Crystalline and amorphous forms MCQs With Answer

Crystalline and amorphous forms profoundly influence drug solid-state behavior, stability, and bioavailability — essential concepts for B. Pharm students. Crystalline solids display long-range order, defined lattice energy, sharp melting points, and characteristic X-ray diffraction peaks, while amorphous forms possess disordered molecular arrangements, a glass transition, higher free energy, enhanced apparent solubility, and greater physical instability. Mastery of polymorphism, characterization techniques (PXRD, DSC, FTIR, Raman, microscopy), preparation methods (spray drying, freeze-drying, milling), and recrystallization kinetics is vital for formulation development and stability assessment. These MCQs probe physicochemical principles, analytical interpretation, and formulation implications to build practical competence. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary distinguishing feature of a crystalline solid compared to an amorphous solid?

• Presence of a glass transition temperature instead of a melting point
• Long-range periodic atomic or molecular order
• Higher free energy and molecular mobility
• Random packing with no distinct X-ray pattern

Correct Answer: Long-range periodic atomic or molecular order

Q2. Which analytical technique is most directly used to identify long-range order in crystalline materials?

• Differential scanning calorimetry (DSC)
• Powder X-ray diffraction (PXRD)
• Fourier-transform infrared spectroscopy (FTIR)
• Scanning electron microscopy (SEM)

Correct Answer: Powder X-ray diffraction (PXRD)

Q3. Which thermal event is characteristic of an amorphous pharmaceutical solid on DSC?

• An endothermic sharp melting peak
• An exothermic crystallization followed by Tg
• A glass transition (Tg) usually as a step change in baseline
• A distinct polymorphic transition endotherm

Correct Answer: A glass transition (Tg) usually as a step change in baseline

Q4. How does solubility of an amorphous form generally compare to its crystalline counterpart?

• Amorphous form typically has lower solubility
• They always have identical solubility
• Amorphous form typically has higher apparent solubility
• Crystalline form is always more soluble due to lattice energy

Correct Answer: Amorphous form typically has higher apparent solubility

Q5. Which statement best explains why amorphous forms have higher apparent solubility?

• Greater lattice energy in amorphous solids
• Higher molecular disorder gives higher free energy and chemical potential
• They form stronger hydrogen bonds with solvent
• Lower surface area reduces dissolution rate

Correct Answer: Higher molecular disorder gives higher free energy and chemical potential

Q6. Which preparation method is commonly used to produce amorphous solid dispersions of poorly soluble drugs?

• Recrystallization from a saturated solvent
• Spray drying with a polymeric carrier
• Slow cooling of a saturated melt
• Hydrothermal synthesis

Correct Answer: Spray drying with a polymeric carrier

Q7. In PXRD, what pattern indicates an amorphous material?

• Sharp, well-defined Bragg peaks
• A single sharp peak at low angle
• A broad diffuse halo with no sharp peaks
• Multiple high-intensity peaks corresponding to polymorphs

Correct Answer: A broad diffuse halo with no sharp peaks

Q8. Which factor most promotes recrystallization of an amorphous drug during storage?

• Storage below glass transition temperature (Tg)
• Presence of moisture acting as a plasticizer
• Inclusion of a high Tg polymeric stabilizer
• Low molecular mobility and strong intermolecular interactions

Correct Answer: Presence of moisture acting as a plasticizer

Q9. What is the significance of the glass transition temperature (Tg) for amorphous drug stability?

• Tg indicates the temperature of melting for amorphous solids
• Below Tg molecular mobility is reduced, improving physical stability
• Tg predicts chemical degradation rates directly
• Tg is irrelevant for formulation considerations

Correct Answer: Below Tg molecular mobility is reduced, improving physical stability

Q10. Which DSC observation indicates recrystallization of an amorphous sample upon heating?

• A baseline step without any peak
• An exothermic peak followed by an endothermic melting peak
• A single sharp endothermic melting peak only
• No thermal events over the measured range

Correct Answer: An exothermic peak followed by an endothermic melting peak

Q11. Polymorphism refers to:

• The amorphous-to-crystalline conversion only
• The ability of a compound to exist in multiple crystalline forms
• The variation of particle size within a batch
• The formation of co-crystals exclusively

Correct Answer: The ability of a compound to exist in multiple crystalline forms

Q12. Which property is usually higher for crystalline forms compared to amorphous forms?

• Free energy
• Solubility
• Lattice energy and thermodynamic stability
• Molecular mobility

Correct Answer: Lattice energy and thermodynamic stability

Q13. What does a decrease in enthalpy of fusion compared between two crystalline forms suggest?

• The form with lower enthalpy is more stable thermodynamically
• The form with lower enthalpy will always have higher solubility
• Enthalpy of fusion is unrelated to stability
• The higher enthalpy form is always metastable

Correct Answer: The form with lower enthalpy is more stable thermodynamically

Q14. Which spectroscopic change might suggest loss of crystalline order?

• Sharpening of vibrational bands in FTIR
• Disappearance or broadening of characteristic Raman bands
• Appearance of new crystalline lattice vibration peaks
• No change in baseline or peaks

Correct Answer: Disappearance or broadening of characteristic Raman bands

Q15. Ostwald’s rule of stages describes:

• Direct formation of the most stable polymorph first
• The sequence in which metastable forms may appear before the stable form
• How amorphous solids always crystallize to a single form
• The kinetics of dissolution only

Correct Answer: The sequence in which metastable forms may appear before the stable form

Q16. Which technique can probe molecular mobility and relaxation in amorphous drugs?

• Polarized light microscopy for birefringence
• Dielectric spectroscopy
• Particle size analysis by laser diffraction
• UV-visible spectroscopy

Correct Answer: Dielectric spectroscopy

Q17. Which of the following best describes enthalpy relaxation in an aged amorphous sample?

• Immediate melting at lower temperature
• Exothermic heat release near Tg due to structural relaxation
• Sharp endothermic melting peak indistinguishable from crystalline melting
• No thermal signature upon heating

Correct Answer: Exothermic heat release near Tg due to structural relaxation

Q18. Why are polymers used in amorphous solid dispersions?

• To decrease Tg and promote recrystallization
• To inhibit molecular mobility and stabilize the amorphous state
• To induce rapid crystallization during storage
• To lower drug solubility intentionally

Correct Answer: To inhibit molecular mobility and stabilize the amorphous state

Q19. Which statement about residual solvents in amorphous materials is correct?

• Residual solvents always increase Tg and stabilize the amorphous form
• Residual solvents act as plasticizers and can lower Tg, increasing mobility
• Residual solvents have no impact on physical stability
• Residual solvents convert amorphous into crystalline instantly

Correct Answer: Residual solvents act as plasticizers and can lower Tg, increasing mobility

Q20. A metastable polymorph typically shows which of the following compared to the stable polymorph?

• Lower solubility and higher melting point
• Higher free energy, higher solubility, and possibly lower melting point
• Identical thermodynamic properties but different color
• Greater long-term thermodynamic stability

Correct Answer: Higher free energy, higher solubility, and possibly lower melting point

Q21. Which microscopy observation indicates crystallinity under polarized light?

• No birefringence and uniform dark field
• Strong birefringence and interference colors
• Only amorphous halos visible
• Complete translucency without contrast

Correct Answer: Strong birefringence and interference colors

Q22. Which factor does NOT generally favor formation of an amorphous solid from a melt?

• Very high cooling rate
• Presence of glass-forming excipients
• Slow cooling allowing molecular packing
• Mechanical milling to induce disorder

Correct Answer: Slow cooling allowing molecular packing

Q23. In the context of dissolution behavior, what is a potential advantage of an amorphous drug form?

• Lower initial dissolution rate but longer release
• Higher initial apparent dissolution rate and supersaturation potential
• Predictable crystalline lattice-limited dissolution
• No difference compared to crystalline form

Correct Answer: Higher initial apparent dissolution rate and supersaturation potential

Q24. Which measurement helps quantify degree of crystallinity in a semi-crystalline sample?

• Comparison of integrated PXRD peak intensities to an amorphous baseline
• Visual inspection under ordinary light
• Measuring only melting point temperature
• Particle size distribution analysis

Correct Answer: Comparison of integrated PXRD peak intensities to an amorphous baseline

Q25. Which kinetic process governs the early-stage formation of crystalline nuclei from an amorphous phase?

• Bulk diffusion-limited growth only
• Homogeneous or heterogeneous nucleation followed by crystal growth
• Immediate bulk conversion without nucleation barrier
• Exclusive surface adsorption phenomena

Correct Answer: Homogeneous or heterogeneous nucleation followed by crystal growth

Q26. Which of the following is a common indicator of polymorphic transition during thermal analysis?

• A single, unchanged baseline on DSC
• An endothermic peak at Tm followed by an exotherm
• An endothermic peak at a lower temperature preceding the main melt
• A reversible Tg shift without other events

Correct Answer: An endothermic peak at a lower temperature preceding the main melt

Q27. What role does moisture sorption isotherm data play in assessing amorphous formulations?

• It predicts color changes only
• Helps evaluate hygroscopicity and risk of plasticization-induced recrystallization
• Is irrelevant for solid-state stability
• Only useful for crystalline salts

Correct Answer: Helps evaluate hygroscopicity and risk of plasticization-induced recrystallization

Q28. Which technique can detect nanoscale crystalline domains within an otherwise amorphous matrix?

• Routine optical microscopy without polarizers
• Pair distribution function (PDF) analysis from total X-ray scattering
• Simple melting point determination
• Conventional UV spectroscopy

Correct Answer: Pair distribution function (PDF) analysis from total X-ray scattering

Q29. For solid dispersions, which property of the polymer excipient is most beneficial to maintain the drug in an amorphous state?

• Low molecular weight and high plasticizing ability
• High Tg and strong intermolecular interactions with the drug
• Complete immiscibility with the drug
• Crystallinity similar to the drug

Correct Answer: High Tg and strong intermolecular interactions with the drug

Q30. Which regulatory concern is specific to amorphous drug products compared to crystalline ones?

• Amorphous products never require stability studies
• Potential for physical instability leading to changes in dissolution and bioavailability over shelf life
• Amorphous forms are automatically considered impurities
• Regulators forbid use of amorphous forms in oral dosage forms

Correct Answer: Potential for physical instability leading to changes in dissolution and bioavailability over shelf life

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