Introduction: Preformulation factors for parenteral dosage forms are critical fundamentals every B.Pharm student must master. Preformulation evaluates drug properties—solubility, pKa, stability, partitioning, particle size, and hygroscopicity—and their interaction with excipients, container-closure systems, and sterilization processes. Key considerations include pH, tonicity/osmolality, buffer selection, adsorption, aggregation, degradation pathways (hydrolysis, oxidation, photolysis), preservatives, pyrogen control, and compatibility with infusion media. Understanding these factors guides selection of formulation type (solution, suspension, lyophilized product), packaging materials (Type I glass, elastomers), and stabilization strategies (antioxidants, chelators, cryoprotectants). This knowledge ensures safety, efficacy, and regulatory compliance. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which preformulation parameter most directly influences the choice of buffer for a parenteral solution?
- Melting point of the drug
- Drug pKa
- Particle size distribution
- Viscosity of the vehicle
Correct Answer: Drug pKa
Q2. For an intravenous parenteral solution, why is tonicity adjustment important?
- To enhance drug taste
- To prevent hemolysis and vascular irritation
- To increase solubility of hydrophobic drugs
- To reduce sterilization time
Correct Answer: To prevent hemolysis and vascular irritation
Q3. Which container-closure material is preferred for highly reactive or moisture-sensitive parenterals?
- Type II glass
- Type III glass
- Type I (borosilicate) glass
- Low-density polyethylene (LDPE)
Correct Answer: Type I (borosilicate) glass
Q4. During preformulation, which test identifies potential adsorption of drug molecules to glass or rubber surfaces?
- Viscosity measurement
- Adsorption study by surface contact assay
- Melting point determination
- pKa determination
Correct Answer: Adsorption study by surface contact assay
Q5. Which excipient class is commonly used to protect proteins from aggregation during lyophilization?
- Antioxidants
- Bulking agents and cryoprotectants (e.g., sucrose, trehalose)
- Preservatives (e.g., benzyl alcohol)
- Chelating agents (e.g., EDTA)
Correct Answer: Bulking agents and cryoprotectants (e.g., sucrose, trehalose)
Q6. Which degradation pathway is accelerated by dissolved oxygen in parenteral formulations?
- Hydrolysis
- Oxidation
- Isomerization
- Photodegradation
Correct Answer: Oxidation
Q7. What is the main objective of lyophilization (freeze-drying) in parenteral product development?
- To increase osmolarity
- To convert a drug into a more lipophilic form
- To enhance long-term stability by removing water
- To sterilize the product
Correct Answer: To enhance long-term stability by removing water
Q8. Which parameter is most critical to determine when developing a lyophilized parenteral product to avoid cake collapse?
- Collapse temperature (Tc) and glass transition temperature (Tg’)
- pKa of the drug
- Viscosity of reconstituted solution
- Particle density
Correct Answer: Collapse temperature (Tc) and glass transition temperature (Tg’)
Q9. Why are chelating agents like EDTA included in some parenteral formulations?
- To adjust pH
- To bind metal ions that catalyze oxidative degradation
- To preserve tonicity
- To serve as a primary solvent
Correct Answer: To bind metal ions that catalyze oxidative degradation
Q10. What is a common risk when adding preservatives to multi-dose parenteral formulations?
- Complete sterilization without filtration
- Preservative inactivation by proteins or serum components
- Increased freezing point
- Formation of larger crystals during lyophilization
Correct Answer: Preservative inactivation by proteins or serum components
Q11. Which analytical measurement is essential to ensure particulate matter is within acceptable limits for injectable parenterals?
- pH measurement
- Particulate count by light obscuration or microscopy
- Melting point
- Partition coefficient (log P)
Correct Answer: Particulate count by light obscuration or microscopy
Q12. For a weakly acidic drug, increasing pH typically does what to aqueous solubility?
- Decreases solubility
- Increases solubility by ionization
- Has no effect
- Makes it more lipophilic
Correct Answer: Increases solubility by ionization
Q13. Which sterilization method is preferred for heat-labile parenteral solutions?
- Autoclaving (steam sterilization)
- Dry heat sterilization
- Sterile filtration (0.22 µm) followed by aseptic filling
- Gamma irradiation
Correct Answer: Sterile filtration (0.22 µm) followed by aseptic filling
Q14. What is the role of antioxidants in parenteral formulations?
- To increase viscosity
- To prevent oxidation of susceptible drug molecules
- To act as tonicity modifiers
- To chelate metals
Correct Answer: To prevent oxidation of susceptible drug molecules
Q15. Which property of a protein drug is most likely to be affected by exposure to interfaces (air-liquid, liquid-solid)?
- pKa
- Aggregation and denaturation
- Melting point
- Partition coefficient (log P)
Correct Answer: Aggregation and denaturation
Q16. Why is pH shock during reconstitution a concern for parenteral formulations?
- It can change container closure integrity
- It may cause precipitation or denaturation of the drug
- It increases sterilization efficacy
- It reduces particulate contamination
Correct Answer: It may cause precipitation or denaturation of the drug
Q17. Which test assesses pyrogen contamination in parenteral products?
- Bacterial endotoxin test (LAL) or monocyte activation test
- Particulate counting
- pH titration
- Viscosity profiling
Correct Answer: Bacterial endotoxin test (LAL) or monocyte activation test
Q18. In preformulation, what is the significance of determining drug partition coefficient (log P)?
- It determines melting point
- It helps predict membrane permeability and formulation strategy
- It measures microbial load
- It replaces pKa measurement
Correct Answer: It helps predict membrane permeability and formulation strategy
Q19. Which factor increases the risk of precipitation when a parenteral product is diluted in infusion fluids?
- Matching pH between product and diluent
- High drug concentration near solubility limit and incompatible diluent pH
- Use of isotonic diluent
- Sterile filtration prior to dilution
Correct Answer: High drug concentration near solubility limit and incompatible diluent pH
Q20. What is a common strategy to reduce adsorption of drug to plastic infusion bags or tubing?
- Increase autoclave temperature
- Incorporate surfactants or use non-adsorptive materials
- Lower the drug pKa
- Freeze the solution before infusion
Correct Answer: Incorporate surfactants or use non-adsorptive materials
Q21. Which measurement helps in assessing the stability of suspensions for parenteral use?
- Zeta potential and particle size distribution
- Log P only
- pKa only
- Viscosity at 0°C
Correct Answer: Zeta potential and particle size distribution
Q22. What preformulation concern is specific to monoclonal antibody parenterals compared to small molecules?
- pKa variability
- Immunogenicity risk due to aggregation and formulation-related structural changes
- Melting point determination
- Partition coefficient determination
Correct Answer: Immunogenicity risk due to aggregation and formulation-related structural changes
Q23. Which factor is most likely to promote hydrolytic degradation of a parenteral drug?
- Extremely low moisture for solid formulations
- High water activity and elevated temperature
- Presence of chelators
- Use of antioxidants
Correct Answer: High water activity and elevated temperature
Q24. Why is residual moisture measured in lyophilized parenteral products?
- It indicates the amount of preservative present
- Residual moisture affects chemical stability and cake integrity
- To determine particle size
- To measure osmolarity
Correct Answer: Residual moisture affects chemical stability and cake integrity
Q25. Which factor would you examine to predict the risk of drug adsorption to glass vials?
- Drug lipophilicity and ionic charge
- Drug color only
- Solution viscosity exclusively
- Container label material
Correct Answer: Drug lipophilicity and ionic charge
Q26. What is the primary reason to evaluate compatibility between drug and rubber stoppers used in parenteral packaging?
- To increase drug solubility
- To detect extractables/leachables and potential adsorption or reaction
- To reduce sterility testing requirements
- To change the drug’s pKa
Correct Answer: To detect extractables/leachables and potential adsorption or reaction
Q27. Which physicochemical property governs the need for using solubilizers (cosolvents or surfactants) in parenteral formulations?
- High aqueous solubility
- Poor water solubility (high lipophilicity)
- High melting point
- Low molecular weight only
Correct Answer: Poor water solubility (high lipophilicity)
Q28. When performing preformulation stress testing, which condition is used to evaluate photostability of a parenteral drug?
- Exposure to authorized light sources following ICH Q1B
- Freeze-thaw cycling only
- High humidity at 40°C
- Autoclave sterilization
Correct Answer: Exposure to authorized light sources following ICH Q1B
Q29. Which property determines the rate at which subvisible particles should be monitored in parenteral development?
- Therapeutic index of the drug candidate
- Intended route of administration (intravenous has stricter limits)
- Color of the solution
- Type of glass used for vials only
Correct Answer: Intended route of administration (intravenous has stricter limits)
Q30. In preformulation, why is ionic strength of the formulation important for protein-based parenterals?
- Ionic strength only affects color
- It influences protein solubility, aggregation propensity, and electrostatic interactions
- Ionic strength replaces the need for preservatives
- It is irrelevant for proteins
Correct Answer: It influences protein solubility, aggregation propensity, and electrostatic interactions
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