Powder diffraction and its pharmaceutical applications MCQs With Answer

Powder diffraction is a core analytical technique in pharmaceutical solid-state characterization, especially X-ray powder diffraction (XRPD). It reveals crystallinity, phase identification, polymorphism, lattice parameters, and crystallite size—critical factors in drug development, quality control, and formulation stability. B. Pharm students must understand instrumentation, Bragg’s law, sample preparation, data interpretation, and quantitative methods like Rietveld refinement and RIR analysis. Applications include detecting polymorphic transformations, measuring amorphous content, monitoring manufacturing processes, and ensuring regulatory compliance for stability and bioavailability. This concise review links fundamental principles with practical pharmaceutical uses to prepare you for analytical challenges. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the basic principle behind powder X-ray diffraction in pharmaceuticals?

• Constructive interference of X-rays scattered by crystal planes (Bragg’s law)
• Emission of characteristic X-rays from excited atoms
• Absorption of neutrons by atomic nuclei
• Elastic scattering of electrons in TEM

Correct Answer: Constructive interference of X-rays scattered by crystal planes (Bragg’s law)

Q2. Which radiation source is most commonly used in laboratory XRPD instruments for pharmaceutical analysis?

• Copper Kα (Cu Kα) radiation
• Cobalt gamma radiation
• Ultraviolet laser
• Neutron beam

Correct Answer: Copper Kα (Cu Kα) radiation

Q3. Which equation expresses Bragg’s law used to relate diffraction angle and interplanar spacing?

• nλ = 2d sinθ
• E = hν
• λ = hc/E
• d = √(h^2 + k^2 + l^2)

Correct Answer: nλ = 2d sinθ

Q4. What structural information can be obtained directly from powder diffraction data?

• Unit cell dimensions (a, b, c, α, β, γ)
• Atomic mass and electron density
• Surface area and porosity
• Optical rotation and refractive index

Correct Answer: Unit cell dimensions (a, b, c, α, β, γ)

Q5. The Scherrer equation in XRPD is primarily used to:

• Estimate average crystallite size (peak broadening analysis)
• Determine atomic coordinates in a structure
• Measure thermal expansion coefficient
• Quantify amorphous content directly

Correct Answer: Estimate average crystallite size (peak broadening analysis)

Q6. What is the main purpose of Rietveld refinement in powder diffraction?

• Refine crystal structure and quantify phase amounts by whole-pattern fitting
• Separate ionic species by chromatography
• Measure viscosity of pharmaceutical suspensions
• Determine solubility product constants

Correct Answer: Refine crystal structure and quantify phase amounts by whole-pattern fitting

Q7. How does XRPD help in identifying polymorphism in an active pharmaceutical ingredient (API)?

• Identify and distinguish polymorphic forms based on unique peak patterns
• Measure pH-dependent solubility directly
• Determine particle zeta potential
• Quantify pesticide residues in API

Correct Answer: Identify and distinguish polymorphic forms based on unique peak patterns

Q8. What effect does preferred orientation (texture) have on a powder diffraction pattern?

• Distortion of peak intensities due to non-random crystallite orientation
• Complete disappearance of all diffraction peaks
• Generation of fluorescence background only
• Uniform peak broadening independent of angle

Correct Answer: Distortion of peak intensities due to non-random crystallite orientation

Q9. How does an amorphous pharmaceutical material typically appear in an XRPD pattern?

• Broad diffuse halo instead of sharp Bragg peaks
• Sharp, high-intensity Bragg peaks
• Multiple split peaks due to twinning
• Complete absence of any x-ray interaction

Correct Answer: Broad diffuse halo instead of sharp Bragg peaks

Q10. The Relative Intensity Ratio (RIR) method in powder diffraction is used for:

• Quantitative phase analysis using an internal standard and RIR values
• Determining melting point by extrapolation
• Evaluating dissolution rate in media
• Measuring tensile strength of tablets

Correct Answer: Quantitative phase analysis using an internal standard and RIR values

Q11. What is a good sample preparation practice for XRPD of pharmaceutical powders?

• Finely ground, randomly oriented powder on a flat sample holder
• Large single crystals glued to a mount
• Liquid samples measured in a cuvette without preparation
• Coarse granules piled to maintain original morphology

Correct Answer: Finely ground, randomly oriented powder on a flat sample holder

Q12. Which instrumental component directly detects diffracted X-rays in XRPD systems?

• X-ray detector (e.g., scintillation counter or position-sensitive detector)
• Mass spectrometer detector
• Thermal conductivity detector
• Optical microscope camera

Correct Answer: X-ray detector (e.g., scintillation counter or position-sensitive detector)

Q13. Peak indexing in powder diffraction is used to:

• Assign Miller indices (hkl) and calculate d-spacings for peaks
• Measure dissolution half-life
• Identify chemical impurities by retention time
• Determine pKa values of drugs

Correct Answer: Assign Miller indices (hkl) and calculate d-spacings for peaks

Q14. Which factors commonly cause peak broadening in XRPD patterns?

• Small crystallite size and lattice microstrain
• Increased solvent viscosity
• Elevated humidity during weighing
• High ionic strength of buffer solutions

Correct Answer: Small crystallite size and lattice microstrain

Q15. What can variable-temperature XRPD reveal about a pharmaceutical solid?

• Phase transitions and thermal stability (e.g., polymorph conversion on heating)
• Color changes under light exposure
• Viscosity changes with temperature
• pH-dependent solubility profiles

Correct Answer: Phase transitions and thermal stability (e.g., polymorph conversion on heating)

Q16. In applying the Scherrer equation, what is the typical value used for the shape factor K?

• Use a shape factor (K) typically ~0.9 in the Scherrer equation
• Use a refractive index close to 1.3 for corrections
• Apply a viscosity correction factor of 0.5
• Multiply d-spacing by Avogadro’s number

Correct Answer: Use a shape factor (K) typically ~0.9 in the Scherrer equation

Q17. How is powder diffraction applied during pharmaceutical formulation development?

• Monitor solid-state changes during formulation like polymorphic conversion and crystallinity changes
• Predict oral absorption based solely on molecular weight
• Replace all stability testing with XRPD alone
• Measure microbial contamination levels in tablets

Correct Answer: Monitor solid-state changes during formulation like polymorphic conversion and crystallinity changes

Q18. What is a key difference between single-crystal diffraction and powder diffraction?

• Single-crystal gives full 3D structure; powder gives averaged diffraction and phase ID
• Powder diffraction yields atomic coordinates directly without modeling
• Single-crystal cannot provide space group information
• Powder diffraction is used only for liquids

Correct Answer: Single-crystal gives full 3D structure; powder gives averaged diffraction and phase ID

Q19. Grazing incidence XRPD is particularly useful for:

• Surface-sensitive measurements for thin films and coatings (grazing incidence)
• Measuring bulk tablet porosity in-situ
• Determining solubility in gastric fluid
• Assessing enzyme activity on surfaces

Correct Answer: Surface-sensitive measurements for thin films and coatings (grazing incidence)

Q20. What advantage does synchrotron radiation provide for powder diffraction studies?

• High brilliance, tunable wavelength for high-resolution and time-resolved studies
• Cheaper and more portable than lab X-ray sources
• Eliminates need for sample preparation entirely
• Produces neutrons for neutron diffraction studies

Correct Answer: High brilliance, tunable wavelength for high-resolution and time-resolved studies

Q21. Why is polymorph control important from a regulatory perspective?

• Polymorph control is critical due to effects on stability, solubility and bioavailability
• XRPD results are never used in regulatory submissions
• Polymorphs can be ignored if the API is potent
• Regulatory bodies only accept NMR data for solid-state characterization

Correct Answer: Polymorph control is critical due to effects on stability, solubility and bioavailability

Q22. How is an internal standard used to quantify amorphous content by XRPD?

• An internal crystalline standard is mixed to quantify amorphous fraction by comparison
• Use only visual color standards to estimate amorphous content
• Rely exclusively on tablet hardness testers
• Quantify amorphous content using pH meters

Correct Answer: An internal crystalline standard is mixed to quantify amorphous fraction by comparison

Q23. A systematic shift in peak positions in an XRPD pattern usually indicates:

• Changes in lattice parameters (e.g., unit cell expansion or contraction)
• Changes in melting point directly
• Increase in solution viscosity
• Degradation of API by microbes

Correct Answer: Changes in lattice parameters (e.g., unit cell expansion or contraction)

Q24. What do Miller indices (hkl) describe in crystallography?

• Orientation of lattice planes used to describe diffraction peaks
• Concentration of active ingredient in mg per tablet
• Number of hydrogen bond donors
• Optical birefringence angles

Correct Answer: Orientation of lattice planes used to describe diffraction peaks

Q25. Why is whole-pattern (e.g., Rietveld) fitting advantageous for quantitative phase analysis?

• Handles overlapping peaks and provides more accurate quantitative phase analysis
• Eliminates need for calibration standards
• Always gives exact atomic positions without refinement
• Measures drug release rates in dissolution testing

Correct Answer: Handles overlapping peaks and provides more accurate quantitative phase analysis

Q26. What is required to start a Rietveld refinement?

• An initial crystal structure model is required to start refinement
• No prior information is ever needed to refine a structure
• It requires only infrared spectra as input
• It is only applicable for amorphous samples

Correct Answer: An initial crystal structure model is required to start refinement

Q27. What is the typical detection limit of XRPD for a minor crystalline phase in a pharmaceutical mixture?

• Typically around 1–5% by weight for well-crystallized phases
• Less than 0.0001% for any phase
• More than 50% for all minor phases
• Exactly 10% for all instruments

Correct Answer: Typically around 1–5% by weight for well-crystallized phases

Q28. What is microabsorption and why is it a concern in quantitative XRPD?

• Microabsorption can bias quantitative results when phases have very different absorption coefficients
• It increases detector sensitivity uniformly across peaks
• It causes only peak position shifts without affecting intensity
• It can be corrected by lowering lab temperature to 0°C

Correct Answer: Microabsorption can bias quantitative results when phases have very different absorption coefficients

Q29. Combining XRPD with DSC (differential scanning calorimetry) allows you to:

• Correlate thermal events with structural changes (e.g., melting, polymorphic transitions)
• Replace dissolution testing in vivo
• Measure only surface pH changes
• Determine color stability under visible light exclusively

Correct Answer: Correlate thermal events with structural changes (e.g., melting, polymorphic transitions)

Q30. What can XRPD reveal when applied to finished tablet formulations?

• Detect and quantify crystalline drug forms and polymorphs in formulated dosage forms
• Measure tablet friability directly without mechanical testing
• Replace HPLC for assay content determination
• Determine microbial load in sterile products

Correct Answer: Detect and quantify crystalline drug forms and polymorphs in formulated dosage forms

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