Large-scale manufacturing of solid dosage forms MCQs With Answer

Introduction:

This quiz set on Large-scale Manufacturing of Solid Dosage Forms is designed specifically for M.Pharm students preparing for advanced coursework and exams in Product Development and Technology Transfer. It focuses on critical aspects of scaling laboratory formulations to commercial production — including equipment selection, scale-up principles, process parameters, material attributes, process analytical technology (PAT), and quality considerations such as in-process testing and validation. Questions probe practical decision-making: choosing between wet granulation and direct compression, controlling segregation, compression science, and transfer documentation. These MCQs aim to deepen understanding of real-world manufacturing challenges and regulatory expectations encountered in the industrial production of tablets and capsules.

Q1. What is the most appropriate scale-up criterion to maintain geometric similarity and predict mixing behavior when scaling a high-shear granulator from lab to production?

• Keeping constant impeller tip speed
• Keeping constant Froude number
• Keeping constant power per unit mass
• Keeping constant residence time

Correct Answer: Keeping constant Froude number

Q2. During scale-up of wet granulation, which parameter best correlates with granule growth and densification produced by kneading action?

• Binder solution viscosity
• Total specific mechanical energy (SME)
• Granulator fill level
• Spray droplet size

Correct Answer: Total specific mechanical energy (SME)

Q3. For direct compression of tablets at large scale, which powder property is most critical to ensure uniform die fill and weight control?

• True density
• Bulk porosity
• Flowability (flow function or Hausner ratio)
• Compressibility index

Correct Answer: Flowability (flow function or Hausner ratio)

Q4. Which PAT tool is most suitable for real-time monitoring of blend uniformity in a rotating bin blender during scale-up?

• Near-Infrared (NIR) spectroscopy
• Torque measurement
• Laser diffraction
• Thermogravimetric analysis (TGA)

Correct Answer: Near-Infrared (NIR) spectroscopy

Q5. In tablet compression scale-up, what is the primary effect of increasing turret speed without adjusting fill depth or feeder settings?

• Improved dissolution rate
• Higher tablet hardness due to increased dwell time
• Reduced die fill leading to weight variation
• Increased blend segregation in the hopper

Correct Answer: Reduced die fill leading to weight variation

Q6. Which of the following is a critical material attribute (CMA) that must be controlled when scaling a formulation containing a deliquescent active pharmaceutical ingredient (API)?

• Particle shape
• Moisture sorption isotherm
• Color index
• Bulk electrical conductivity

Correct Answer: Moisture sorption isotherm

Q7. During transfer from pilot to production for film coating, which parameter adjustment is most commonly needed to maintain equivalent coating weight gain?

• Increase coating solution concentration while keeping spray rate constant
• Decrease inlet air temperature to slow solvent evaporation
• Adjust atomization air pressure and spray gun nozzle size
• Change pan diameter to maintain same bed depth

Correct Answer: Adjust atomization air pressure and spray gun nozzle size

Q8. Which cleaning validation concept is most important in large-scale tableting to prevent cross-contamination between products?

• Visual inspection only
• Use of a single rinse sample from production floor
• Establishing acceptable residue limits (e.g., 10 ppm) based on OEL and worst-case product
• Relying on detergent efficacy without residual testing

Correct Answer: Establishing acceptable residue limits (e.g., 10 ppm) based on OEL and worst-case product

Q9. Which scale-up principle is most relevant when predicting fluidization behavior in a fluid bed dryer during granule drying?

• Maintaining constant power to the motor
• Matching particle Reynolds number and minimum fluidization velocity
• Keeping the same batch weight regardless of bed height
• Using identical spray nozzle type only

Correct Answer: Matching particle Reynolds number and minimum fluidization velocity

Q10. What is the primary challenge related to segregation when increasing batch size for free-flowing granules?

• Excessive moisture uptake during transfer
• Increased probability of size fractionation during transfer, leading to content uniformity issues
• Higher API melting due to scale
• Reduced adhesive properties of binder

Correct Answer: Increased probability of size fractionation during transfer, leading to content uniformity issues

Q11. Which of the following is the best indicator of inadequate lubricant distribution in a large-scale tablet blend?

• Uniform tablet weight
• High ejection forces and localized sticking at punch faces
• Faster dissolution rates
• Reduced friability uniformly across batch

Correct Answer: High ejection forces and localized sticking at punch faces

Q12. For technology transfer documentation, which element provides the most actionable detail for a receiving site to reproduce a production batch?

• High-level product description
• Complete process flow diagram with critical process parameters, set points, and acceptable ranges
• Only the formulation percentage table
• List of vendor names for excipients

Correct Answer: Complete process flow diagram with critical process parameters, set points, and acceptable ranges

Q13. When scaling up compression, which relationship explains why tablet hardness may decrease at higher press speeds if no other changes are made?

• Hardness is controlled solely by punch geometry
• Dwell time decreases with speed, reducing compaction energy if compression system is velocity-sensitive
• Lubricant concentration increases automatically at speed
• Inlet air temperature changes with speed

Correct Answer: Dwell time decreases with speed, reducing compaction energy if compression system is velocity-sensitive

Q14. Which in-process control during granulation best helps determine end-point of wet massing to achieve target granule size and porosity?

• Visual observation only
• Torque or power consumption profile of granulator and granule size distribution sampling
• Final tablet disintegration time
• pH of granulation fluid

Correct Answer: Torque or power consumption profile of granulator and granule size distribution sampling

Q15. What is the principal rationale for performing residence time distribution (RTD) studies in continuous tablet manufacturing during scale-up?

• To estimate dissolution profile of tablets
• To understand material flow, mixing, and to predict blend uniformity and traceability for segregation and hold-up
• To adjust coating parameters
• To measure compression tooling wear

Correct Answer: To understand material flow, mixing, and to predict blend uniformity and traceability for segregation and hold-up

Q16. Which approach best mitigates risk of API degradation caused by heat during large-scale drying of granules?

• Increase inlet air temperature and shorten drying time
• Decrease inlet air temperature and increase airflow or use lower temperature longer drying with monitored endpoint (water activity)
• Rely on visual dryness check
• Omit drying and package wet granules

Correct Answer: Decrease inlet air temperature and increase airflow or use lower temperature longer drying with monitored endpoint (water activity)

Q17. During scale-up, which tablet coating parameter most directly affects surface roughness and film uniformity at production scale?

• Tablet core color only
• Spray droplet size and spray pattern uniformity
• Room lighting during coating
• API particle size

Correct Answer: Spray droplet size and spray pattern uniformity

Q18. In a transfer protocol, what is the purpose of establishing critical quality attributes (CQAs) and linking them to critical process parameters (CPPs)?

• To provide marketing language for labeling
• To ensure that process controls are focused on parameters that directly impact product safety and efficacy and allow risk-based control strategy
• To reduce documentation
• To define personnel roles only

Correct Answer: To ensure that process controls are focused on parameters that directly impact product safety and efficacy and allow risk-based control strategy

Q19. Which statistical approach is most appropriate for demonstrating equivalence of content uniformity between pilot and commercial batches during technology transfer?

• Descriptive statistics only (mean and range)
• Equivalence testing with pre-defined acceptance limits and confidence intervals
• Simple pass/fail single batch comparison
• ANOVA without equivalence margins

Correct Answer: Equivalence testing with pre-defined acceptance limits and confidence intervals

Q20. For scale-up of high-speed tablet presses, which maintenance or tooling consideration becomes more critical to prevent quality drift?

• Frequency of filter changes in HVAC only
• Tooling wear monitoring, alignment checks, and punch-die clearance control
• Color of operator uniforms
• Use of smaller granules regardless of blend

Correct Answer: Tooling wear monitoring, alignment checks, and punch-die clearance control

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