Experimental determination of physicochemical parameters MCQs With Answer

Introduction: Experimental determination of physicochemical parameters is essential for B.Pharm students to understand drug behavior, formulation design, and quality control. This topic covers methods to measure solubility, partition coefficient (log P), pH, melting point, boiling point, refractive index, density, viscosity, surface tension, osmolarity, and water content (Karl Fischer). It also includes instrumental techniques such as DSC, TGA, refractometry, viscometry, and conductivity, plus calibration, sample preparation, and common experimental errors. Mastery of these parameters supports formulation optimization, stability assessment, and regulatory compliance. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the most appropriate experimental method to determine the octanol–water partition coefficient (log P) of a neutral drug?

  • Shake-flask method with HPLC analysis
  • Potentiometric titration
  • Karl Fischer titration
  • UV melting point method

Correct Answer: Shake-flask method with HPLC analysis

Q2. Which technique directly measures the amount of water in a sample with high accuracy for low moisture contents?

  • Loss on drying (oven drying)
  • Karl Fischer titration
  • Gravimetric ash analysis
  • Refractive index measurement

Correct Answer: Karl Fischer titration

Q3. Which physicochemical parameter is primarily determined using a Brookfield viscometer?

  • Surface tension
  • Intrinsic viscosity
  • Absolute viscosity (viscosity of a fluid)
  • True density

Correct Answer: Absolute viscosity (viscosity of a fluid)

Q4. Why is pH measurement important for drug solubility studies?

  • Because pH changes melting point
  • Because pH affects ionization and thus solubility of ionizable drugs
  • Because pH determines the refractive index
  • Because pH controls viscosity directly

Correct Answer: Because pH affects ionization and thus solubility of ionizable drugs

Q5. Which instrument is best suited to determine thermal transitions such as glass transition and melting point precisely?

  • Differential Scanning Calorimetry (DSC)
  • UV-Vis spectrophotometer
  • Refractometer
  • Ostwald viscometer

Correct Answer: Differential Scanning Calorimetry (DSC)

Q6. In the shake-flask log P determination, what is a common source of error that must be minimized?

  • Using ultrapure solvents
  • Incomplete phase separation and emulsion formation
  • Excessive stirring speed improving equilibrium
  • Using analytical detection methods

Correct Answer: Incomplete phase separation and emulsion formation

Q7. Which parameter is measured by a refractometer?

  • pH
  • Refractive index
  • Osmolarity
  • Viscosity

Correct Answer: Refractive index

Q8. For conductivity measurements of aqueous pharmaceutical solutions, conductivity is most strongly influenced by:

  • Presence of nonionic solutes
  • Ionic strength and type of ions present
  • Viscosity of the solution only
  • Temperature only, independent of ionic content

Correct Answer: Ionic strength and type of ions present

Q9. Which method is suitable to determine the dissolution rate of a solid oral dosage form?

  • USP paddle or basket dissolution test with UV/HPLC sampling
  • Karl Fischer titration
  • Capillary melting point apparatus
  • Refractive index measurement

Correct Answer: USP paddle or basket dissolution test with UV/HPLC sampling

Q10. Intrinsic viscosity [η] of a polymer is obtained from experimental viscosity measurements by extrapolating which quantity to zero concentration?

  • Relative density
  • Reduced viscosity or inherent viscosity
  • Specific gravity
  • Surface tension

Correct Answer: Reduced viscosity or inherent viscosity

Q11. Which of the following correctly relates melting point determination by capillary method?

  • It provides quantitative purity data for volatile liquids
  • Impurities generally depress and broaden the melting point range
  • Impurities increase the melting point sharply
  • It measures boiling behavior

Correct Answer: Impurities generally depress and broaden the melting point range

Q12. What is the main advantage of DSC over simple capillary melting point methods?

  • DSC cannot measure melting points accurately
  • DSC provides quantitative heat flow and precise transition temperatures and enthalpies
  • DSC only measures refractive index changes
  • DSC is slower and less sensitive

Correct Answer: DSC provides quantitative heat flow and precise transition temperatures and enthalpies

Q13. Which physicochemical test assesses the total amount of inorganic residues in a drug substance after ignition?

  • Loss on drying
  • Ash value
  • pKa determination
  • Partition coefficient

Correct Answer: Ash value

Q14. Which statement about loss on drying (LOD) versus Karl Fischer (KF) is true?

  • LOD is always more accurate than KF for trace water
  • KF specifically measures water while LOD may remove volatile solvents or degrade sample
  • KF measures volatile organics better than LOD
  • LOD can differentiate bound and free water reliably

Correct Answer: KF specifically measures water while LOD may remove volatile solvents or degrade sample

Q15. Which unit is commonly used to express viscosity in Brookfield viscometer readings?

  • mL
  • Pascal-second (Pa·s) or centipoise (cP)
  • mol/L
  • g/cm3

Correct Answer: Pascal-second (Pa·s) or centipoise (cP)

Q16. The Ostwald viscometer measures kinematic viscosity; kinematic viscosity equals:

  • Dynamic viscosity × density
  • Dynamic viscosity / density
  • Surface tension / density
  • Density / dynamic viscosity

Correct Answer: Dynamic viscosity / density

Q17. When determining pKa potentiometrically, which curve is analyzed to find the pKa?

  • Conductivity vs temperature curve
  • Titration (pH vs volume of titrant) curve, finding midpoint of buffering region
  • Refractive index vs concentration curve
  • Viscosity vs shear rate curve

Correct Answer: Titration (pH vs volume of titrant) curve, finding midpoint of buffering region

Q18. Surface tension measurements in formulation studies are important because surface tension affects:

  • Color of the formulation
  • Wettability, spreading, and emulsion stability
  • Melting point only
  • Partition coefficient directly

Correct Answer: Wettability, spreading, and emulsion stability

Q19. Which method is commonly used for accurate density measurements of liquids in pharmaceutical labs?

  • Pycnometer
  • pH meter
  • UV spectrophotometer
  • Capillary melting point apparatus

Correct Answer: Pycnometer

Q20. In log P measurements for ionizable compounds, what is the partition coefficient usually dependent on?

  • Only on temperature, not pH
  • pH because ionization state affects partitioning between octanol and water
  • Only on ionic strength of octanol
  • On refractive index of water

Correct Answer: pH because ionization state affects partitioning between octanol and water

Q21. Which analytical technique helps identify functional groups and assess drug–excipient compatibility through interaction studies?

  • FTIR spectroscopy
  • Ostwald viscometry
  • Pycnometry
  • Conductivity meter

Correct Answer: FTIR spectroscopy

Q22. For accurate pH meter calibration, which practice is essential?

  • Calibrating with at least two standard buffers that bracket the expected sample pH and performing temperature compensation
  • Calibrating only once at the start of the year
  • Using distilled water as a calibration standard
  • Calibrating with organic solvents

Correct Answer: Calibrating with at least two standard buffers that bracket the expected sample pH and performing temperature compensation

Q23. Which parameter gives a quick estimate of ionic strength and dissociation in a solution and is often measured for electrolyte formulations?

  • Surface tension
  • Conductivity
  • Refractive index
  • Viscosity

Correct Answer: Conductivity

Q24. Which experimental method helps determine the true density of a powdered drug?

  • Tap density apparatus only
  • Helium pycnometry or gas pycnometer
  • Ostwald viscometer
  • Refractometer

Correct Answer: Helium pycnometry or gas pycnometer

Q25. When measuring solubility experimentally, why is it important to ensure equilibrium has been reached?

  • Equilibrium prevents partitioning
  • Without equilibrium, measured concentration may reflect kinetic effects, not true solubility
  • Equilibrium increases pH automatically
  • Equilibrium reduces viscosity artifacts

Correct Answer: Without equilibrium, measured concentration may reflect kinetic effects, not true solubility

Q26. Osmolarity of an isotonic ophthalmic solution should be approximately:

  • 50 mOsm/L
  • ~300 mOsm/L (close to physiological osmolarity)
  • 1000 mOsm/L
  • 0 mOsm/L

Correct Answer: ~300 mOsm/L (close to physiological osmolarity)

Q27. Which experimental approach is typically used to determine the surface pKa (apparent pKa) affecting partitioning of amphoteric drugs?

  • Shake-flask log P at multiple pH values with pH-controlled aqueous phase
  • Loss on drying
  • Refractive index measurement at single pH
  • DSC melting point scan only

Correct Answer: Shake-flask log P at multiple pH values with pH-controlled aqueous phase

Q28. In refractometry, why is temperature control important when measuring refractive index of solutions?

  • Temperature has negligible effect
  • Refractive index strongly depends on temperature; uncontrolled temperature yields inaccurate results
  • Temperature only affects color, not refractive index
  • Temperature only affects ionic strength

Correct Answer: Refractive index strongly depends on temperature; uncontrolled temperature yields inaccurate results

Q29. Which of the following best describes an advantage of using HPLC to quantify drug concentration in partition or solubility studies?

  • HPLC is qualitative only, not quantitative
  • HPLC provides high specificity, sensitivity, and separation from impurities and excipients
  • HPLC requires no calibration
  • HPLC cannot separate closely related impurities

Correct Answer: HPLC provides high specificity, sensitivity, and separation from impurities and excipients

Q30. When reporting physicochemical parameter results for regulatory submissions, which practice is essential?

  • Provide only raw instrument files without method description
  • Provide validated methods, calibration data, conditions, and uncertainty/precision metrics
  • Report single measurement only
  • Avoid specifying instrument model or calibration status

Correct Answer: Provide validated methods, calibration data, conditions, and uncertainty/precision metrics

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