what is the correct relation?

• pH = pKa + log([BH+]/[B])
• pH = pKa + log([B]/[BH+])
• pH = pKa – log([B]/[BH+])
• pH = pKw + log([B]/[BH+])

Correct Answer: pH = pKa + log([B]/[BH+])

Q22. Which method can determine pKa by plotting chromatographic capacity factor (k’) versus pH?

• Mass spectrometry
• Potentiometry
• pH-dependent reverse phase HPLC (chromatographic method)
• Infrared spectroscopy

Correct Answer: pH-dependent reverse phase HPLC (chromatographic method)

Q23. In titration of a weak acid with strong base, the pH at the half-equivalence point equals:

• Equivalence point pH
• pKa of the weak acid
• pKw
• pH = 7 always

Correct Answer: pKa of the weak acid

Q24. Which of the following is a limitation of spectrophotometric pKa determination?

• Requires chromophore with pH-dependent absorbance
• Cannot be automated
• Is insensitive to pH changes
• Works only for salts

Correct Answer: Requires chromophore with pH-dependent absorbance

Q25. What does a very high Ka value indicate about an acid?

• It is a very weak acid
• It is a very strong acid (more dissociation)
• It has no conjugate base
• Its pKa is very large

Correct Answer: It is a very strong acid (more dissociation)

Q26. Which pKa range typically indicates a drug will be partially ionized at physiological pH (7.4)?

• pKa < 1 or > 13 only
• pKa around 4–10
• pKa = 0 only
• pKa exactly 7.4 only

Correct Answer: pKa around 4–10

Q27. How does pKa influence oral drug absorption from stomach vs intestine?

• Drugs with pKa near stomach pH are more unionized in stomach and better absorbed there
• pKa has no effect on absorption across GI tract
• All drugs are best absorbed in stomach regardless of pKa
• Only molecular weight affects absorption

Correct Answer: Drugs with pKa near stomach pH are more unionized in stomach and better absorbed there

Q28. Which technique uses electrophoretic mobility changes vs pH to estimate pKa?

• Capillary electrophoresis
• Gas chromatography
• Polarography
• Size exclusion chromatography

Correct Answer: Capillary electrophoresis

Q29. Why is temperature control important when determining pKa experimentally?

• Temperature does not affect pKa
• Temperature influences dissociation equilibria, altering Ka and pKa values
• Higher temperature always increases pKa to infinity
• Temperature only affects color, not pKa

Correct Answer: Temperature influences dissociation equilibria, altering Ka and pKa values

Q30. For amphoteric compounds (both acidic and basic groups), what parameter is important related to pKa values?

• Molar absorptivity only
• Isoelectric point (pI) determined from pKa values of acidic and basic groups
• Only one pKa matters
• They have no ionizable groups

Correct Answer: Isoelectric point (pI) determined from pKa values of acidic and basic groups

Q31. Which statement about pKa and drug-protein binding is true?

• Ionization state can alter affinity of drug for plasma proteins
• Protein binding is independent of ionization
• Only covalent drugs bind proteins
• Ionized drugs always bind more strongly than unionized

Correct Answer: Ionization state can alter affinity of drug for plasma proteins

Q32. What is the effect of pH on solubility of a weakly basic drug?

• Solubility decreases at low pH
• Solubility increases in acidic media due to protonation
• Solubility independent of pH
• Solubility highest at pH = 14

Correct Answer: Solubility increases in acidic media due to protonation

Q33. Which mathematical form gives fraction ionized (α) for a weak acid at given pH?

• α = 1 / (1 + 10^(pH – pKa))
• α = 1 / (1 + 10^(pKa – pH))
• α = 10^(pH – pKa)
• α = pH × pKa

Correct Answer: α = 1 / (1 + 10^(pH – pKa))

Q34. Which is true about pKa determination by potentiometry for polyprotic acids?

• Only one pKa can be determined
• Multiple pKa values appear as multiple inflection points in the titration curve
• Potentiometry cannot detect polyprotic behavior
• pKa values merge into a single average value

Correct Answer: Multiple pKa values appear as multiple inflection points in the titration curve

Q35. What is a common experimental challenge when determining pKa for very lipophilic drugs?

• They readily dissolve in water making measurement trivial
• Low aqueous solubility complicates achieving required concentrations for analysis
• They always have pKa ≈ 7 making methods redundant
• They show no pH-dependent behavior

Correct Answer: Low aqueous solubility complicates achieving required concentrations for analysis

Q36. Which analytical approach can help determine pKa of poorly soluble compounds?

• Use of cosolvents and extrapolation to zero cosolvent
• Ignore solubility issues and proceed
• Measure at extremely low pH only
• Only theoretical predictions are possible

Correct Answer: Use of cosolvents and extrapolation to zero cosolvent

Q37. Which of the following best describes the impact of pKa on renal excretion of drugs?

• Ionization state affects tubular reabsorption: ionized form is less reabsorbed and more readily excreted
• Only molecular weight controls renal excretion
• Unionized drugs are always excreted faster
• pKa has no role in renal excretion

Correct Answer: Ionization state affects tubular reabsorption: ionized form is less reabsorbed and more readily excreted

Q38. In a mixture showing an isosbestic point, what assumption is most appropriate for pKa analysis?

• More than two species contribute significantly
• Two dominant interconverting species with constant total concentration
• The compound is degraded
• pH measurement is unreliable

Correct Answer: Two dominant interconverting species with constant total concentration

Q39. Which pKa determination method directly measures ionic strength and potential, allowing correction for activity coefficients?

• Spectrophotometry
• Potentiometry
• Ultracentrifugation
• Thin-layer chromatography

Correct Answer: Potentiometry

Q40. What is the relationship between pKa and stability of a drug susceptible to acid hydrolysis?

• Lower pH near pKa always stabilizes the drug
• Stability depends on the dominant chemical species; ionization can increase or decrease hydrolysis rate
• pKa has no impact on hydrolysis
• Only temperature matters for hydrolysis

Correct Answer: Stability depends on the dominant chemical species; ionization can increase or decrease hydrolysis rate

Q41. Which statement about pKa prediction using computational tools is correct?

• Predictions are always exact and replace experiments
• Computational pKa estimates are useful but require experimental validation due to solvation and tautomerism complexities
• Computational methods cannot predict pKa at all
• Predictions only work for inorganic acids

Correct Answer: Computational pKa estimates are useful but require experimental validation due to solvation and tautomerism complexities

Q42. Which of the following is a direct application of pKa in design of controlled-release formulations?

• Determining tablet color
• Selecting pH-dependent polymer coatings to control drug release by ionization state
• Choosing capsule size
• Determining shelf-life only by pKa

Correct Answer: Selecting pH-dependent polymer coatings to control drug release by ionization state

Q43. When a weak acid and its salt are present, how does buffer capacity change near the pKa?

• Buffer capacity is minimal at pKa
• Buffer capacity is maximal near pKa
• Buffer capacity only depends on temperature
• Buffer capacity is zero at pKa

Correct Answer: Buffer capacity is maximal near pKa

Q44. Which of the following best explains why pKa is important for transdermal drug delivery?

• Ionization state affects partitioning into the lipid-rich stratum corneum and hence permeation rate
• Only molecular weight affects transdermal delivery
• pKa controls melting point used for patches
• Transdermal delivery ignores ionization

Correct Answer: Ionization state affects partitioning into the lipid-rich stratum corneum and hence permeation rate

Q45. Which experimental sign suggests inaccurate pKa determination due to CO2 absorption in potentiometric titration?

• Stable baseline pH
• Gradual acidification of the blank over time
• No change in pH during titration
• Immediate sharp endpoints unaffected

Correct Answer: Gradual acidification of the blank over time

Q46. Which of these is true about the effect of solvent polarity on pKa values?

• pKa values are solvent-independent
• Less polar solvents usually shift pKa because solvation of ions changes
• Solvent only affects color
• Solvent always lowers pKa to zero

Correct Answer: Less polar solvents usually shift pKa because solvation of ions changes

Q47. In a clinical context, why might knowledge of a drug’s pKa guide co-administration with antacids or proton pump inhibitors?

• Because pKa tells you pill size
• Because changes in gastric pH can alter ionization, dissolution and absorption of the drug
• Because pKa determines heart rate interactions
• Because pKa indicates drug-protein covalent binding

Correct Answer: Because changes in gastric pH can alter ionization, dissolution and absorption of the drug

Q48. Which method utilizes shifts in mobility in capillary electrophoresis to determine pKa without requiring chromophores?

• UV-Vis spectrophotometry
• Capillary electrophoresis with pH scanning
• Polarimetry
• Fluorescence only

Correct Answer: Capillary electrophoresis with pH scanning

Q49. When a drug has multiple ionizable groups, how are pKa values typically reported?

• Only the lowest pKa is reported
• Each ionizable group has its own pKa (pKa1, pKa2, …), often with microscopic and macroscopic distinctions
• They are averaged into a single value
• pKa does not apply to polyprotic drugs

Correct Answer: Each ionizable group has its own pKa (pKa1, pKa2, …), often with microscopic and macroscopic distinctions

Q50. Which best practice improves accuracy of pKa measurement for weak electrolytes in the lab?

• Neglect ionic strength and temperature control
• Control temperature, ionic strength, use appropriate analytical concentration, and validate with more than one method
• Only run a single measurement at random pH
• Use only computational prediction without experiments

Correct Answer: Control temperature, ionic strength, use appropriate analytical concentration, and validate with more than one method

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com