Formulation of protein DDS MCQs With Answer

Formulation of protein DDS MCQs With Answer is designed to help M. Pharm students master core principles behind designing safe, stable, and effective protein drug delivery systems. Proteins are large, sensitive biomolecules prone to denaturation, aggregation, oxidation, and enzymatic degradation. Successful dosage design therefore demands informed choices on routes, excipients, containers, processes, and analytics. This quiz set spans stabilization mechanisms (lyophilization, surfactants, buffers), advanced carriers (PLGA depots, liposomes), microenvironment control, sterilization and device concerns, pulmonary and mucosal delivery, and critical analytical assays. Each question is crafted to test applied understanding of formulation science and translate it into problem-solving for real-world development and regulatory expectations in Drug Delivery Systems (MPH 102T).

Q1. Which excipient most effectively stabilizes proteins during lyophilization by replacing water via hydrogen bonding?

• Trehalose
• Polysorbate 80
• Sodium chloride
• Methionine

Correct Answer: Trehalose

Q2. To minimize interfacial stress–induced aggregation during shaking, filling, or pumping, the most appropriate excipient is:

• Polysorbate 80 (nonionic surfactant)
• Potassium phosphate buffer
• Zinc oxide
• Sodium alginate

Correct Answer: Polysorbate 80 (nonionic surfactant)

Q3. For PLGA-based protein depots, which change most predictably slows drug release?

• Increasing the lactide:glycolide ratio from 50:50 to 75:25
• Using acid-terminated PLGA instead of ester end-capped PLGA
• Reducing polymer molecular weight
• Adding pore formers such as NaCl

Correct Answer: Increasing the lactide:glycolide ratio from 50:50 to 75:25

Q4. Acidic microclimate within degrading PLGA can cause protein acylation and aggregation. A common mitigation is:

• Inclusion of basic salts (e.g., Mg(OH)2) to neutralize acidic microclimate
• Using phosphate buffer at pH 8.5
• Autoclaving the filled depot to sterilize
• Adding lactose as a reducing sugar stabilizer

Correct Answer: Inclusion of basic salts (e.g., Mg(OH)2) to neutralize acidic microclimate

Q5. During primary drying of a lyophilization cycle, product temperature should be controlled primarily to remain below:

• The formulation’s collapse temperature (Tc)
• The buffer pKa
• The glass transition temperature of the dried cake (Tg)
• Room temperature (25°C)

Correct Answer: The formulation’s collapse temperature (Tc)

Q6. The preferred terminal sterilization/bioburden control approach for protein injectables is:

• Sterile filtration through a 0.22 μm low-protein-binding membrane followed by aseptic processing
• Steam sterilization at 121°C for 30 minutes
• Dry heat sterilization at 250°C for 30 minutes
• Gamma irradiation at 25 kGy

Correct Answer: Sterile filtration through a 0.22 μm low-protein-binding membrane followed by aseptic processing

Q7. To mitigate oxidative degradation of methionine and tryptophan residues in protein formulations, a commonly used additive is:

• Methionine as an antioxidant scavenger
• Lactose as a stabilizer
• Sodium chloride as a tonicity agent
• Ferric chloride as a catalyst

Correct Answer: Methionine as an antioxidant scavenger

Q8. To reduce Asn deamidation while maintaining conformational stability, a widely used protein buffer strategy is:

• Histidine buffer around pH 5.5
• Phosphate buffer at pH 8.0
• Borate buffer at pH 9.2
• Carbonate buffer at pH 10

Correct Answer: Histidine buffer around pH 5.5

Q9. For pulmonary delivery of proteins to the alveolar region via dry powder inhaler, the ideal mass median aerodynamic diameter (MMAD) is:

• 1–5 μm
• 0.1–0.5 μm
• 6–15 μm
• 20–50 μm

Correct Answer: 1–5 μm

Q10. To prevent adsorption and interfacial denaturation of proteins on glass and stainless-steel surfaces, a suitable approach is:

• Inclusion of polysorbate 20 to occupy interfaces and surfaces
• Use of high ionic strength (>1 M NaCl)
• Adjustment to isoelectric point (pI)
• Adding copper ions

Correct Answer: Inclusion of polysorbate 20 to occupy interfaces and surfaces

Q11. Which sugar is preferred in lyophilized protein formulations to avoid Maillard browning while providing glassy-state stabilization?

• Sucrose (non-reducing sugar)
• Lactose (reducing sugar)
• Glucose (reducing sugar)
• Maltose (reducing sugar)

Correct Answer: Sucrose (non-reducing sugar)

Q12. PEGylation most directly increases a protein’s systemic half-life by:

• Increasing hydrodynamic radius and reducing renal filtration
• Increasing receptor binding affinity
• Raising formulation pH
• Enhancing photostability by light absorption

Correct Answer: Increasing hydrodynamic radius and reducing renal filtration

Q13. Which analytical technique is most routinely used to quantify monomer loss and soluble high–molecular weight aggregates in protein solutions?

• Size-exclusion chromatography (SEC-HPLC)
• Differential scanning calorimetry (DSC)
• Circular dichroism (CD)
• Fourier transform infrared spectroscopy (FTIR)

Correct Answer: Size-exclusion chromatography (SEC-HPLC)

Q14. A mucoadhesive absorption enhancer that transiently opens tight junctions and is widely studied for nasal peptide delivery is:

• Chitosan
• Polyvinyl alcohol
• Polylactic acid
• Polyethylene glycol 400

Correct Answer: Chitosan

Q15. In in situ forming PLGA depots (e.g., PLGA dissolved in N-methyl-2-pyrrolidone), depot formation after injection occurs primarily via:

• Solvent exchange–driven phase inversion
• Photo-crosslinking by UV light
• Thermal gelation at 37°C of poloxamers
• Ionic gelation with calcium ions

Correct Answer: Solvent exchange–driven phase inversion

Q16. What is the principal purpose of an annealing step during lyophilization?

• To grow ice crystals and crystallize excipients, reducing resistance to vapor flow and shortening primary drying
• To sterilize the product by heat
• To increase residual moisture for better cake elasticity
• To raise the collapse temperature by adding surfactant

Correct Answer: To grow ice crystals and crystallize excipients, reducing resistance to vapor flow and shortening primary drying

Q17. Which excipient commonly serves as a bulking agent, tonicity adjuster, and forms an elegant lyophilized cake due to its crystallinity?

• Mannitol
• Urea
• Glycerol
• Acetone

Correct Answer: Mannitol

Q18. Compared with acid-terminated PLGA, ester end-capped PLGA typically results in:

• Slower polymer degradation and slower protein release
• Faster polymer degradation and faster protein release
• No change in release behavior
• Immediate burst release only

Correct Answer: Slower polymer degradation and slower protein release

Q19. A known leachable from prefilled syringe needles that can induce protein aggregation, especially at low concentrations, is:

• Tungsten
• Calcium sulfate
• Silicon dioxide
• Sodium citrate

Correct Answer: Tungsten

Q20. The most appropriate compendial method to measure residual moisture in lyophilized protein products is:

• Karl Fischer titration
• Loss on drying at 105°C
• Gas chromatography headspace ethanol assay
• UV–Vis absorbance at 280 nm

Correct Answer: Karl Fischer titration

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