Introduction: Applications of complexation MCQs With Answer are essential for B. Pharm students preparing for exams and practical formulation work. Complexation in pharmaceutics covers cyclodextrin inclusion complexes, metal chelation, ion-pairing, and complex-mediated drug delivery strategies that improve solubility, stability, bioavailability, and taste masking. This SEO-friendly guide emphasizes pharmaceutical complexation concepts, phase-solubility diagrams, analytical determination of stability constants, and formulation applications. Carefully designed questions with clear answers help reinforce learning for formulation scientists, analytical chemists, and pharmacology trainees. Focused practice on these topics enhances understanding of mechanism, characterization techniques (UV, NMR, DSC, XRD), and real-world formulation problems. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is the primary purpose of forming a cyclodextrin inclusion complex with a drug?
- Increase melting point of the drug
- Enhance solubility and bioavailability of the drug
- Convert a drug into a gas
- Reduce molecular weight of the drug
Correct Answer: Enhance solubility and bioavailability of the drug
Q2. Which method is commonly used to determine the stoichiometry of a drug–complex using varying mole fractions?
- Higuchi-Connors plot
- Job’s method (method of continuous variations)
- Benesi-Hildebrand plot
- Van’t Hoff analysis
Correct Answer: Job’s method (method of continuous variations)
Q3. In complexation, the formation (stability) constant Kf is defined as?
- [Complex]/([Ligand]+[Metal])
- [Complex]/([Metal][Ligand])
- [Metal][Ligand]/[Complex]
- [Complex] × [Metal][Ligand]
Correct Answer: [Complex]/([Metal][Ligand])
Q4. Which analytical technique provides information about molecular interactions and hydrogen bonding in drug complexes?
- Thermogravimetric analysis (TGA)
- Fourier-transform infrared spectroscopy (FTIR)
- Atomic absorption spectroscopy (AAS)
- Gel electrophoresis
Correct Answer: Fourier-transform infrared spectroscopy (FTIR)
Q5. A-type phase-solubility diagram of a drug-cyclodextrin system indicates:
- No complex formation
- Precipitation of drug
- Linear increase in drug solubility with cyclodextrin concentration
- Formation of a complex with decreasing solubility
Correct Answer: Linear increase in drug solubility with cyclodextrin concentration
Q6. Which cyclodextrin derivative is commonly used to improve aqueous solubility of hydrophobic drugs?
- α-Cyclodextrin
- β-Cyclodextrin
- Hydroxypropyl-β-cyclodextrin (HP-β-CD)
- γ-Cyclodextrin only
Correct Answer: Hydroxypropyl-β-cyclodextrin (HP-β-CD)
Q7. Complexometric titration with EDTA is typically used to estimate which ions in pharmaceutical analysis?
- Sodium and potassium
- Calcium and magnesium
- Chloride and bromide
- Phosphate and sulfate
Correct Answer: Calcium and magnesium
Q8. In Benesi-Hildebrand analysis for a 1:1 complex, the reciprocal of measured signal versus reciprocal of ligand concentration yields:
- A straight line to determine the formation constant
- A parabolic curve indicating no complex
- Temperature dependence only
- Direct measurement of molecular weight
Correct Answer: A straight line to determine the formation constant
Q9. Which parameter most directly reflects the strength of a drug–ligand complex?
- Melting point
- Formation (stability) constant, Kf
- Color of solution
- Viscosity
Correct Answer: Formation (stability) constant, Kf
Q10. Ion-pair complexation is primarily used in pharmaceutics to:
- Increase drug volatility
- Enhance partitioning into organic phases for extraction or permeation
- Decrease drug potency
- Convert drugs into polymers
Correct Answer: Enhance partitioning into organic phases for extraction or permeation
Q11. Which factor does NOT significantly influence complex formation between a drug and cyclodextrin?
- pH of the medium
- Temperature
- Drug’s intestinal permeability only
- Ionic strength
Correct Answer: Drug’s intestinal permeability only
Q12. EDTA acts as a chelating agent because it provides:
- Only one donor atom
- Multiple donor atoms to bind a metal ion (multidentate ligand)
- Hydrophobic cavity for inclusion
- Polymeric crosslinking
Correct Answer: Multiple donor atoms to bind a metal ion (multidentate ligand)
Q13. A 1:2 drug:cyclodextrin complex stoichiometry indicates:
- One drug molecule binds to two cyclodextrin molecules
- Two drugs bind to one cyclodextrin
- No complex formation
- Drug decomposes in presence of cyclodextrin
Correct Answer: One drug molecule binds to two cyclodextrin molecules
Q14. Which instrumental technique can confirm the crystalline to amorphous transition upon complexation?
- UV-Visible spectroscopy
- X-ray powder diffraction (XRPD)
- pH meter
- Conductivity meter
Correct Answer: X-ray powder diffraction (XRPD)
Q15. Complexation is used in taste masking because:
- It increases drug bitterness
- It prevents drug contact with taste receptors by encapsulation
- It digests the drug in the mouth
- It removes all drug activity
Correct Answer: It prevents drug contact with taste receptors by encapsulation
Q16. Which is a common method to prepare cyclodextrin inclusion complexes?
- Solvent evaporation
- Cold chain lyophilization only
- Polymerization
- Centrifugation without solvent
Correct Answer: Solvent evaporation
Q17. In phase-solubility studies, an AL-type diagram suggests what complex stoichiometry?
- 1:1 complex stoichiometry
- No complexation
- 1:2 complex stoichiometry only
- Complex decomposition
Correct Answer: 1:1 complex stoichiometry
Q18. Which thermodynamic parameter indicates whether complexation is spontaneous?
- ΔH only
- ΔS only
- ΔG (Gibbs free energy change)
- Activation energy
Correct Answer: ΔG (Gibbs free energy change)
Q19. Metal complexation in formulations can prevent rancidity by chelating:
- Trace metal ions that catalyze oxidation
- Only organic acids
- Water molecules
- Enzymes permanently
Correct Answer: Trace metal ions that catalyze oxidation
Q20. Which of the following is NOT typically used to characterize drug–cyclodextrin complexes?
- Differential scanning calorimetry (DSC)
- Nuclear magnetic resonance (NMR)
- Mass spectrometry for intact complex in bulk formulations
- Scanning electron microscopy (SEM)
Correct Answer: Mass spectrometry for intact complex in bulk formulations
Q21. In an inclusion complex, the guest molecule is typically located:
- On the external surface of the host only
- Within the hydrophobic cavity of the host
- In the aqueous phase completely
- As a covalent adduct with the host
Correct Answer: Within the hydrophobic cavity of the host
Q22. A high formation constant (Kf) for a drug–cyclodextrin complex implies:
- Weak binding and rapid dissociation
- Strong binding and more stable complex
- Complete chemical reaction to form a new compound
- No effect on drug solubility
Correct Answer: Strong binding and more stable complex
Q23. Complexation can increase drug chemical stability by:
- Exposing labile groups to solvent
- Shielding labile functional groups from degradative agents
- Reducing molecular weight
- Increasing pH only
Correct Answer: Shielding labile functional groups from degradative agents
Q24. Which equation relates absorbance changes to complex formation for spectrophotometric determination?
- Beer’s law with formation constant adjustments
- Henderson-Hasselbalch equation
- Arrhenius equation
- Nernst equation
Correct Answer: Beer’s law with formation constant adjustments
Q25. The continuous variation (Job’s) plot shows a maximum at a mole fraction of 0.5 indicating:
- 2:1 stoichiometry
- 1:1 stoichiometry
- No complex formation
- 3:1 stoichiometry
Correct Answer: 1:1 stoichiometry
Q26. Which ligand property enhances formation of chelate complexes with metals?
- Monodentate nature
- Polydentate ability to form ring structures with metal
- High volatility
- Hydrophobicity only
Correct Answer: Polydentate ability to form ring structures with metal
Q27. Which complexation approach is useful to enhance transdermal permeation of ionized drugs?
- Inclusion complex with cyclodextrin only
- Ion-pair complexation to increase lipophilicity
- Covalent modification to large polymers
- Freeze-drying without excipients
Correct Answer: Ion-pair complexation to increase lipophilicity
Q28. Which factor can cause a decrease in apparent stability constant in a complexation study?
- Decrease in temperature for exothermic complexation
- Use of organic cosolvent that competes with binding
- Increasing ionic strength always increases Kf
- Increasing host concentration
Correct Answer: Use of organic cosolvent that competes with binding
Q29. Which pharmaceutical application uses metal complexation to remove toxic metal residues?
- Use of cyclodextrins to remove bacteria
- Chelation therapy using agents like EDTA or DTPA
- Ion exchange resins for taste masking only
- Polymer encapsulation for sustained release
Correct Answer: Chelation therapy using agents like EDTA or DTPA
Q30. Inclusion complex formation is mainly driven by which interactions?
- Strong covalent bonds only
- Non-covalent interactions such as van der Waals, hydrophobic and hydrogen bonding
- Nuclear forces
- Electrostatic repulsion only
Correct Answer: Non-covalent interactions such as van der Waals, hydrophobic and hydrogen bonding
Q31. Which experimental technique can provide direct evidence of guest orientation inside cyclodextrin cavity?
- UV-Vis absorption only
- 1H-NMR (chemical shift changes)
- Colorimetry
- pH titration
Correct Answer: 1H-NMR (chemical shift changes)
Q32. In competitive complexation, a stronger ligand will:
- Be displaced more easily by weaker ligands
- Displace a weaker ligand from the metal complex
- Have no effect on equilibrium
- Always precipitate out
Correct Answer: Displace a weaker ligand from the metal complex
Q33. Which is a limitation of cyclodextrin complexation in parenteral formulations?
- Complete elimination of all side effects
- Potential nephrotoxicity at high cyclodextrin concentrations
- Unlimited solubilization capacity
- Instant chemical reaction to form new drug
Correct Answer: Potential nephrotoxicity at high cyclodextrin concentrations
Q34. When conducting a phase-solubility study, the slope of the linear portion can be used to:
- Calculate melting point
- Estimate the apparent stability constant (K1:1)
- Determine color intensity
- Measure viscosity
Correct Answer: Estimate the apparent stability constant (K1:1)
Q35. Which outcome suggests the formation of an inclusion complex after DSC analysis?
- Discrete melting peak of pure drug remains unchanged
- Disappearance or broadening of the drug melting endotherm
- Increase in enthalpy corresponding to polymerization
- Appearance of a new gas evolution peak
Correct Answer: Disappearance or broadening of the drug melting endotherm
Q36. Complex formation that enhances drug permeability through biological membranes is most commonly due to:
- Reduction of drug partition coefficient
- Increase in drug lipophilicity or masking ionization via ion-pairing
- Increasing molecular size beyond membrane limits
- Complete removal of drug from solution
Correct Answer: Increase in drug lipophilicity or masking ionization via ion-pairing
Q37. Which descriptor best defines a chelate effect?
- Decreased stability of polydentate ligand complexes
- Enhanced stability of complexes formed by multidentate ligands compared to equivalent monodentate ligands
- Formation of complexes that are always insoluble
- Reduction in reaction rate only
Correct Answer: Enhanced stability of complexes formed by multidentate ligands compared to equivalent monodentate ligands
Q38. Which is true about the kinetics of complex formation in most pharmaceutical systems?
- Complexation reactions are always instantaneous
- Rate can vary; some complexes form rapidly while others require time or heating
- Complexation always requires enzymatic catalysis
- Complexation is impossible in aqueous media
Correct Answer: Rate can vary; some complexes form rapidly while others require time or heating
Q39. Which pharmaceutical application uses cyclodextrin complexes to stabilize volatile or photosensitive drugs?
- Only for parenteral contamination control
- Formulation of ophthalmic, topical, and oral dosage forms to protect from degradation
- To increase volatility for inhalation only
- To intentionally degrade drugs faster
Correct Answer: Formulation of ophthalmic, topical, and oral dosage forms to protect from degradation
Q40. What is the effect of complexation on drug dissolution rate?
- Always decreases dissolution rate
- Can increase apparent dissolution rate by improving solubility and wettability
- Has no effect on dissolution
- Always causes immediate precipitation
Correct Answer: Can increase apparent dissolution rate by improving solubility and wettability
Q41. Which is a typical indicator used in complexometric titration with EDTA for calcium quantification?
- Phenolphthalein
- Eriochrome Black T
- Methylene blue
- Bromothymol blue
Correct Answer: Eriochrome Black T
Q42. In a drug–metal complex, inner-sphere coordination involves:
- Indirect interaction through water molecules only
- Direct bonding between ligand donor atom and metal ion
- Only electrostatic attraction with no bonding
- Peptide bond formation
Correct Answer: Direct bonding between ligand donor atom and metal ion
Q43. Which of the following enhances competitive displacement in a mixture of ligands?
- Higher ligand concentration and greater binding affinity
- Lower temperature always
- Absence of solvent
- Reducing ionic strength to zero
Correct Answer: Higher ligand concentration and greater binding affinity
Q44. Which characterization technique can detect changes in surface morphology after complex formation?
- Infrared spectroscopy only
- Scanning electron microscopy (SEM)
- Polarimetry
- Conductivity measurement
Correct Answer: Scanning electron microscopy (SEM)
Q45. Which statement about ion-pair complexes used in liquid-liquid extraction is correct?
- Ion-pairing decreases extraction into organic solvents
- Neutral ion-pairs partition more readily into organic solvents improving extraction
- Ion-pairs only form in solid state
- Ion-pairing always produces covalent compounds
Correct Answer: Neutral ion-pairs partition more readily into organic solvents improving extraction
Q46. Which descriptor applies to DTPA compared to EDTA in chelation therapy?
- DTPA has fewer donor atoms than EDTA
- DTPA is often more effective for certain radioactive metal chelation due to different binding geometry
- DTPA is not used medically
- DTPA always forms insoluble complexes
Correct Answer: DTPA is often more effective for certain radioactive metal chelation due to different binding geometry
Q47. Which observation during UV-Vis titration suggests complex formation?
- No change in absorbance at any wavelength
- Shifts in λmax or change in absorbance intensity on addition of complexing agent
- Immediate precipitation in all cases
- Complete disappearance of solvent peak only
Correct Answer: Shifts in λmax or change in absorbance intensity on addition of complexing agent
Q48. For a drug with low aqueous solubility, which formulation strategy involving complexation is most appropriate?
- Form a non-specific polymer blend only
- Prepare an inclusion complex with cyclodextrin to improve solubility
- Always convert it to a gas
- None; complexation never helps solubility
Correct Answer: Prepare an inclusion complex with cyclodextrin to improve solubility
Q49. Which effect can cosolvents (ethanol) have on host–guest complexation?
- Enhance complexation by removing competing water interactions
- Never affect complexation
- Always convert host to monomeric form
- Only increase melting point
Correct Answer: Enhance complexation by removing competing water interactions
Q50. In designing MCQs on complexation for B. Pharm students, the most important learning outcome is to ensure students can:
- Memorize all formation constants without understanding context
- Understand mechanisms, characterize complexes, and apply complexation to solve formulation and analytical problems
- Avoid using instrumentation
- Only focus on theoretical math with no application
Correct Answer: Understand mechanisms, characterize complexes, and apply complexation to solve formulation and analytical problems

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