Pharmaceutical incompatibilities – definition and classification MCQs With Answer

Pharmaceutical incompatibilities occur when drug and excipient components interact to cause undesirable changes in a formulation’s stability, safety, or efficacy. For B. Pharm students, understanding the definition, classification, mechanisms, and prevention of incompatibilities is vital in dispensing, compounding, and product development. Key types include physical incompatibilities (precipitation, liquefaction, sorption), chemical incompatibilities (hydrolysis, oxidation, complexation), and therapeutic incompatibilities (pharmacodynamic/pharmacokinetic interactions). Factors such as pH, temperature, ionic strength, solvents, packaging materials, and order of mixing critically influence compatibility. Prevention relies on buffering, chelation, antioxidants, co-solvents, excipient selection, protective packaging, and evidence-based compatibility references. This foundation helps avoid IV admixture errors, TPN precipitation, and dosage form failures. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the best definition of pharmaceutical incompatibility?

• An unpredictable variability in patient response to a drug
• An undesirable interaction between formulation components leading to physical, chemical, or therapeutic changes
• A regulatory non-compliance during manufacturing
• A bioequivalence failure of a generic product

Correct Answer: An undesirable interaction between formulation components leading to physical, chemical, or therapeutic changes

Q2. Which is the standard classification of pharmaceutical incompatibilities?

• Physical, chemical, and therapeutic
• Mechanistic, kinetic, and dynamic
• Acidic, basic, and neutral
• Immediate, delayed, and cumulative

Correct Answer: Physical, chemical, and therapeutic

Q3. Mixing calcium salts with phosphate in IV fluids mainly risks which incompatibility?

• Therapeutic antagonism
• Physical precipitation
• Enzymatic degradation
• Microbial contamination

Correct Answer: Physical precipitation

Q4. Hydrolysis of aspirin in an alkaline medium is an example of:

• Physical incompatibility
• Chemical incompatibility
• Therapeutic incompatibility
• Packaging incompatibility

Correct Answer: Chemical incompatibility

Q5. Reduced absorption of tetracycline when given with antacids is best classified as:

• Physical incompatibility
• Chemical incompatibility
• Therapeutic incompatibility
• Pharmacogenetic variation

Correct Answer: Therapeutic incompatibility

Q6. Precipitation of a weak base from solution is most likely when the pH is:

• Very low, increasing ionization
• Near its pKa
• Raised, decreasing ionization and solubility
• Buffered strongly with phosphate

Correct Answer: Raised, decreasing ionization and solubility

Q7. A common cause of precipitation when diluting co-solvent injections (e.g., diazepam) with saline is:

• Common ion effect
• Decrease in solvent strength leading to reduced solubility
• Increase in ionic strength increasing solubility
• Formation of micelles

Correct Answer: Decrease in solvent strength leading to reduced solubility

Q8. Nitroglycerin loss from solution stored in PVC containers primarily occurs due to:

• Hydrolytic degradation
• Oxidation by dissolved oxygen
• Adsorption/absorption into the plastic
• Photolytic cleavage

Correct Answer: Adsorption/absorption into the plastic

Q9. Which drug is notably photosensitive and requires light-protective packaging?

• Riboflavin
• Paracetamol
• Metformin
• Atenolol

Correct Answer: Riboflavin

Q10. Which strategy best minimizes oxidative incompatibilities in aqueous formulations?

• Using strong bases to increase pH
• Adding sodium metabisulfite or EDTA and purging with nitrogen
• Replacing water with ethanol
• Storing at high temperature

Correct Answer: Adding sodium metabisulfite or EDTA and purging with nitrogen

Q11. Aspirin tablets commonly undergo which reaction during improper storage?

• Maillard reaction
• Hydrolysis to salicylic acid and acetic acid
• Esterification
• Nitration

Correct Answer: Hydrolysis to salicylic acid and acetic acid

Q12. Liquefaction when triturating camphor with menthol is due to:

• Deliquescence
• Eutectic mixture formation
• Efflorescence
• Polymorphic transition

Correct Answer: Eutectic mixture formation

Q13. Which pair best illustrates efflorescence and deliquescence, respectively?

• Sodium carbonate decahydrate; calcium chloride
• Calcium chloride; sodium carbonate decahydrate
• Sucrose; lactose
• Menthol; thymol

Correct Answer: Sodium carbonate decahydrate; calcium chloride

Q14. “Salting-out” refers to:

• Increased solubility of nonionic solutes with added salts
• Reduced solubility of nonpolar compounds due to added electrolytes
• Formation of buffer salts from acids and bases
• Removal of water by desiccants

Correct Answer: Reduced solubility of nonpolar compounds due to added electrolytes

Q15. Tetracycline forms insoluble complexes with calcium and magnesium. This is primarily a:

• Chemical incompatibility (chelation) causing therapeutic failure
• Physical incompatibility without clinical consequence
• Microbiological incompatibility
• Packaging incompatibility

Correct Answer: Chemical incompatibility (chelation) causing therapeutic failure

Q16. Which resource is widely used to check IV drug compatibility in practice?

• Anatomy atlases
• Trissel’s injectable compatibility data
• USP monographs for identification
• ICH Q1A stability guideline

Correct Answer: Trissel’s injectable compatibility data

Q17. To minimize calcium-phosphate precipitation in TPN, the best practice is:

• Add calcium first, then phosphate, and heat the mixture
• Add phosphate first, keep temperature low, add calcium last with maximum dilution
• Use calcium chloride instead of calcium gluconate
• Increase pH above 7.5

Correct Answer: Add phosphate first, keep temperature low, add calcium last with maximum dilution

Q18. Temperature affects calcium phosphate solubility in TPN such that:

• Higher temperature reduces precipitation risk
• Lower temperature increases precipitation risk
• Higher temperature can increase precipitation risk
• Temperature has no effect

Correct Answer: Higher temperature can increase precipitation risk

Q19. Buffers help prevent precipitation primarily by:

• Increasing ionic strength to force crystallization
• Maintaining pH near maximum solubility of ionizable drugs
• Acting as antimicrobial preservatives
• Increasing viscosity to prevent sedimentation

Correct Answer: Maintaining pH near maximum solubility of ionizable drugs

Q20. Which combination is most likely to precipitate due to common ion effect?

• Silver nitrate with sodium chloride
• Sodium chloride with dextrose
• Lidocaine HCl with sodium chloride
• Potassium chloride with sodium chloride

Correct Answer: Silver nitrate with sodium chloride

Q21. Benzalkonium chloride is incompatible with:

• Nonionic surfactants
• Anionic surfactants forming inactive complexes
• Hydroxypropyl methylcellulose
• EDTA

Correct Answer: Anionic surfactants forming inactive complexes

Q22. Ascorbic acid acting as a reducing agent in formulations exemplifies:

• Physical incompatibility
• Chemical redox incompatibility
• Therapeutic synergism
• pH adjustment

Correct Answer: Chemical redox incompatibility

Q23. A polymorphic transition from a metastable to stable crystal form usually:

• Increases dissolution rate and bioavailability
• Decreases dissolution rate and solubility
• Has no effect on performance
• Always causes chemical degradation

Correct Answer: Decreases dissolution rate and solubility

Q24. To dispense eutectic-forming powders like camphor and menthol, a suitable method is to:

• Levigate with glycerin
• Triturate separately with inert adsorbents like light magnesium carbonate
• Add water to increase hardness
• Heat gently to fuse and solidify

Correct Answer: Triturate separately with inert adsorbents like light magnesium carbonate

Q25. Loss of preservatives such as parabens from solutions in plastic containers is often due to:

• Hydrolysis at neutral pH
• Volatilization at room temperature
• Partitioning/absorption into plastic materials
• Instant photolysis

Correct Answer: Partitioning/absorption into plastic materials

Q26. The Arrhenius equation is employed in incompatibility assessment primarily to:

• Predict photostability under light
• Relate degradation rate to temperature for shelf-life estimation
• Determine buffer capacity
• Calculate isotonicity

Correct Answer: Relate degradation rate to temperature for shelf-life estimation

Q27. EDTA is added to formulations mainly to:

• Increase viscosity
• Chelate metal ions that catalyze oxidation
• Act as a primary antioxidant donating electrons
• Improve taste

Correct Answer: Chelate metal ions that catalyze oxidation

Q28. To prevent caking in suspensions and ease redispersion, formulators typically use:

• Deflocculation agents
• Flocculating agents to form loose aggregates
• High ethanol content
• Strong acids to lower pH

Correct Answer: Flocculating agents to form loose aggregates

Q29. Why can diazepam injection precipitate upon dilution with normal saline?

• pH rises above 10
• Loss of co-solvent reduces drug solubility
• Formation of an insoluble salt
• Oxidation by chloride ions

Correct Answer: Loss of co-solvent reduces drug solubility

Q30. Mixing camphor and phenol causing liquid formation is best classified as:

• Therapeutic antagonism
• Chemical hydrolysis
• Physical incompatibility due to eutectic mixture
• Photodegradation

Correct Answer: Physical incompatibility due to eutectic mixture

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