Preformulation studies lay the foundation for drug development by characterizing physicochemical properties that influence stability and formulation design. Key preformulation assessments—solubility, pKa, partition coefficient (log P), polymorphism, hygroscopicity, thermal behavior (DSC/TGA), and drug–excipient compatibility—predict chemical and physical degradation pathways such as hydrolysis, oxidation, photodegradation, and polymorphic transitions. Understanding moisture sensitivity, pH-rate profiles, salt selection, and solid-state stability enables rational excipient choice, packaging, and stability-indicating method development (HPLC, LC-MS). B. Pharm students must grasp these concepts to design robust formulations and interpret stability data during product development. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary goal of preformulation studies in relation to stability?
- To determine commercial pricing of the drug
- To characterize physicochemical properties that predict chemical and physical stability
- To conduct clinical trials
- To market the finished product
Correct Answer: To characterize physicochemical properties that predict chemical and physical stability
Q2. Which property most directly affects a drug’s aqueous solubility and ionization state?
- Polymorphism
- pKa
- Glass transition temperature (Tg)
- Particle morphology
Correct Answer: pKa
Q3. How does hygroscopicity influence drug stability?
- It reduces drug potency by changing particle color only
- It causes moisture uptake leading to hydrolysis, reduced flow, and possible physical transformations
- It increases melting point and stabilizes the drug
- It prevents oxidation by excluding oxygen
Correct Answer: It causes moisture uptake leading to hydrolysis, reduced flow, and possible physical transformations
Q4. Which technique is most appropriate for detecting polymorphic forms in a solid API?
- HPLC
- UV–Vis spectroscopy
- Powder X-ray diffraction (PXRD)
- pH titration
Correct Answer: Powder X-ray diffraction (PXRD)
Q5. What does DSC (Differential Scanning Calorimetry) primarily detect in preformulation?
- Chemical impurities at trace level
- Thermal events such as melting point, crystallization, and glass transition
- Dissolution rate in simulated gastric fluid
- Particle size distribution
Correct Answer: Thermal events such as melting point, crystallization, and glass transition
Q6. Which degradation pathway is most influenced by pH and water activity?
- Photodegradation
- Hydrolysis
- Thermal oxidation
- Mechanical attrition
Correct Answer: Hydrolysis
Q7. Which preformulation parameter helps predict membrane permeation and is relevant to stability in biological systems?
- Log P (partition coefficient)
- Melting point
- Hygroscopicity index
- Thermal conductivity
Correct Answer: Log P (partition coefficient)
Q8. Forced degradation studies are used to:
- Determine commercial formulation appearance
- Generate degradation products to develop stability-indicating analytical methods
- Assess tablet hardness only
- Replace long-term stability studies
Correct Answer: Generate degradation products to develop stability-indicating analytical methods
Q9. Which excipient attribute is most likely to catalyze oxidation of an API?
- High glass transition temperature
- Presence of trace metal ions
- Neutral pH
- Low hygroscopicity
Correct Answer: Presence of trace metal ions
Q10. The Arrhenius equation in stability studies is used to:
- Measure solubility at different pH values
- Predict temperature dependence of reaction rate and estimate shelf life
- Determine particle size distribution
- Identify photodegradation pathways
Correct Answer: Predict temperature dependence of reaction rate and estimate shelf life
Q11. Which choice best describes an amorphous solid compared to its crystalline counterpart?
- Lower free energy and less soluble
- Higher free energy, generally more soluble, but less physically stable
- Always chemically unstable but physically stable
- Identical thermal behavior to crystalline forms
Correct Answer: Higher free energy, generally more soluble, but less physically stable
Q12. Which test would directly assess moisture uptake behavior of a powder?
- Water sorption isotherm (dynamic vapor sorption)
- HPLC purity assay
- IR spectroscopy for functional groups
- pH meter measurement
Correct Answer: Water sorption isotherm (dynamic vapor sorption)
Q13. Why is salt selection important in preformulation?
- Salts always decrease solubility and improve stability
- Salt forms can modify solubility, dissolution rate, hygroscopicity, and chemical stability
- Salt forms eliminate the need for preservatives
- Salt selection is only relevant for injectables
Correct Answer: Salt forms can modify solubility, dissolution rate, hygroscopicity, and chemical stability
Q14. Which analytical method is preferred to develop a stability-indicating assay for degradation products?
- Thermogravimetric analysis (TGA)
- Stability-indicating HPLC or LC–MS
- Powder X-ray diffraction
- Colorimetric pH paper
Correct Answer: Stability-indicating HPLC or LC–MS
Q15. Photostability testing is important because light can cause:
- Only physical discoloration with no chemical change
- Chemical degradation such as photo-oxidation and formation of new degradants
- Immediate sterilization of the product
- Increased melting point
Correct Answer: Chemical degradation such as photo-oxidation and formation of new degradants
Q16. Which factor does NOT typically affect solid-state stability?
- Polymorphic form
- Particle size and surface area
- Ambient humidity
- Color of the manufacturing room walls
Correct Answer: Color of the manufacturing room walls
Q17. The Maillard reaction in formulations involves reaction between:
- Peroxides and antioxidants
- Reducing sugars and primary or secondary amines (API or excipient)
- Metal ions and lipids
- Water and alcohols
Correct Answer: Reducing sugars and primary or secondary amines (API or excipient)
Q18. Isothermal stress testing in preformulation is used to:
- Rapidly screen compatibility by storing mixtures at elevated temperature and humidity
- Determine in vivo bioavailability
- Measure melting point only
- Replace photo-stability testing
Correct Answer: Rapidly screen compatibility by storing mixtures at elevated temperature and humidity
Q19. Which buffering condition should be considered when evaluating pH-dependent degradation?
- Only neutral pH because APIs are neutral
- Range covering pH where degradation rate changes, typically acidic to basic extremes
- Only pH 7 because it’s physiological
- Only extreme pH beyond solubility limits
Correct Answer: Range covering pH where degradation rate changes, typically acidic to basic extremes
Q20. Which excipient class is commonly used to prevent oxidation in formulations?
- Antioxidants (e.g., BHT, ascorbic acid)
- Reducing sugars
- Cellulosic fillers
- Anionic surfactants
Correct Answer: Antioxidants (e.g., BHT, ascorbic acid)
Q21. What role does particle size play in chemical stability?
- Smaller particle size always decreases degradation rates
- Smaller particles increase surface area which can increase degradation rate and dissolution
- Particle size only affects color
- Particle size has no impact on physical or chemical stability
Correct Answer: Smaller particles increase surface area which can increase degradation rate and dissolution
Q22. Which packaging attribute is most important to protect moisture-sensitive APIs?
- Oxygen permeability
- Moisture vapor transmission rate (MVTR) or water vapor barrier properties
- Electrical conductivity
- Transparency to visible light
Correct Answer: Moisture vapor transmission rate (MVTR) or water vapor barrier properties
Q23. When selecting a solvent for stress hydrolysis studies, the solvent should:
- Be completely nonpolar
- Be appropriate to solubilize the API and not introduce new degradation pathways
- Always be water only
- Contain strong oxidants by default
Correct Answer: Be appropriate to solubilize the API and not introduce new degradation pathways
Q24. Which kinetic order describes a constant fraction of drug degrading per unit time?
- Zero-order kinetics
- First-order kinetics
- Second-order kinetics with catalyst only
- Indeterminate kinetics
Correct Answer: First-order kinetics
Q25. Co-crystal formation as a preformulation strategy can improve:
- Only the taste of the API
- Solubility, dissolution rate, and sometimes stability without changing covalent structure
- Color and odor exclusively
- Regulatory classification of the API
Correct Answer: Solubility, dissolution rate, and sometimes stability without changing covalent structure
Q26. Why screen drug–excipient compatibility early in preformulation?
- To eliminate need for stability studies later
- To identify interactions that may accelerate degradation or cause physical changes
- Compatibility screening is optional and rarely useful
- To ensure the excipient changes the API chemical structure
Correct Answer: To identify interactions that may accelerate degradation or cause physical changes
Q27. Which ICH condition is commonly used for long-term stability studies in temperate climates?
- 40°C/75% RH
- 25°C/60% RH
- 5°C refrigerated only
- 60°C dry heat
Correct Answer: 25°C/60% RH
Q28. Peroxide impurities in some excipients (e.g., polyethylene glycols) can cause:
- Reduced solubility
- Oxidative degradation of susceptible APIs
- Improved color stability
- Decreased melting point
Correct Answer: Oxidative degradation of susceptible APIs
Q29. Which analytical approach is best for identifying unknown degradation products formed during stability studies?
- Thermogravimetric analysis (TGA)
- LC–MS/MS (liquid chromatography–mass spectrometry)
- Polarimetry
- Visual inspection
Correct Answer: LC–MS/MS (liquid chromatography–mass spectrometry)
Q30. The Q10 rule in stability estimation suggests that a 10°C rise in temperature will approximately:
- Double or triple the reaction rate depending on activation energy
- Have no effect on reaction rate
- Reduce reaction rate by half
- Change pH of the solution
Correct Answer: Double or triple the reaction rate depending on activation energy
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.
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