Introduction to pre-formulation studies MCQs With Answer

Introduction to pre-formulation studies MCQs With Answer

This quiz set on Introduction to Pre‑formulation Studies is designed for M.Pharm students preparing for advanced coursework and exams in Product Development and Technology Transfer. It covers core concepts such as physicochemical characterization, solid‑state behavior, solubility and dissolution, stability, excipient compatibility, and analytical approaches used to guide formulation decisions. Questions are crafted to test conceptual understanding and applied reasoning—identifying critical pre‑formulation parameters, interpreting instrumental data, and making formulation‑relevant choices such as salt selection, particle size considerations, and moisture control. Use these MCQs to assess readiness, identify knowledge gaps, and strengthen decision‑making skills essential for successful product development.

Q1. What is the primary objective of pre‑formulation studies in drug product development?

• To optimize manufacturing equipment layouts
• To evaluate physicochemical properties of the drug substance to guide formulation and processing
• To determine marketing strategy and pricing
• To perform clinical trials for bioavailability

Correct Answer: To evaluate physicochemical properties of the drug substance to guide formulation and processing

Q2. Which parameter is most critical to assess when choosing between salt and free‑base forms to improve oral bioavailability?

• Melting point
• pKa and aqueous solubility
• Color and odor
• Glass transition temperature

Correct Answer: pKa and aqueous solubility

Q3. Differential scanning calorimetry (DSC) in pre‑formulation is primarily used to detect which property?

• Particle size distribution
• Thermal transitions such as melting point and glass transition
• Hygroscopicity under controlled humidity
• Partition coefficient in octanol‑water

Correct Answer: Thermal transitions such as melting point and glass transition

Q4. Which solid‑state technique provides definitive evidence for crystalline versus amorphous nature of a drug?

• Ultraviolet spectroscopy
• X‑ray powder diffraction (XRPD)
• Viscometry
• HPLC retention time

Correct Answer: X‑ray powder diffraction (XRPD)

Q5. A drug candidate is highly hygroscopic. Which pre‑formulation strategy is most appropriate to mitigate stability risk?

• Increase milling to reduce particle size
• Use moisture‑protective packaging and consider converting to less hygroscopic salt or coating
• Raise the storage temperature
• Add water to the formulation during manufacturing

Correct Answer: Use moisture‑protective packaging and consider converting to less hygroscopic salt or coating

Q6. Why is determination of particle size distribution critical during pre‑formulation?

• It directly determines the chemical stability of the API
• It influences dissolution rate, content uniformity, flowability, and compression behavior
• It replaces the need for solubility testing
• It measures the dose potency of the API

Correct Answer: It influences dissolution rate, content uniformity, flowability, and compression behavior

Q7. Which measurement best estimates the lipophilicity of a drug candidate during pre‑formulation?

• Intrinsic dissolution rate
• Log P or log D (octanol‑water partition coefficient/distribution coefficient)
• Thermogravimetric analysis (TGA)
• Moisture sorption isotherm

Correct Answer: Log P or log D (octanol‑water partition coefficient/distribution coefficient)

Q8. Intrinsic dissolution rate (IDR) experiments are particularly useful because they:

• Replace in vivo bioavailability data
• Provide a discriminating measure of the dissolution behavior of the pure drug substance independent of particle size
• Measure the pKa of the drug
• Directly quantify polymorphic transitions during storage

Correct Answer: Provide a discriminating measure of the dissolution behavior of the pure drug substance independent of particle size

Q9. Which of the following indicates potential drug‑excipient incompatibility during pre‑formulation?

• No change in DSC thermogram when mixed
• Appearance of new peaks or disappearance of drug melting endotherm in DSC and changes in XRPD
• Identical FTIR spectra for physical mixture and individual components
• Constant pH of solution after mixing

Correct Answer: Appearance of new peaks or disappearance of drug melting endotherm in DSC and changes in XRPD

Q10. A compound shows multiple endothermic events in DSC and several distinct diffraction peaks in XRPD. This is most consistent with:

• An amorphous single‑phase material
• A hydrated or polymorphic crystalline material with multiple forms
• A volatile oil
• A pure solvated amorphous dispersion

Correct Answer: A hydrated or polymorphic crystalline material with multiple forms

Q11. Which pre‑formulation test helps to predict tablet compaction behavior and tendency for capping or lamination?

• Karl Fischer titration
• Compression profiling and powder rheology such as Carr’s index and Hausner ratio
• UV absorption spectrum
• Pore size analysis by mercury intrusion only

Correct Answer: Compression profiling and powder rheology such as Carr’s index and Hausner ratio

Q12. In salt selection studies, which attribute is least likely to be improved by converting to a salt form?

• Aqueous solubility
• Chemical stability toward oxidation
• Crystal habit and processability
• Permeability across biological membranes in all cases

Correct Answer: Permeability across biological membranes in all cases

Q13. Moisture sorption isotherms obtained during pre‑formulation primarily inform which decisions?

• Choice of chromatography column for assay
• Packaging requirements, storage conditions, and need for desiccants
• Selection of dissolution medium
• Animal species for toxicity testing

Correct Answer: Packaging requirements, storage conditions, and need for desiccants

Q14. A drug shows pH‑dependent solubility with high solubility at low pH and low solubility at high pH. What is the likely ionization behavior?

• Non‑ionizable neutral compound
• Basic compound (weak base) with protonation at low pH
• Acidic compound (weak acid) with deprotonation at low pH
• Zwitterion that is insoluble at all pH

Correct Answer: Basic compound (weak base) with protonation at low pH

Q15. Which analytical approach is most appropriate to develop a stability‑indicating method during pre‑formulation?

• Generic UV method without forced degradation studies
• Forced degradation studies combined with selective chromatographic separation and validated assay
• Only mass balance measurements by gravimetry
• HPLC with no specificity assessment

Correct Answer: Forced degradation studies combined with selective chromatographic separation and validated assay

Q16. Which property best explains why amorphous forms often show higher apparent solubility than their crystalline counterparts?

• Higher crystallinity index
• Higher thermodynamic free energy and lack of long‑range order
• Higher melting point
• Lower molecular weight

Correct Answer: Higher thermodynamic free energy and lack of long‑range order

Q17. In pre‑formulation, what is the significance of determining the drug’s pKa?

• It identifies melting behavior only
• It helps predict ionization state across physiological pH, solubility, and permeability
• It provides direct information about polymorphic transitions
• It is only useful for topical formulations

Correct Answer: It helps predict ionization state across physiological pH, solubility, and permeability

Q18. Which experimental result during pre‑formulation would most strongly indicate a risk of photodegradation?

• No change in assay after light exposure
• Significant loss of potency and appearance of new photoproduct peaks after controlled light exposure
• Unchanged DSC thermogram
• Stable XRPD pattern

Correct Answer: Significant loss of potency and appearance of new photoproduct peaks after controlled light exposure

Q19. Why is assessment of drug wettability important in pre‑formulation for orally disintegrating tablets or suspensions?

• Wettability governs color stability only
• Poor wettability may reduce dissolution rate and hinder uniform dispersion in suspensions
• Wettability determines the pKa of the drug
• It has no impact on bioavailability

Correct Answer: Poor wettability may reduce dissolution rate and hinder uniform dispersion in suspensions

Q20. During pre‑formulation, conversion of an API to an amorphous solid dispersion (ASD) is considered primarily to:

• Decrease its hygroscopicity always
• Improve apparent solubility and dissolution rate for poorly soluble drugs
• Ensure crystalline stability under all conditions
• Increase melting point

Correct Answer: Improve apparent solubility and dissolution rate for poorly soluble drugs

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