Glassy states MCQs With Answer

Grasping glassy states is essential for B. Pharm students who study amorphous drugs, solid-state stability, and formulation design. This concise guide on “Glassy states MCQs With Answer” covers core concepts like glass transition temperature (Tg), molecular mobility, crystallization risk, relaxation phenomena, and characterization techniques such as DSC and XRD. Understanding how processing methods (spray drying, lyophilization, hot-melt extrusion) and excipient interactions influence physical stability and dissolution is vital for developing stable, bioavailable formulations. These SEO-focused MCQs emphasize practical implications for drug performance, storage, and analytical testing, helping students prepare for exams and laboratory work. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What defines a glassy state in pharmaceutical solids?

• A crystalline arrangement with long-range order
• A metastable amorphous solid lacking long-range molecular order
• A liquid at room temperature
• A polymeric gel with crosslinked network

Correct Answer: A metastable amorphous solid lacking long-range molecular order

Q2. The glass transition temperature (Tg) is best described as:

• The temperature at which a crystal melts
• The temperature where an amorphous solid becomes rubbery and molecular mobility increases
• The boiling point of a solvent in a formulation
• The temperature where decomposition begins

Correct Answer: The temperature where an amorphous solid becomes rubbery and molecular mobility increases

Q3. Which analytical technique is most commonly used to determine Tg?

• UV-Visible spectrophotometry
• Differential scanning calorimetry (DSC)
• High-performance liquid chromatography (HPLC)
• Optical microscopy

Correct Answer: Differential scanning calorimetry (DSC)

Q4. A major risk for amorphous pharmaceutical solids during storage is:

• Increased pH
• Recrystallization leading to reduced solubility
• Color fading
• Polymer crosslinking

Correct Answer: Recrystallization leading to reduced solubility

Q5. Which factor lowers Tg of an amorphous drug formulation?

• Dehydration of the sample
• Addition of a plasticizing solvent like water
• Cooling under controlled conditions
• Annealing above Tg

Correct Answer: Addition of a plasticizing solvent like water

Q6. Fragility in glass-forming systems refers to:

• Mechanical brittleness at room temperature
• How rapidly viscosity changes near Tg with temperature
• Chemical instability under light
• Susceptibility to microbial growth

Correct Answer: How rapidly viscosity changes near Tg with temperature

Q7. Which method is NOT typically used to produce amorphous drug solids?

• Spray drying
• Hot-melt extrusion
• Crystallization from a saturated solution
• Lyophilization (freeze-drying)

Correct Answer: Crystallization from a saturated solution

Q8. How does polymer excipient addition generally affect physical stability of an amorphous drug?

• Always causes immediate crystallization
• Can increase Tg and reduce molecular mobility, improving stability
• Removes all residual solvents
• Converts the drug to a crystalline salt

Correct Answer: Can increase Tg and reduce molecular mobility, improving stability

Q9. What does X-ray powder diffraction (XRPD) indicate in glassy systems?

• High-intensity sharp peaks indicating crystallinity
• A diffuse halo pattern consistent with amorphous material
• Molecular weight distribution
• Viscosity of the sample

Correct Answer: A diffuse halo pattern consistent with amorphous material

Q10. Enthalpy relaxation in glasses is related to:

• Energy release as an amorphous solid approaches equilibrium below Tg
• Gaining energy from UV light
• Immediate crystallization upon cooling
• Formation of new covalent bonds

Correct Answer: Energy release as an amorphous solid approaches equilibrium below Tg

Q11. Which parameter is important for predicting physical stability of an amorphous drug?

• Fictive temperature and molecular mobility
• Color and odor
• Surface tension only
• pH of the surrounding medium

Correct Answer: Fictive temperature and molecular mobility

Q12. Moisture typically affects amorphous pharmaceuticals by:

• Increasing Tg and reducing mobility
• Acting as a plasticizer, lowering Tg and increasing recrystallization risk
• Causing immediate covalent crosslinking
• Neutralizing the drug chemically

Correct Answer: Acting as a plasticizer, lowering Tg and increasing recrystallization risk

Q13. The term “co-amorphous” refers to:

• A crystalline drug coexisting with polymer
• An amorphous mixture of two small molecules stabilizing each other
• A hydrated crystalline salt form
• A drug physically mixed with nanoparticles only

Correct Answer: An amorphous mixture of two small molecules stabilizing each other

Q14. Which technique directly shows molecular mobility changes near Tg?

• Differential scanning calorimetry (DSC)
• Dynamic mechanical analysis (DMA)
• Thin layer chromatography (TLC)
• pH meter

Correct Answer: Dynamic mechanical analysis (DMA)

Q15. During DSC heating, an endothermic step without a peak typically indicates:

• Melting of a crystalline drug
• Glass transition (Tg)
• Gasification
• Decomposition

Correct Answer: Glass transition (Tg)

Q16. Which statement about recrystallization from a glass is true?

• It is governed solely by chemical degradation
• It requires molecular mobility sufficient for nucleation and growth
• It cannot occur below Tg under any condition
• It always produces the same polymorph

Correct Answer: It requires molecular mobility sufficient for nucleation and growth

Q17. A stable amorphous formulation strategy often includes:

• Using hygroscopic excipients without protection
• Selecting polymers with high Tg and specific drug–polymer interactions
• Maximizing residual solvent content
• Promoting phase separation

Correct Answer: Selecting polymers with high Tg and specific drug–polymer interactions

Q18. The Kauzmann paradox relates to glassy systems by discussing:

• Excess entropy trend of supercooled liquids compared to crystals
• Solubility limits in water
• Viscosity at room temperature only
• Polymer degradation pathways

Correct Answer: Excess entropy trend of supercooled liquids compared to crystals

Q19. Which processing parameter during spray drying most directly influences glass formation?

• Inlet temperature and drying rate
• Tablet compression force
• pH of spray solution only
• Final coating thickness

Correct Answer: Inlet temperature and drying rate

Q20. What is a practical advantage of amorphous drugs over crystalline forms?

• Lower apparent solubility
• Higher dissolution rate and apparent solubility leading to improved bioavailability
• Greater chemical stability
• Lower manufacturing cost always

Correct Answer: Higher dissolution rate and apparent solubility leading to improved bioavailability

Q21. Phase separation in amorphous solid dispersions can lead to:

• Homogeneous stability
• Localized crystallization and reduced performance
• Increased Tg across the sample
• Immediate sterilization

Correct Answer: Localized crystallization and reduced performance

Q22. In hot-melt extrusion (HME), amorphous conversion relies on:

• Low processing temperature only
• Shear, temperature above Tg of the drug–polymer blend, and mixing
• Complete absence of polymer
• Using water as the only carrier

Correct Answer: Shear, temperature above Tg of the drug–polymer blend, and mixing

Q23. The term “fictive temperature” describes:

• The temperature at which a glass would be in equilibrium with its structure when cooled
• Melting point of a crystalline form
• The boiling point of the solvent used during drying
• The sterilization temperature for pharmaceuticals

Correct Answer: The temperature at which a glass would be in equilibrium with its structure when cooled

Q24. Which of the following indicates physical instability of an amorphous powder during storage?

• Consistent XRPD halo and unchanged DSC
• Appearance of sharp XRD peaks and endothermic melting peak
• No change in dissolution profile
• Constant Tg measured over time

Correct Answer: Appearance of sharp XRD peaks and endothermic melting peak

Q25. Which analytical method can detect molecular interactions (hydrogen bonding) between drug and polymer?

• Fourier-transform infrared spectroscopy (FTIR)
• Scanning electron microscopy (SEM)
• UV-Visible spectroscopy for solids
• Titration

Correct Answer: Fourier-transform infrared spectroscopy (FTIR)

Q26. Which describes an advantage of co-amorphous systems?

• They always lower drug Tg
• Mutual molecular interactions between two small molecules can enhance stability
• They eliminate the need for stability testing
• They are always crystalline

Correct Answer: Mutual molecular interactions between two small molecules can enhance stability

Q27. A high glass-forming ability (GFA) of a drug means:

• It crystallizes immediately upon cooling
• It readily forms and maintains an amorphous state upon cooling from melt
• It is insoluble in common solvents
• It is chemically unstable

Correct Answer: It readily forms and maintains an amorphous state upon cooling from melt

Q28. Which accelerated condition increases risk of recrystallization for amorphous drugs?

• Low temperature and low humidity
• High temperature and high relative humidity
• Storage under nitrogen at -20°C
• Dry vacuum storage

Correct Answer: High temperature and high relative humidity

Q29. Which characterization technique provides morphological information about particles?

• Scanning electron microscopy (SEM)
• DSC for Tg only
• XRPD halo analysis only
• Thermogravimetric analysis (TGA) for molecular weight

Correct Answer: Scanning electron microscopy (SEM)

Q30. Plasticizers in amorphous formulations serve to:

• Increase Tg dramatically
• Lower Tg and increase chain mobility
• Cause crystallization directly
• Eliminate moisture uptake

Correct Answer: Lower Tg and increase chain mobility

Q31. Which kinetic process is critical for the initial stages of crystallization from an amorphous phase?

• Evaporation
• Nucleation
• Protein adsorption
• Crosslinking

Correct Answer: Nucleation

Q32. Solid-state NMR is useful in glassy state studies because it can:

• Detect only crystalline peaks
• Provide molecular-level information on local structure and dynamics
• Measure particle size distribution easily
• Replace DSC for Tg measurement always

Correct Answer: Provide molecular-level information on local structure and dynamics

Q33. Which of the following improves dissolution of a poorly soluble drug via amorphous formulation?

• Converting to a stable crystalline form
• Preparing an amorphous solid or solid dispersion to increase apparent solubility
• Increasing tablet hardness only
• Reducing surface area

Correct Answer: Preparing an amorphous solid or solid dispersion to increase apparent solubility

Q34. Annealing below Tg can lead to:

• Increased non-equilibrium enthalpy and faster crystallization
• Physical aging and enthalpy relaxation toward a lower energy state
• Instant recrystallization to crystal lattice
• Melting of the sample

Correct Answer: Physical aging and enthalpy relaxation toward a lower energy state

Q35. A plasticizer effect of water is most dangerous when storage temperature is:

• Far below Tg
• Near or above Tg after water uptake
• Very low (-80°C)
• Completely irrelevant to Tg

Correct Answer: Near or above Tg after water uptake

Q36. Which term describes the energy barrier for molecular rearrangement leading to crystallization?

• Activation energy for nucleation and growth
• Surface tension only
• Boiling point
• pKa value

Correct Answer: Activation energy for nucleation and growth

Q37. Why is monitoring residual solvent important in amorphous formulations?

• Residual solvent always increases Tg
• Residual solvent can act as plasticizer, lowering Tg and promoting recrystallization
• It only affects taste, not stability
• It cannot be removed during processing

Correct Answer: Residual solvent can act as plasticizer, lowering Tg and promoting recrystallization

Q38. Which formulation approach can inhibit crystallization by reducing molecular mobility?

• Using a low Tg polymer as excipient
• Using high Tg polymers and creating strong drug–polymer interactions
• Maximizing moisture uptake intentionally
• Minimizing polymer content to zero

Correct Answer: Using high Tg polymers and creating strong drug–polymer interactions

Q39. Which experimental observation suggests phase separation in an amorphous dispersion?

• Single Tg corresponding to a homogeneous mixture
• Multiple Tg values or domains observed
• Uniform SEM image without domains
• Consistent dissolution enhancement

Correct Answer: Multiple Tg values or domains observed

Q40. The term “vitrification” in pharmaceutical processing refers to:

• Conversion of a liquid or melt into an amorphous glassy solid
• Formation of a crystalline salt
• Lyophilization failure
• Photodegradation under UV

Correct Answer: Conversion of a liquid or melt into an amorphous glassy solid

Q41. Which of these increases likelihood of crystallization during storage?

• Storage well below Tg with low humidity
• High molecular mobility due to Tg near storage temperature
• Strong drug–polymer hydrogen bonding
• Presence of polymer that raises Tg

Correct Answer: High molecular mobility due to Tg near storage temperature

Q42. Why are amorphous forms often more chemically reactive than crystalline forms?

• They have lower surface area
• They possess higher free energy and molecular mobility, increasing reactivity
• They always contain reactive impurities
• They are inert compared to crystals

Correct Answer: They possess higher free energy and molecular mobility, increasing reactivity

Q43. What is a common indicator of successful amorphization after spray drying?

• Distinct melting peak in DSC and sharp XRPD peaks
• Absence of crystalline peaks in XRPD and single Tg in DSC
• Complete loss of chemical identity
• Increased particle crystallinity under SEM

Correct Answer: Absence of crystalline peaks in XRPD and single Tg in DSC

Q44. Which excipient property is desirable to stabilize amorphous drugs?

• Low glass transition temperature
• High hygroscopicity without barrier protection
• High Tg and ability to form specific intermolecular interactions
• Complete immiscibility with the drug

Correct Answer: High Tg and ability to form specific intermolecular interactions

Q45. In accelerated stability testing for amorphous systems, which measurement is critical?

• Change in color only
• Monitoring Tg, XRPD for crystallinity, and dissolution profile changes
• Measuring tablet hardness only
• Counting microbial colonies

Correct Answer: Monitoring Tg, XRPD for crystallinity, and dissolution profile changes

Q46. Which statement about enthalpy overshoot observed in DSC is correct?

• It indicates sample is crystalline
• It reflects enthalpy relaxation during heating after physical aging
• It measures chemical purity only
• It shows solvent evaporation exclusively

Correct Answer: It reflects enthalpy relaxation during heating after physical aging

Q47. Co-formulation with a salt of the drug to create an amorphous salt can:

• Never change Tg or stability
• Alter Tg and potentially enhance solubility and stability through ionic interactions
• Guarantee crystallization
• Eliminate need for polymer excipients entirely

Correct Answer: Alter Tg and potentially enhance solubility and stability through ionic interactions

Q48. Which process parameter is important to control during lyophilization to favor amorphous cake formation?

• Primary drying shelf temperature and freezing rate
• Tablet compression speed
• Coating pan speed
• Granulator rotor speed only

Correct Answer: Primary drying shelf temperature and freezing rate

Q49. What does a single, composition-dependent Tg in a drug–polymer solid dispersion indicate?

• Complete phase separation
• Homogeneous single-phase amorphous mixture
• Presence of multiple crystalline polymorphs
• Impurity formation

Correct Answer: Homogeneous single-phase amorphous mixture

Q50. Which is an effective strategy to minimize moisture-induced crystallization?

• Store above Tg with high humidity
• Use moisture-protective packaging and include high Tg excipients
• Increase residual solvent content intentionally
• Avoid any polymer or stabilizer

Correct Answer: Use moisture-protective packaging and include high Tg excipients

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com