Controlled release systems require careful selection of drug candidates based on physicochemical and biological parameters to ensure predictable, safe, and effective therapy. Key selection criteria include solubility, permeability, molecular weight, pKa, therapeutic index, potency, chemical and enzymatic stability, protein binding, and compatibility with polymeric carriers. Considerations such as desired release kinetics, target site, absorption window, polymer biodegradability, and sterilization stability guide formulation strategy. Understanding models of release (diffusion, erosion, osmotic) and in vitro–in vivo correlation is essential for designing robust sustained-release products. This concise MCQ set emphasizes these core concepts and practical selection rules tailored for B. Pharm students. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which pharmacokinetic property of a drug most commonly makes it a good candidate for controlled release formulation?
- Long biological half-life
- Short biological half-life
- Extremely high plasma protein binding
- Very rapid onset of action
Correct Answer: Short biological half-life
Q2. What is the ideal aqueous solubility for drugs intended for diffusion-controlled sustained-release matrix systems?
- Very high solubility (instant dissolution)
- Very low solubility (practically insoluble)
- Moderate aqueous solubility
- Solubility is irrelevant for diffusion systems
Correct Answer: Moderate aqueous solubility
Q3. How does molecular weight typically influence suitability for controlled release via polymeric diffusion matrices?
- Very high molecular weight is preferred
- Low to moderate molecular weight is preferred
- Molecular weight has no impact
- Only polymers’ molecular weight matters, not the drug
Correct Answer: Low to moderate molecular weight is preferred
Q4. Which partition coefficient (log P) range generally favors membrane permeation without excessive tissue retention for controlled-release drugs?
- Highly hydrophilic (log P ≤ -1)
- Moderately lipophilic (log P ~1–3)
- Highly lipophilic (log P >5)
- Any log P value is acceptable
Correct Answer: Moderately lipophilic (log P ~1–3)
Q5. Why is the drug’s pKa important when selecting candidates for oral controlled release intended for systemic absorption?
- It determines color and odor of the formulation
- It dictates the degree of ionization at GI pH and thus permeability
- It only affects stability, not absorption
- pKa is only important for topical drugs
Correct Answer: It dictates the degree of ionization at GI pH and thus permeability
Q6. Which stability characteristic is essential for a drug incorporated into a long-acting implantable device?
- Chemical and enzymatic stability in the polymer and biological milieu
- Only thermal stability during storage
- Stability is not necessary because implants are single-use
- Stability only during sterilization
Correct Answer: Chemical and enzymatic stability in the polymer and biological milieu
Q7. For controlled release formulations, why is high potency (low dose requirement) preferred?
- High potency reduces formulation complexity
- Controlled release devices have limited drug-loading capacity, so low dose per unit is needed
- High potency drugs are always water-soluble
- Potency does not affect device size
Correct Answer: Controlled release devices have limited drug-loading capacity, so low dose per unit is needed
Q8. Which type of therapeutic index is generally most challenging but often desirable to control with sustained-release formulations?
- Extremely wide therapeutic index
- Narrow therapeutic index
- Therapeutic index is irrelevant for controlled release
- Very low safety margin always disqualifies the drug
Correct Answer: Narrow therapeutic index
Q9. Which release mechanism is most commonly exploited in matrix-based controlled release systems?
- Active transport-mediated release
- Diffusion-controlled release
- Enzymatic cleavage only
- Photochemical release
Correct Answer: Diffusion-controlled release
Q10. The Higuchi model describes drug release proportional to which function of time for matrix systems?
- Logarithm of time
- Square root of time
- Exponentially with time
- Linear with time (zero-order)
Correct Answer: Square root of time
Q11. What is the defining feature of zero-order release kinetics?
- Release rate decreases exponentially
- Constant drug release rate independent of concentration
- Release rate proportional to the square root of time
- Immediate complete release followed by no release
Correct Answer: Constant drug release rate independent of concentration
Q12. What is “burst release” in controlled-release formulations?
- Complete prevention of initial release
- Initial rapid release of a large fraction of drug shortly after administration
- Slow release over months without initial phase
- Release only triggered by external stimuli
Correct Answer: Initial rapid release of a large fraction of drug shortly after administration
Q13. How does polymer biodegradability affect controlled release from implantable systems?
- Biodegradable polymers permit release by polymer erosion and do not require removal
- Biodegradability always causes toxic degradation products
- Non-biodegradable polymers are preferred for implants to avoid release
- Biodegradability has no effect on release mechanism
Correct Answer: Biodegradable polymers permit release by polymer erosion and do not require removal
Q14. Why is high encapsulation efficiency desirable in particulate controlled-release formulations?
- It ensures maximal drug wastage
- It minimizes required carrier amount and ensures intended dose delivery
- Encapsulation efficiency only affects color
- Low encapsulation efficiency improves stability
Correct Answer: It minimizes required carrier amount and ensures intended dose delivery
Q15. Which sterilization method is most likely to degrade many small-molecule drugs intended for controlled-release products?
- Gamma irradiation
- Moist heat autoclaving
- Ethylene oxide gas sterilization
- Sterile filtration (0.22 μm)
Correct Answer: Moist heat autoclaving
Q16. How does high plasma protein binding affect controlled-release systemic therapy?
- It increases free drug available for effect
- It reduces free drug concentration and complicates steady-state control
- Protein binding has no pharmacokinetic consequences
- High protein binding always enhances release rate
Correct Answer: It reduces free drug concentration and complicates steady-state control
Q17. What is a major advantage of osmotic pump-based controlled-release systems?
- They provide highly variable release rates
- They can achieve near zero-order release independent of external pH or agitation
- They degrade rapidly in vivo
- They are limited to delivering only proteins
Correct Answer: They can achieve near zero-order release independent of external pH or agitation
Q18. Why is drug–excipient compatibility critical when selecting drug candidates for controlled-release formulations?
- Incompatibility can cause physical or chemical instability, altering release profiles and safety
- Compatibility only affects the color of the final product
- Excipient choice is irrelevant if the drug is potent
- Compatibility only matters during marketing
Correct Answer: Incompatibility can cause physical or chemical instability, altering release profiles and safety
Q19. For chronic therapy requiring uniform plasma levels, which release profile is most desirable?
- Immediate release with frequent dosing
- Zero-order sustained release providing a near-constant rate
- Burst release followed by no release
- First-order release with rapidly declining rate
Correct Answer: Zero-order sustained release providing a near-constant rate
Q20. Which Biopharmaceutics Classification System (BCS) class is generally easiest to design into oral controlled-release forms due to good solubility and permeability?
- BCS Class I (high solubility, high permeability)
- BCS Class II (low solubility, high permeability)
- BCS Class III (high solubility, low permeability)
- BCS Class IV (low solubility, low permeability)
Correct Answer: BCS Class I (high solubility, high permeability)
Q21. How does particle size of drug-loaded microparticles affect release rate in diffusion-controlled systems?
- Larger particles increase surface area and speed release
- Smaller particles increase surface area and generally speed release
- Particle size has no effect on release
- Only polymer size matters, not particle size
Correct Answer: Smaller particles increase surface area and generally speed release
Q22. What is the principal benefit of mucoadhesive controlled-release systems for oral or buccal delivery?
- They decrease residence time in the GI tract
- They increase local or regional residence time and absorption
- They prevent any drug absorption
- Mucoadhesion enhances systemic toxicity only
Correct Answer: They increase local or regional residence time and absorption
Q23. For a transdermal controlled-release patch, which drug properties are most favorable?
- High molecular weight and extreme hydrophilicity
- Low molecular weight and moderate lipophilicity
- Significant ionization at skin pH
- High melting point solids with low permeability
Correct Answer: Low molecular weight and moderate lipophilicity
Q24. Which polymer type is frequently used to form hydrophilic matrices that swell and control drug diffusion?
- Hydrophobic silicone elastomers
- Hydrophilic cellulose derivatives such as HPMC
- Metal salts
- Pure crystalline sugars
Correct Answer: Hydrophilic cellulose derivatives such as HPMC
Q25. In the Korsmeyer–Peppas model for cylindrical matrices, an exponent n ≤ 0.45 indicates which release mechanism?
- Case II transport (polymer relaxation controlled)
- Fickian diffusion-controlled release
- Super case II transport
- Zero-order release independent of diffusion
Correct Answer: Fickian diffusion-controlled release
Q26. Which type of drug is generally a poor candidate for controlled-release therapy?
- Drugs requiring rapid onset and short-term dosing (e.g., acute analgesics)
- Drugs for chronic conditions needing steady plasma levels
- Low-dose potent drugs suitable for implants
- Drugs with long half-lives needing less frequent dosing
Correct Answer: Drugs requiring rapid onset and short-term dosing (e.g., acute analgesics)
Q27. How does a narrow gastrointestinal absorption window influence candidate selection for oral controlled-release formulations?
- It is advantageous because the drug is absorbed everywhere
- It can be a disadvantage because prolonged release may bypass the absorption window
- Absorption window has no impact on oral controlled release
- Narrow windows always improve bioavailability in controlled release
Correct Answer: It can be a disadvantage because prolonged release may bypass the absorption window
Q28. What is an advantage of biodegradable implantable controlled-release devices?
- They require surgical removal after therapy
- They degrade in vivo, eliminating the need for device retrieval
- They always cause chronic inflammation
- Biodegradation prevents any drug release
Correct Answer: They degrade in vivo, eliminating the need for device retrieval
Q29. Why might a controlled-release system incorporate a programmed lag time before drug release?
- To ensure immediate systemic exposure
- To align drug release with circadian rhythms or desired dosing time (chronotherapy)
- Lag time always reduces therapeutic effect
- Lag time makes manufacturing simpler
Correct Answer: To align drug release with circadian rhythms or desired dosing time (chronotherapy)
Q30. Which regulatory documentation is particularly important for demonstrating predictable performance of a controlled-release product?
- Only manufacturing batch records are needed
- In vitro–in vivo correlation (IVIVC) showing relationship between dissolution and plasma levels
- Marketing authorizations without in vitro data
- No additional documentation beyond immediate-release products is required
Correct Answer: In vitro–in vivo correlation (IVIVC) showing relationship between dissolution and plasma levels
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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