Containers and closures for parenterals are essential to maintain sterility, stability, and safety of injectable drugs. This topic explores container types (glass vials, ampoules, prefilled syringes, cartridges), closure materials (butyl, bromobutyl, chlorobutyl elastomers, coated stoppers), and critical concepts such as container-closure integrity (CCI), extractables and leachables, glass Type I/II/III differences, delamination, and silicone oil effects on proteins. B.Pharm students will study regulatory expectations, pharmacopeial tests, sterilization compatibility, transit and storage stresses, and analytical methods for leakage and particulate control. Pay attention to packaging materials, compatibility studies, and quality control tests emphasized by pharmacopeias. Case examples and exam-focused points appear in the MCQs. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which glass type is preferred for parenteral formulations that are chemically sensitive and require highest resistance to hydrolytic attack?
- Type I borosilicate glass
- Type II treated soda-lime glass
- Type III soda-lime glass
- Flint glass
Correct Answer: Type I borosilicate glass
Q2. Which elastomeric stopper material is most commonly used for lyophilized powders due to low permeability and good seal properties?
- Natural rubber
- Bromobutyl rubber
- Silicone rubber
- Chloroprene rubber
Correct Answer: Bromobutyl rubber
Q3. Container-closure integrity (CCI) testing aims primarily to detect what risk for parenterals?
- Chemical incompatibility between drug and container
- Loss of sterility due to leakage
- Formation of visible particulates
- Incorrect label adhesion
Correct Answer: Loss of sterility due to leakage
Q4. Which pharmacopeial method is commonly used for detecting microbial ingress in a closure system?
- Dye ingress test
- Helium leak detection
- Vacuum decay with microbial challenge
- pH shift assay
Correct Answer: Vacuum decay with microbial challenge
Q5. What is the main concern associated with silicone oil used as a lubricant in prefilled syringes?
- Increased sterility
- Protein aggregation and particle formation
- Improved drug solubility
- Reduced glass strength
Correct Answer: Protein aggregation and particle formation
Q6. Delamination of glass vials results in:
- Improved drug stability
- Release of flakes or lamellae into the solution
- Better headspace control
- Enhanced crimp seal
Correct Answer: Release of flakes or lamellae into the solution
Q7. Which closure attribute is most critical for lyophilized product stability during storage?
- Torque of crimp cap
- Headspace oxygen and moisture permeability
- Color of the stopper
- Presence of external dust
Correct Answer: Headspace oxygen and moisture permeability
Q8. Extractables and leachables studies are performed primarily to assess:
- Mechanical strength of container
- Toxicological risk from migrated substances
- Label durability under humidity
- Visual clarity of the container
Correct Answer: Toxicological risk from migrated substances
Q9. Which sterilization method can adversely affect some elastomeric closures by causing oxidation or loss of elasticity?
- Gamma irradiation
- Dry heat at appropriate temperatures
- Filtration
- Ethylene oxide under controlled conditions
Correct Answer: Gamma irradiation
Q10. What is the role of a crimp seal (aluminum cap) on a vial?
- To provide a tamper-evident and mechanical seal over the stopper
- To increase container fragility
- To absorb moisture from headspace
- To act as primary sterile barrier
Correct Answer: To provide a tamper-evident and mechanical seal over the stopper
Q11. Which parameter is measured in helium leak testing for container-closure systems?
- Permeability to oxygen only
- Mass of extractables
- Actual leak rate as helium flow or pressure decay
- Optical density of solution
Correct Answer: Actual leak rate as helium flow or pressure decay
Q12. Why are coated elastomer stoppers used for biologics?
- To increase gas permeability
- To provide a barrier reducing extractables and drug adsorption
- To make stopper color uniform
- To enhance thermal conductivity
Correct Answer: To provide a barrier reducing extractables and drug adsorption
Q13. Which container is least likely to contribute leachables from glass itself?
- Type I borosilicate vial
- Type III soda-lime vial
- Plastic HDPE bottle
- Flint glass ampoule
Correct Answer: Type I borosilicate vial
Q14. The USP <381> elastomeric closures monograph primarily addresses:
- Container closure integrity for glass vials
- Toxicological testing of leachables
- Quality and testing specifications for elastomeric closures
- Labeling requirements for parenterals
Correct Answer: Quality and testing specifications for elastomeric closures
Q15. Which test detects the presence of a sub-visible particulate generation due to container-closure interaction?
- Particulate count by light obscuration
- Dye ingress test
- pH measurement
- Endotoxin limit test
Correct Answer: Particulate count by light obscuration
Q16. For sterile drug products, primary packaging must:
- Be decorative and colorful
- Act as the first line of protection to maintain sterility
- Be made exclusively of glass
- Be permeable to water vapor
Correct Answer: Act as the first line of protection to maintain sterility
Q17. Which phenomenon involves chemical species migrating from container or closure into the drug product under storage?
- Delamination
- Leaching (leachables)
- Adsorption at the interface
- Osmotic shock
Correct Answer: Leaching (leachables)
Q18. Which closure property is most important to prevent ingress of atmospheric moisture into a lyophilized vial?
- Elastic modulus of the rubber
- Barrier properties and seal integrity
- Color of the aluminum seal
- Height of the stopper above vial top
Correct Answer: Barrier properties and seal integrity
Q19. Which test can simulate transport stress to evaluate seal robustness of vial closures?
- Freeze-thaw cycling only
- Vibration and shock testing
- Helium leak testing only
- UV exposure test
Correct Answer: Vibration and shock testing
Q20. Adsorption of drug to stopper surfaces is a concern because it can:
- Increase drug potency
- Reduce delivered dose and affect stability
- Make tubing more flexible
- Enhance optical clarity
Correct Answer: Reduce delivered dose and affect stability
Q21. Which closure design reduces coring when a needle penetrates the stopper?
- Highly cross-linked elastomer with low tack
- Soft, low density rubber
- Uncoated natural rubber
- Loose-fitting cap
Correct Answer: Highly cross-linked elastomer with low tack
Q22. During lyophilization, which attribute of the stopper is critical for controlled collapse onto the vial mouth?
- Thermal conductivity of aluminum cap
- Compressibility and resiliency of the stopper
- Opacity of the glass
- pH of the formulation
Correct Answer: Compressibility and resiliency of the stopper
Q23. Which material is commonly used for prefilled syringe barrels to minimize interactions with biologics?
- Polycarbonate
- Borosilicate glass
- Low-density polyethylene
- Metal alloy
Correct Answer: Borosilicate glass
Q24. What is a primary advantage of using flip-off caps on prefilled syringes or vials?
- They enhance primary sterility by themselves
- Provide tamper evidence and easy access for healthcare workers
- Reduce oxygen permeability dramatically
- Eliminate need for stoppers
Correct Answer: Provide tamper evidence and easy access for healthcare workers
Q25. Which analytical approach is typically used to identify extractables from packaging under exaggerated conditions?
- Mass spectrometry coupled with chromatography
- Visual inspection only
- Simple pH paper
- Sterility testing
Correct Answer: Mass spectrometry coupled with chromatography
Q26. Which container feature is most relevant to reduce breakage risk during autoclave sterilization?
- Thin-walled glass design
- Appropriate glass annealing and wall thickness
- Use of uncoated elastomers
- Absence of crimp caps
Correct Answer: Appropriate glass annealing and wall thickness
Q27. Which closure test will detect gross leakage under vacuum by visual observation of dye penetration?
- Dye ingress test
- Helium mass spectrometry
- Light obscuration particle count
- Extractables profiling
Correct Answer: Dye ingress test
Q28. How does pH of a formulation influence container-closure selection?
- pH only affects label adhesion, not material choice
- Acidic or alkaline pH can increase leaching or glass surface attack, influencing material choice
- Neutral pH always causes delamination
- pH has no impact on elastomer interactions
Correct Answer: Acidic or alkaline pH can increase leaching or glass surface attack, influencing material choice
Q29. What is the principal benefit of using plastic primary containers (e.g., cyclic olefin polymer syringes) over glass for some biologics?
- Higher extractables profile
- Reduced risk of glass delamination and breakage
- Increased oxygen permeability always
- Lower manufacturing cost only
Correct Answer: Reduced risk of glass delamination and breakage
Q30. Which regulatory concern must be addressed when changing a closure supplier for an approved parenteral product?
- Only packaging color change notification is needed
- Demonstration of equivalence for CCI, extractables/leachables, and compatibility studies
- No testing is required if dimensions match
- Only cost analysis must be provided
Correct Answer: Demonstration of equivalence for CCI, extractables/leachables, and compatibility studies
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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