Chemical factors influencing drug degradation are central to pharmaceutical stability and shelf-life. This introduction outlines key concepts such as hydrolysis, oxidation, photodegradation, pH-dependent pathways, temperature effects and catalysis by metal ions or excipients. Understanding reaction kinetics, the Arrhenius relationship, activation energy, solvent and ionic-strength effects, and microenvironmental pH helps predict degradation routes and design stabilizing strategies. Practical topics include chelators, antioxidants, moisture control and solid-state versus solution stability. Mastery of these chemical principles enables rational formulation, proper storage conditions and accurate stability testing. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which chemical reaction is most commonly responsible for degradation of ester-containing drugs in aqueous formulations?
- Oxidation by molecular oxygen
- Hydrolysis catalyzed by acids or bases
- Photolytic cleavage under UV light
- Isomerization to inactive stereoisomers
Correct Answer: Hydrolysis catalyzed by acids or bases
Q2. How does pH typically affect the rate of drug hydrolysis?
- Rate is independent of pH
- Acidic and basic catalysis often accelerate hydrolysis compared with neutral pH
- Hydrolysis only occurs at extremely low pH
- Higher pH always slows hydrolysis
Correct Answer: Acidic and basic catalysis often accelerate hydrolysis compared with neutral pH
Q3. Which statement best describes autoxidation of pharmaceuticals?
- Autoxidation requires visible light but not oxygen
- Autoxidation is a radical chain process involving oxygen and often initiators
- Autoxidation is a reversible acid–base equilibrium
- Autoxidation is catalyzed exclusively by enzymes
Correct Answer: Autoxidation is a radical chain process involving oxygen and often initiators
Q4. Which excipient is most likely to catalyze drug oxidation through trace metal contamination?
- Magnesium stearate with iron traces
- Lactose as a reducing sugar
- Sodium chloride at neutral purity
- Microcrystalline cellulose (pure)
Correct Answer: Magnesium stearate with iron traces
Q5. Which approach is most effective to prevent metal-catalyzed oxidation in formulations?
- Increase formulation pH to 12
- Add chelating agents like EDTA
- Remove water by adding glycerin
- Expose product to air to oxidize metals
Correct Answer: Add chelating agents like EDTA
Q6. What role does temperature play in chemical degradation according to the Arrhenius equation?
- Rate constants decrease exponentially with temperature
- Temperature has no effect on reaction rate
- Reaction rates generally increase exponentially with temperature, dependent on activation energy
- Only enzymatic degradation is temperature-dependent
Correct Answer: Reaction rates generally increase exponentially with temperature, dependent on activation energy
Q7. Which mechanism describes light-induced degradation of a drug molecule?
- Photochemical excitation leading to bond cleavage or radical formation
- pH shift causing hydrolysis
- Heat generation from ambient light causing denaturation
- Ion exchange in the solid state
Correct Answer: Photochemical excitation leading to bond cleavage or radical formation
Q8. Why are aromatic amines particularly susceptible to oxidative degradation?
- They form stable carbocations resistant to oxidation
- The lone pair on nitrogen facilitates formation of reactive radicals or quinone-imine species
- They are insoluble and therefore protected
- Aromatic amines are inert to oxygen
Correct Answer: The lone pair on nitrogen facilitates formation of reactive radicals or quinone-imine species
Q9. Which property of solvents can influence chemical degradation of solubilized drugs?
- Dielectric constant and protic vs. aprotic nature
- Only the color of the solvent
- Solvent viscosity only at 0°C
- Solvent has no effect once dissolved
Correct Answer: Dielectric constant and protic vs. aprotic nature
Q10. In solid-state formulations, which factor often slows chemical degradation compared to solution?
- Higher molecular mobility in the solid state
- Restricted molecular mobility and reduced solvent-mediated reactions
- Increased oxygen diffusion
- Enhanced catalytic activity of excipients
Correct Answer: Restricted molecular mobility and reduced solvent-mediated reactions
Q11. Which degradation pathway involves internal nucleophilic attack leading to ring closure in peptides or small molecules?
- Oxidative cleavage
- Intramolecular cyclization (e.g., diketopiperazine formation in peptides)
- Photodimerization
- Saponification by base hydrolysis
Correct Answer: Intramolecular cyclization (e.g., diketopiperazine formation in peptides)
Q12. Which analytical parameter is crucial to monitor to detect early chemical degradation during stability testing?
- Particle size only
- Degradation product profile and assay of active drug by validated methods
- Tablet hardness exclusively
- Odor changes alone without chemical assay
Correct Answer: Degradation product profile and assay of active drug by validated methods
Q13. How does ionic strength of a solution influence drug degradation reactions?
- Ionic strength only affects biological activity, not chemical reactions
- It can alter reaction rates by stabilizing or destabilizing charged transition states
- Ionic strength always inhibits degradation
- Ionic strength is irrelevant for hydrolysis
Correct Answer: It can alter reaction rates by stabilizing or destabilizing charged transition states
Q14. Which degradation is most likely for β-lactam antibiotics under moist, warm conditions?
- Denaturation into stereoisomers
- β-Lactam ring hydrolysis leading to inactive acids
- Polymerization due to light exposure
- Formation of stable metal complexes
Correct Answer: β-Lactam ring hydrolysis leading to inactive acids
Q15. Why is lactose problematic in some formulations during storage?
- Lactose is inert and causes no reactions
- Lactose can undergo Maillard reaction with primary amines to form colored degradation products
- Lactose chelates metal ions and prevents oxidation
- Lactose removes water and stabilizes drugs
Correct Answer: Lactose can undergo Maillard reaction with primary amines to form colored degradation products
Q16. Which antioxidant is commonly used to inhibit oxidation in formulations?
- EDTA as a reducing agent
- Butylated hydroxytoluene (BHT) or ascorbic acid as radical scavengers
- Sodium chloride to remove oxygen
- Magnesium oxide to promote oxidation
Correct Answer: Butylated hydroxytoluene (BHT) or ascorbic acid as radical scavengers
Q17. Which functional group is least susceptible to hydrolysis under physiological pH?
- Esters
- Amides (especially secondary amides)
- Acid chlorides
- Anhydrides
Correct Answer: Amides (especially secondary amides)
Q18. How do buffers influence chemical stability of pH-sensitive drugs?
- Buffers maintain ionic strength but not pH
- Buffers maintain a fixed pH that can stabilize or accelerate pH-dependent degradation depending on buffer pH and catalytic species
- Buffers always accelerate degradation
- Buffers are only important for biological assays, not chemical stability
Correct Answer: Buffers maintain a fixed pH that can stabilize or accelerate pH-dependent degradation depending on buffer pH and catalytic species
Q19. Which of the following increases the rate of nucleophilic substitution reactions in drug degradation?
- Decreasing electrophilicity of the reaction center
- Presence of strong nucleophiles and polar aprotic solvent
- Lower temperature and steric hindrance
- Removal of nucleophiles from the medium
Correct Answer: Presence of strong nucleophiles and polar aprotic solvent
Q20. Which measure reduces photodegradation risk in a liquid pharmaceutical product?
- Use of clear glass and exposure to daylight
- Packaging in amber glass or opaque containers and adding UV absorbers
- Adding metal salts to absorb light energy
- Increasing pH above 9 to block light effects
Correct Answer: Packaging in amber glass or opaque containers and adding UV absorbers
Q21. Which degradation pathway commonly affects primary amine-containing drugs stored with reducing sugars?
- Transesterification
- Maillard glycation producing brown pigments and potential degradation products
- Photodimerization
- Radical-mediated halogenation
Correct Answer: Maillard glycation producing brown pigments and potential degradation products
Q22. What is the effect of dissolved oxygen removal (degassing) on oxidative stability?
- Degassing increases oxidation by concentrating radicals
- Removing dissolved oxygen reduces the rate of oxygen-mediated oxidation
- Degassing has no effect on oxidation
- Degassing converts oxidation to hydrolysis
Correct Answer: Removing dissolved oxygen reduces the rate of oxygen-mediated oxidation
Q23. Which chemical factor explains accelerated degradation in hygroscopic solid dosage forms?
- Hygroscopicity reduces mobility and prevents reactions
- Adsorbed water creates a microaqueous phase that promotes hydrolysis and ionic reactions
- Hygroscopicity protects drugs from light
- Hygroscopic materials always prevent oxidation
Correct Answer: Adsorbed water creates a microaqueous phase that promotes hydrolysis and ionic reactions
Q24. Racemization of chiral drugs is promoted by which chemical factor?
- Strong nucleophiles only
- Acid or base catalysis that facilitates proton abstraction at stereocenters adjacent to carbonyls
- Photostability at all wavelengths
- Presence of hydrophobic excipients exclusively
Correct Answer: Acid or base catalysis that facilitates proton abstraction at stereocenters adjacent to carbonyls
Q25. Which method can be used to predict shelf-life using chemical kinetics?
- Only organoleptic observation
- Applying the Arrhenius equation to accelerated stability data to estimate degradation rates at storage temperature
- Measuring tablet hardness over time
- Using pH strips alone
Correct Answer: Applying the Arrhenius equation to accelerated stability data to estimate degradation rates at storage temperature
Q26. Which structural feature most increases susceptibility to photodegradation?
- Presence of conjugated double bonds or aromatic chromophores
- High aliphatic saturation with no chromophores
- Absence of heteroatoms
- Extremely high molecular weight only
Correct Answer: Presence of conjugated double bonds or aromatic chromophores
Q27. Which phenomenon describes chemical degradation accelerated by trace basic impurities in excipients?
- Enzymatic catalysis
- Base-catalyzed hydrolysis or deprotonation-enhanced reactions
- Photocatalysis only
- Neutralization of active drug
Correct Answer: Base-catalyzed hydrolysis or deprotonation-enhanced reactions
Q28. Which degradation reaction is typical for tertiary alcohols under typical storage conditions?
- Easily undergo hydrolysis to carboxylic acids
- Generally resistant to simple hydrolysis but may dehydrate under strong acid or heat
- Rapidly oxidized to aldehydes
- Readily form Schiff bases
Correct Answer: Generally resistant to simple hydrolysis but may dehydrate under strong acid or heat
Q29. How do plasticizers in polymeric packaging sometimes influence drug stability?
- Plasticizers are inert and never affect drugs
- They can migrate (extractables) and catalyze degradation or react with drug molecules
- They always improve stability by scavenging moisture
- They increase the drug’s melting point preventing degradation
Correct Answer: They can migrate (extractables) and catalyze degradation or react with drug molecules
Q30. Which is a common chemical strategy to stabilize pH-sensitive drugs in solution?
- Use unbuffered water only
- Formulate with an appropriate buffer at a pH that minimizes the specific degradation rate, and include stabilizers if needed
- Adjust pH to extremes without testing
- Rely on light exposure to neutralize reactive species
Correct Answer: Formulate with an appropriate buffer at a pH that minimizes the specific degradation rate, and include stabilizers if needed
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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