Pre-formulation protocol design MCQs With Answer

Introduction: Pre-formulation protocol design MCQs With Answer is crafted for M.Pharm students preparing for advanced product development and technology transfer roles. This set of questions focuses on the systematic evaluation of active pharmaceutical ingredients (APIs) and excipients during pre-formulation — covering physicochemical characterization, analytical method requirements, stability and compatibility testing, solubility and dissolution considerations, particle size and flow properties, and strategies for salt or polymorph selection. The MCQs emphasize practical decision-making, interpretation of analytical data, and regulatory expectations for robust pre-formulation protocols. Use these questions to sharpen conceptual understanding, identify knowledge gaps, and reinforce skills needed for formulation design and successful technology transfer.

Q1. Which primary objective of pre-formulation most directly guides selection of suitable solid dosage form and excipients?

• Assessing manufacturing cost of the final product
• Determining physicochemical properties of the API
• Evaluating market demand for dosage forms
• Developing marketing strategy for the drug

Correct Answer: Determining physicochemical properties of the API

Q2. Which technique is most appropriate to detect crystalline polymorphs of an API in pre-formulation?

• High performance liquid chromatography (HPLC)
• Differential scanning calorimetry (DSC)
• X-ray powder diffraction (XRPD)
• Ultraviolet-visible spectroscopy (UV-Vis)

Correct Answer: X-ray powder diffraction (XRPD)

Q3. During pre-formulation, which parameter provides the best initial estimate of lipophilicity affecting membrane permeability?

• Melting point
• Log P (octanol-water partition coefficient)
• Hygroscopicity index
• Bulk density

Correct Answer: Log P (octanol-water partition coefficient)

Q4. Which experiment is essential to determine pKa of an ionizable drug in pre-formulation?

• Thermogravimetric analysis
• Potentiometric titration
• Laser diffraction particle sizing
• Karl Fischer titration

Correct Answer: Potentiometric titration

Q5. Forced degradation studies in a pre-formulation protocol are primarily used to:

• Optimize tablet compression force
• Identify degradation pathways and develop stability-indicating assays
• Measure dissolution in biorelevant media
• Determine particle size distribution

Correct Answer: Identify degradation pathways and develop stability-indicating assays

Q6. Which analytical technique is most useful for detecting drug-excipient chemical interactions during compatibility studies?

• Scanning electron microscopy (SEM)
• Fourier-transform infrared spectroscopy (FTIR)
• Mercury intrusion porosimetry
• Viscosity measurement

Correct Answer: Fourier-transform infrared spectroscopy (FTIR)

Q7. An API shows very low aqueous solubility; which pre-formulation strategy is most appropriate to improve oral bioavailability?

• Decrease particle size and increase surface area (micronization/nanonization)
• Increase storage humidity during manufacturing
• Exclude excipients and use pure API only
• Raise melting point by heating

Correct Answer: Decrease particle size and increase surface area (micronization/nanonization)

Q8. Which property measured in pre-formulation best predicts powder flow during tableting?

• pKa
• Bulk and tapped density with Hausner ratio or Carr’s index
• UV absorption maximum (λmax)
• Log D at pH 7.4

Correct Answer: Bulk and tapped density with Hausner ratio or Carr’s index

Q9. Hygroscopicity testing for an API is critical because excessive moisture uptake can:

• Improve API potency
• Change solid-state form, cause aggregation, and reduce stability
• Lower the partition coefficient to zero
• Enhance color intensity in tablets

Correct Answer: Change solid-state form, cause aggregation, and reduce stability

Q10. Which thermal technique provides both melting point and heat flow information useful for polymorph screening?

• Infrared microscopy
• Differential scanning calorimetry (DSC)
• Atomic absorption spectroscopy
• Zeta potential measurement

Correct Answer: Differential scanning calorimetry (DSC)

Q11. In selecting a salt form of an acidic API to improve solubility, which factor is least relevant?

• Counterion toxicity and regulatory acceptability
• Salt solubility and dissolution rate
• Physical stability and hygroscopicity of the salt
• Color preference of marketing department

Correct Answer: Color preference of marketing department

Q12. For method development of a stability-indicating HPLC assay during pre-formulation, which step is essential?

• Validating method without generating degradation products
• Performing forced degradation to demonstrate separation of drug and degradants
• Measuring only intact API concentration without assessing impurities
• Using arbitrary column chemistry without optimization

Correct Answer: Performing forced degradation to demonstrate separation of drug and degradants

Q13. Which parameter aids in selecting an appropriate dissolution medium for a weakly basic drug?

• API’s melting enthalpy
• API’s pKa and solubility vs pH profile
• API’s particle color
• Packaging material tensile strength

Correct Answer: API’s pKa and solubility vs pH profile

Q14. A high glass transition temperature (Tg) of an amorphous API indicates:

• Greater propensity to crystallize at room temperature
• Lower molecular mobility and better physical stability under ambient conditions
• Immediate chemical degradation in dry conditions
• Incompatibility with all excipients

Correct Answer: Lower molecular mobility and better physical stability under ambient conditions

Q15. Which measurement provides quantitative assessment of moisture content in an API sample?

• Karl Fischer titration
• XRPD peak intensity
• UV-Vis absorbance at λmax
• Plate count for microbiological contamination

Correct Answer: Karl Fischer titration

Q16. In pre-formulation, why is particle size distribution important beyond dissolution rate?

• Only affects product color but not processing
• Impacts content uniformity, flow, compressibility and aerosol performance
• Determines the pKa of the drug
• Dictates the HPLC method parameters directly

Correct Answer: Impacts content uniformity, flow, compressibility and aerosol performance

Q17. Which excipient compatibility finding in early studies would most likely require reformulation?

• Minor physical coating of API surface by an inert lubricant
• Significant chemical degradation of API in presence of an excipient at accelerated conditions
• Improved compressibility on blending with a binder
• Neutral pH shift in placebo dissolution

Correct Answer: Significant chemical degradation of API in presence of an excipient at accelerated conditions

Q18. During solubility profiling, intrinsic dissolution rate (IDR) is used primarily to:

• Assess bulk powder flowability
• Measure dissolution rate independent of particle size
• Determine microbial limits for the API
• Evaluate color stability under light

Correct Answer: Measure dissolution rate independent of particle size

Q19. Why is establishing a pre-formulation protocol important for technology transfer?

• To document marketing claims
• To provide systematic data, methods, and acceptance criteria ensuring consistent scale-up and reproducibility
• To determine final product shelf-layout
• To eliminate the need for analytical method validation

Correct Answer: To provide systematic data, methods, and acceptance criteria ensuring consistent scale-up and reproducibility

Q20. Which outcome from thermal and spectroscopic pre-formulation studies would most strongly suggest a potential incompatibility between API and an excipient?

• Minor shift in tablet hardness
• Appearance of new endothermic/exothermic event in DSC and new peaks in FTIR
• Slight change in bulk density only
• No change in color under ambient light

Correct Answer: Appearance of new endothermic/exothermic event in DSC and new peaks in FTIR

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