This set of 30 MCQs covers Formulation of sterile powders for parenteral use, focusing on lyophilization, sterilization techniques, excipients, stability, packaging, reconstitution, and quality control. Designed for B. Pharm students, questions address aseptic processing, terminal sterilization, freeze-drying cycle design, collapse temperature, residual moisture, bulking agents, cryoprotectants, depyrogenation, sterility testing, Bacterial Endotoxin Test, validation parameters, environmental monitoring, vial-closure integrity, and regulatory considerations. Emphasis is on practical formulation challenges, critical process parameters, and troubleshooting to build competence in sterile powder development and QC. Clear options and answers facilitate learning and exam preparation. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which process is primarily used to convert a sterile liquid formulation into a stable sterile powder for parenteral administration?
- Spray drying without aseptic controls
- Lyophilization (freeze-drying) under controlled sterile conditions
- Direct compression
- Hot melt extrusion
Correct Answer: Lyophilization (freeze-drying) under controlled sterile conditions
Q2. In freeze-drying, the temperature above which the product collapses is known as:
- Glass transition temperature of the dried product (Tg)
- Collapse temperature (Tc)
- Melting point (Tm)
- Annealing temperature (Ta)
Correct Answer: Collapse temperature (Tc)
Q3. Which excipient is commonly used as a bulking agent in lyophilized sterile powders to provide cake structure?
- Sodium chloride in high concentration
- Sucrose, mannitol, or trehalose
- Polysorbate 80 at 10% w/v
- Magnesium stearate
Correct Answer: Sucrose, mannitol, or trehalose
Q4. Which method is NOT suitable as a terminal sterilization technique for protein-containing sterile powders?
- Steam autoclaving at high temperature
- Gamma irradiation with controlled dose
- Ethylene oxide sterilization under controlled residual removal
- Filtration of solution before lyophilization (aseptic processing)
Correct Answer: Steam autoclaving at high temperature
Q5. Residual moisture in a lyophilized powder primarily affects which property?
- Color only
- Long-term chemical and physical stability
- Viscosity of the reconstituted solution
- Immediate sterility
Correct Answer: Long-term chemical and physical stability
Q6. Which parameter is most critical when selecting a cryoprotectant for protein stabilization during freeze-drying?
- Ability to form surfactant micelles
- Ability to preferentially hydrate and form a glassy matrix
- High lipid solubility
- Strong covalent binding to the protein
Correct Answer: Ability to preferentially hydrate and form a glassy matrix
Q7. For sterile powders intended for parenteral use, endotoxin control is crucial because endotoxins:
- Enhance protein activity
- Can cause fever and pyrogenic reactions in patients
- Improve powder flow
- Are removed by simple filtration after reconstitution
Correct Answer: Can cause fever and pyrogenic reactions in patients
Q8. Which test is used specifically to detect bacterial endotoxins in sterile powders after reconstitution?
- Sterility test by membrane filtration
- LAL (Limulus Amebocyte Lysate) or alternative endotoxin test
- pH measurement
- Appearance and particulate inspection
Correct Answer: LAL (Limulus Amebocyte Lysate) or alternative endotoxin test
Q9. Aseptic filling before lyophilization is chosen over terminal sterilization when:
- The product is heat-stable and can withstand autoclaving
- The active drug is heat- or radiation-sensitive
- The formulation contains very high concentrations of ethanol
- The product is intended for oral tablets
Correct Answer: The active drug is heat- or radiation-sensitive
Q10. The primary purpose of primary packaging (vial, stopper, and cap) for sterile powders is to:
- Provide attractive branding
- Maintain sterility, moisture control, and physical protection during storage
- Increase the bulk density of the powder
- Neutralize residual solvents
Correct Answer: Maintain sterility, moisture control, and physical protection during storage
Q11. In freeze-drying cycle design, the primary drying phase aims to remove:
- All bound water immediately
- Free (unfrozen) water by desorption
- Frozen solvent (ice) by sublimation under reduced pressure
- Residual organic solvents
Correct Answer: Frozen solvent (ice) by sublimation under reduced pressure
Q12. Collapse of a lyophilized cake during primary drying is most likely if the product temperature exceeds:
- The glass transition temperature of the dry product (Tg)
- The collapse temperature (Tc) of the freeze-concentrated matrix
- The freezing point of pure water
- The annealing temperature only
Correct Answer: The collapse temperature (Tc) of the freeze-concentrated matrix
Q13. Which closure material property is most important for maintaining sterility of lyophilized vials?
- High gas permeability
- Excellent sealing integrity and low moisture transmission
- High antimicrobial coating
- Ability to react with vial glass to form a stronger bond
Correct Answer: Excellent sealing integrity and low moisture transmission
Q14. Which of the following is a common stabilizer used to protect proteins during freezing and drying?
- Polyethylene glycol 8000 as the only excipient
- Sugars such as trehalose or sucrose
- Sodium lauryl sulfate at high concentration
- Hydrochloric acid to lower pH drastically
Correct Answer: Sugars such as trehalose or sucrose
Q15. During aseptic processing, which environmental control is most critical for preventing microbial contamination?
- Ambient humidity only
- Cleanroom classification, HEPA filtration, and controlled air flows
- Surface color and lighting levels
- Temperature of storage refrigerators only
Correct Answer: Cleanroom classification, HEPA filtration, and controlled air flows
Q16. Which parameter is typically monitored to ensure vial-closure integrity after lyophilization?
- pH of the lyophilized cake
- Container closure integrity using dye ingress, vacuum decay, or helium leak testing
- Color of the stopper
- Initial freezing rate
Correct Answer: Container closure integrity using dye ingress, vacuum decay, or helium leak testing
Q17. What is the main regulatory reason to validate aseptic filling processes for sterile powders?
- To reduce manufacturing costs only
- To demonstrate control and reproducibility in preventing contamination and ensuring patient safety
- To increase product viscosity
- To change the drug’s therapeutic indication
Correct Answer: To demonstrate control and reproducibility in preventing contamination and ensuring patient safety
Q18. Which parameter is crucial for reconstitution of lyophilized sterile powders to ensure correct dosing and patient safety?
- Appearance of the powder only
- Choice of solvent, volume for reconstitution, and resulting concentration/osmolarity
- Brand of syringe used only
- Color of the vial cap
Correct Answer: Choice of solvent, volume for reconstitution, and resulting concentration/osmolarity
Q19. Depyrogenation processes are intended to remove or inactivate:
- Viral particles only
- Bacterial endotoxins (pyrogens)
- All microbial spores completely
- Heavy metals in the formulation
Correct Answer: Bacterial endotoxins (pyrogens)
Q20. Which sterilization method relies primarily on ionizing radiation to inactivate microorganisms in finished products?
- Dry heat sterilization
- Gamma irradiation or electron beam sterilization
- Ethylene oxide gas at low temperature
- Membrane filtration
Correct Answer: Gamma irradiation or electron beam sterilization
Q21. The primary goal of annealing during frozen hold prior to primary drying is to:
- Increase the collapse temperature dramatically
- Promote ice crystal growth to improve sublimation rate
- Sterilize the product
- Reduce the pH of the formulation
Correct Answer: Promote ice crystal growth to improve sublimation rate
Q22. Which of the following is an advantage of developing a preservative-free sterile powder for injection?
- Greater risk of microbial growth after reconstitution
- Suitable for single-dose administration and avoids preservative-related toxicity
- Requires less stringent aseptic processing
- Lower regulatory requirements
Correct Answer: Suitable for single-dose administration and avoids preservative-related toxicity
Q23. Which analytical technique is commonly used to measure residual moisture content in lyophilized products?
- Titration with sodium hydroxide
- Karl Fischer titration
- UV-Vis spectroscopy at 280 nm
- Gas chromatography for volatile solvents only
Correct Answer: Karl Fischer titration
Q24. For sterile powder products, validation of sterility testing typically follows:
- No formal guidance is required
- Regulatory compendial methods such as USP <71> or equivalent
- Only in-house rapid tests without documentation
- Visual inspection alone
Correct Answer: Regulatory compendial methods such as USP <71> or equivalent
Q25. Which excipient property helps prevent aggregation of proteins during freeze-drying and storage?
- Surfactant-free formulation only
- Use of sugars that form hydrogen bonding networks and glassy matrices
- High ionic strength to denature proteins
- Use of reactive aldehydes
Correct Answer: Use of sugars that form hydrogen bonding networks and glassy matrices
Q26. During environmental monitoring of an aseptic area, which of these is routinely monitored?
- Surface microbial counts, airborne particle counts, and differential pressure
- Only the color of walls
- Employee satisfaction surveys
- Retail demand forecasts
Correct Answer: Surface microbial counts, airborne particle counts, and differential pressure
Q27. What is the main disadvantage of using mannitol as a bulking agent in lyophilized protein formulations?
- It always reacts covalently with proteins
- It may crystallize during drying causing phase separation and reduced protein stability
- It is too hygroscopic for any use
- It cannot be sterilized
Correct Answer: It may crystallize during drying causing phase separation and reduced protein stability
Q28. Which process parameter is adjusted to control sublimation rate during primary drying?
- pH of the solution only
- Shelf temperature and chamber pressure
- Type of stopper material only
- Brand of lyophilizer software
Correct Answer: Shelf temperature and chamber pressure
Q29. A common cause of particulate formation in reconstituted sterile powders is:
- Use of extremely pure water for injection
- Protein aggregation due to freeze-drying stress or incompatible excipients
- Proper vial-closure integrity
- Correct reconstitution volume used
Correct Answer: Protein aggregation due to freeze-drying stress or incompatible excipients
Q30. Which documentation is essential to demonstrate GMP compliance for sterile powder manufacture?
- Only financial records
- Batch records, validation protocols/reports, SOPs, and environmental monitoring data
- Only marketing brochures
- Employee personal emails
Correct Answer: Batch records, validation protocols/reports, SOPs, and environmental monitoring data
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.
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