Physical incompatibilities – examples and solutions MCQs With Answer

Physical incompatibilities in pharmaceutical formulations refer to undesirable physical changes—such as precipitation, phase separation, caking, or crystallization—occurring between drug substances and excipients. For B. Pharm students, understanding common examples (e.g., pH-induced precipitation, polymorphic transitions, hygroscopicity, deliquescence, adsorption to containers) and practical solutions (buffers, co-solvents, surfactants, particle-size reduction, lyophilization, suitable packaging) is essential for robust formulation design and stability. This topic links theory with hands-on problem solving: predicting incompatibilities, performing compatibility tests, and selecting corrective strategies to ensure safety, efficacy, and manufacturability. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which physical incompatibility is most likely when a drug with low water solubility is mixed with an aqueous buffer that shifts pH to its unionized form?

• Phase separation
• Precipitation
• Adsorption to container surface
• Caking

Correct Answer: Precipitation

Q2. Which excipient is most commonly used to improve wetting and reduce surface adsorption of hydrophobic drug particles in suspensions?

• Buffer salts
• Surfactants (wetting agents)
• Antioxidants
• Preservatives

Correct Answer: Surfactants (wetting agents)

Q3. Deliquescence describes which of the following processes?

• Drug converting between polymorphs
• Solid absorbing moisture and becoming liquid
• Formation of insoluble complex with metal ions
• Gas evolution on mixing

Correct Answer: Solid absorbing moisture and becoming liquid

Q4. Which method helps prevent crystallization of an amorphous drug in a solid dispersion?

• Increasing humidity exposure
• Adding a polymeric stabilizer
• Storing at elevated temperature
• Grinding to larger particle size

Correct Answer: Adding a polymeric stabilizer

Q5. Which physical incompatibility is primarily concerned with the drug changing its crystal form, affecting solubility and bioavailability?

• Polymorphism
• Phase separation
• Foaming
• Oxidation

Correct Answer: Polymorphism

Q6. Which approach is best to prevent phase separation in oil-in-water emulsions?

• Removing surfactants
• Adding an appropriate emulsifier to stabilize the interfacial film
• Increasing the dispersed phase volume beyond 80%
• Using pure water at low temperature

Correct Answer: Adding an appropriate emulsifier to stabilize the interfacial film

Q7. Adsorption of drug to glass or container surfaces can be minimized by:

• Using higher drug concentration only
• Changing container material or adding surfactants
• Storing at high humidity
• Increasing particle size

Correct Answer: Changing container material or adding surfactants

Q8. Which property of excipients most influences caking of powders during storage?

• Thermal conductivity
• Hygroscopicity and moisture uptake
• Optical clarity
• Viscosity in solution

Correct Answer: Hygroscopicity and moisture uptake

Q9. What is a practical solution to prevent pH-induced precipitation of a weakly basic drug in an aqueous formulation?

• Remove buffer and leave pH uncontrolled
• Use an appropriate buffer to keep drug ionized or add co-solvent
• Increase ionic strength without pH control
• Expose to light to increase solubility

Correct Answer: Use an appropriate buffer to keep drug ionized or add co-solvent

Q10. Which test is commonly performed to detect physical incompatibilities between drug and excipients?

• Chemical assay only
• Differential scanning calorimetry (DSC) and visual observation
• Only microbial testing
• pH paper alone

Correct Answer: Differential scanning calorimetry (DSC) and visual observation

Q11. In suspensions, flocculation is often desirable because it:

• Leads to hard cake formation
• Produces loose aggregates that are easily redispersed
• Increases solubility drastically
• Causes irreversible compaction

Correct Answer: Produces loose aggregates that are easily redispersed

Q12. Which technique reduces particle aggregation and improves uniformity in powder blends to avoid segregation?

• Using widely different particle sizes
• Particle size reduction and controlled distribution
• Increasing static charge intentionally
• Avoiding any mixing

Correct Answer: Particle size reduction and controlled distribution

Q13. A drug forms an insoluble complex with divalent metal ions in formulation. Best preventive measure is:

• Adding metal ions to excess
• Include a chelating agent like EDTA or use metal-free water
• Increase temperature to dissolve complex
• Use glass containers to supply metal ions

Correct Answer: Include a chelating agent like EDTA or use metal-free water

Q14. Which strategy helps maintain emulsion stability against creaming?

• Reduce viscosity of continuous phase
• Increase droplet size
• Use suitable emulsifier and increase continuous phase viscosity
• Remove surfactant

Correct Answer: Use suitable emulsifier and increase continuous phase viscosity

Q15. Light-induced physical changes in photosensitive drugs (e.g., color changes) are best managed by:

• Transparent packaging
• Opaque or amber packaging and light-protective additives
• Increasing exposure to sunlight
• Removing antioxidants

Correct Answer: Opaque or amber packaging and light-protective additives

Q16. Which of the following reduces foaming problems in liquid formulations?

• Addition of antifoaming agents like simethicone
• Adding more surfactant with high foaming tendency
• Shaking vigorously before filling
• Using rough container surfaces

Correct Answer: Addition of antifoaming agents like simethicone

Q17. Thermal incompatibility causing recrystallization during storage can be minimized by:

• Storing at uncontrolled fluctuating temperatures
• Optimizing storage temperature and using stabilizing excipients
• Increasing residual solvents intentionally
• Using metal containers that conduct heat

Correct Answer: Optimizing storage temperature and using stabilizing excipients

Q18. Which parameter is most relevant when selecting a co-solvent to enhance solubility and avoid precipitation?

• Co-solvent taste only
• Solubility parameter and miscibility with water
• Color of co-solvent
• Market price exclusively

Correct Answer: Solubility parameter and miscibility with water

Q19. Why is lyophilization used to prevent physical incompatibilities in parenteral formulations?

• It increases the water content permanently
• Removes water to stabilize labile solids and prevent hydrolytic changes
• Creates larger crystals intentionally
• Makes solutions more prone to precipitation

Correct Answer: Removes water to stabilize labile solids and prevent hydrolytic changes

Q20. Which phenomenon describes separation of immiscible liquids into distinct layers over time?

• Polymorphism
• Phase separation
• Hygroscopicity
• Crystallization inhibition

Correct Answer: Phase separation

Q21. Which excipient class is commonly used to reduce caking in powder formulations?

• Diluents with high hygroscopicity
• Anti-caking agents like silica or magnesium stearate
• Strong acids
• Proteolytic enzymes

Correct Answer: Anti-caking agents like silica or magnesium stearate

Q22. What is a common physical incompatibility observed when two ionic drugs of opposite charge are mixed?

• Enhanced solubility
• Complexation or precipitation due to ion pairing
• Complete chemical degradation
• No interaction at all

Correct Answer: Complexation or precipitation due to ion pairing

Q23. To prevent adsorption of peptide drugs to vial surfaces, formulators often:

• Use larger vials without surface treatment
• Add surfactants (e.g., polysorbate 80) or use coated containers
• Store peptides at high pH only
• Aggressively shake before storage

Correct Answer: Add surfactants (e.g., polysorbate 80) or use coated containers

Q24. Which physical test would detect recrystallization of an amorphous drug in a solid dosage form?

• UV-visible spectroscopy of a dilute solution only
• X-ray powder diffraction (XRPD)
• Color match test
• Odor assessment

Correct Answer: X-ray powder diffraction (XRPD)

Q25. In suspensions, increasing viscosity of the continuous phase primarily helps to:

• Promote rapid sedimentation
• Reduce sedimentation rate and help suspend particles
• Increase drug chemical degradation
• Enhance particle aggregation permanently

Correct Answer: Reduce sedimentation rate and help suspend particles

Q26. Which approach can prevent incompatibility caused by eutectic formation between two solids?

• Maintain them in close contact in the same layer
• Use physical barriers or different granulation layers in tablet design
• Increase compression force to form a single phase
• Store at high humidity to homogenize

Correct Answer: Use physical barriers or different granulation layers in tablet design

Q27. A preservative loses effectiveness due to binding with excipients. Best corrective action is:

• Remove preservative entirely
• Screen excipient compatibility and choose non-binding alternatives or adjust preservative type
• Reduce preservative concentration
• Increase storage temperature

Correct Answer: Screen excipient compatibility and choose non-binding alternatives or adjust preservative type

Q28. Which is an example of mechanical physical incompatibility during manufacturing?

• Drug hydrolysis in solution
• Segregation of powder blend during transport
• pH-induced precipitation
• Chemical oxidation

Correct Answer: Segregation of powder blend during transport

Q29. To minimize polymorphic conversion during compression, formulators may:

• Apply uncontrolled high compression speeds only
• Control compression force, use lubricants, and select stable polymorphs
• Introduce moisture during compression
• Aggressively heat the powder bed

Correct Answer: Control compression force, use lubricants, and select stable polymorphs

Q30. Which analytical technique helps monitor particle-size changes that can indicate physical incompatibility in suspensions?

• Gas chromatography
• Laser diffraction or dynamic light scattering
• Polarimetry
• pH strip

Correct Answer: Laser diffraction or dynamic light scattering

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