Introduction: Understanding physicochemical properties influencing controlled drug delivery is essential for B. Pharm students preparing formulations with predictable release profiles. Key concepts include solubility, lipophilicity (log P), pKa and ionization, molecular size and shape, crystallinity versus amorphous state, diffusion coefficient, polymer–drug interactions, swelling, degradation, permeability, and stability. These properties determine drug release kinetics, absorption, bioavailability, and compatibility with excipients and delivery systems such as matrices, nanoparticles, transdermals, and osmotic pumps. Mastery of these parameters enables rational design of controlled-release systems and troubleshooting in formulation development. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which physicochemical property primarily determines a drug’s ability to partition into lipid membranes and thus affects transcellular permeability?
- Particle size
- Log P (lipophilicity)
- pKa
- Crystallinity
Correct Answer: Log P (lipophilicity)
Q2. The pH-partition hypothesis explains drug absorption based on which pair of properties?
- Molecular weight and viscosity
- Solubility and melting point
- pKa and environmental pH
- Surface charge and zeta potential
Correct Answer: pKa and environmental pH
Q3. A drug with high aqueous solubility but very low lipophilicity is most likely to have which absorption limitation?
- Poor dissolution rate
- Poor membrane permeability
- Excessive protein binding
- Rapid chemical degradation
Correct Answer: Poor membrane permeability
Q4. Which parameter directly influences the diffusion coefficient of a drug in a polymer matrix according to Stokes–Einstein relation?
- Drug ionization state
- Drug molecular radius
- Polymer glass transition temperature (Tg)
- Drug melting point
Correct Answer: Drug molecular radius
Q5. Which solid-state property often increases apparent solubility and dissolution rate of a drug, benefiting controlled-release formulation?
- High crystallinity
- Amorphous form
- Higher melting point
- Polymorphic stability
Correct Answer: Amorphous form
Q6. In matrix-controlled release, which mechanism commonly governs drug release for poorly soluble drugs?
- Purely osmotic pumping
- Diffusion through swollen polymer pathways
- Immediate burst followed by zero-order
- Enzymatic cleavage only
Correct Answer: Diffusion through swollen polymer pathways
Q7. Which property is most critical when designing an oral osmotic pump tablet?
- Drug photostability
- Drug solubility in release medium
- Melting point of the drug
- Color of the tablet coating
Correct Answer: Drug solubility in release medium
Q8. The Higuchi model describes release from which type of system?
- Swelling-controlled erodible microparticles
- Matrix systems where release is diffusion controlled
- Pure osmotic systems with constant pressure
- First-order degradation of unstable drugs
Correct Answer: Matrix systems where release is diffusion controlled
Q9. Which of the following increases drug diffusion through a polymeric membrane?
- Increased polymer crosslink density
- Lower temperature below polymer Tg
- Smaller drug molecular size
- Higher drug crystallinity within matrix
Correct Answer: Smaller drug molecular size
Q10. Which physicochemical property affects drug distribution between aqueous and lipid phases and is critical for micelle- or liposome-based controlled delivery?
- Hydrogen bonding capacity only
- Partition coefficient (log P)
- Bulk density
- Optical rotation
Correct Answer: Partition coefficient (log P)
Q11. Ionization of a drug at physiological pH influences which two key formulation outcomes?
- Crystalline form and particle morphology
- Solubility and membrane permeability
- Melting point and glass transition temperature
- Polymorphic selection and color
Correct Answer: Solubility and membrane permeability
Q12. Which formulation approach can improve dissolution of a poorly soluble, highly crystalline drug for controlled-release formulation?
- Using a more hydrophobic polymer matrix
- Converting to amorphous solid dispersion
- Increasing tablet compression force only
- Choosing larger particle size
Correct Answer: Converting to amorphous solid dispersion
Q13. A high melting point drug is generally associated with which of the following that can slow dissolution?
- Higher aqueous solubility
- Stronger crystal lattice energy
- Increased bioavailability
- Better polymer compatibility
Correct Answer: Stronger crystal lattice energy
Q14. Which property should be minimized to reduce burst release from nanoparticle formulations?
- Surface-associated drug fraction
- Core hydrophobicity
- Polymer molecular weight
- Encapsulation efficiency
Correct Answer: Surface-associated drug fraction
Q15. Zeta potential of colloidal carriers primarily influences which aspect relevant to controlled delivery?
- Drug melting point
- Physical stability and aggregation tendency
- Chemical degradation rate of drug
- Polymer swelling index
Correct Answer: Physical stability and aggregation tendency
Q16. Which drug characteristic favors transdermal delivery and sustained systemic absorption?
- High molecular weight (>1000 Da)
- High lipophilicity with moderate aqueous solubility
- Strong acidity with pKa < 1
- Extensive hydrogen bonding capacity only
Correct Answer: High lipophilicity with moderate aqueous solubility
Q17. In polymeric controlled-release systems, increasing polymer hydrophilicity generally leads to:
- Decreased swelling and slower release
- Increased swelling and faster aqueous channel formation
- Lower drug solubility inside matrix
- Irreversible drug–polymer covalent bonding
Correct Answer: Increased swelling and faster aqueous channel formation
Q18. Which parameter is used to quantify a drug’s propensity to form hydrogen bonds and influences solubility and polymer interactions?
- Log P only
- Hydrogen bond donor/acceptor count and Hansen solubility parameters
- Bulk density
- Thermal conductivity
Correct Answer: Hydrogen bond donor/acceptor count and Hansen solubility parameters
Q19. For sustained release tablets, sink conditions during in vitro dissolution testing are important because:
- They accelerate polymer degradation
- They maintain a concentration gradient driving diffusion
- They prevent tablet swelling
- They cause drug recrystallization within matrix
Correct Answer: They maintain a concentration gradient driving diffusion
Q20. Which factor most directly affects the rate of drug release from biodegradable polymeric microparticles?
- Polymer molecular weight and degradation rate
- Tablet colorant
- Ambient light intensity
- Drug optical activity
Correct Answer: Polymer molecular weight and degradation rate
Q21. Which property of a drug would favor zero-order release from a reservoir device?
- Extremely high aqueous solubility exceeding sink capacity
- Sufficient solubility to maintain near-constant concentration in the reservoir
- Very large molecular weight preventing diffusion
- Complete instability in aqueous media
Correct Answer: Sufficient solubility to maintain near-constant concentration in the reservoir
Q22. Which of the following influences drug–polymer miscibility and can prevent phase separation in sustained-release formulations?
- Large differences in Hansen solubility parameters
- Close match of solubility parameters and favorable hydrogen bonding
- High drug crystallinity only
- Use of hydrophobic fillers exclusively
Correct Answer: Close match of solubility parameters and favorable hydrogen bonding
Q23. Which physical property contributes to particle uptake by cells and affects retention and release in nanoparticle delivery?
- Particle color
- Particle size and surface charge
- Drug melting point
- Tablet hardness
Correct Answer: Particle size and surface charge
Q24. The presence of multiple polymorphs of a drug can impact controlled release because polymorphs differ in:
- Optical rotation only
- Solubility, dissolution rate, and stability
- Color exclusively
- Electron configuration only
Correct Answer: Solubility, dissolution rate, and stability
Q25. Osmotic-controlled release systems rely primarily on which driving force for drug delivery?
- Polymer erosion
- Hydrostatic pressure gradient generated by osmotic influx
- Diffusion down a chemical potential gradient only
- Enzymatic cleavage
Correct Answer: Hydrostatic pressure gradient generated by osmotic influx
Q26. Which analytical parameter is most useful to assess permeability across Caco-2 cell monolayers for formulation screening?
- Apparent permeability coefficient (Papp)
- Melting enthalpy
- Glass transition temperature
- Refractive index
Correct Answer: Apparent permeability coefficient (Papp)
Q27. Which excipient property can be exploited to modulate drug release by altering matrix porosity after hydration?
- Non-swelling filler with zero solubility
- Hydrophilic pore former that dissolves to create channels
- Colorant stability
- High glass transition temperature polymer only
Correct Answer: Hydrophilic pore former that dissolves to create channels
Q28. In controlled release, what is the effect of increasing drug loading in a matrix if drug is poorly soluble?
- Always increases release rate linearly
- May create drug-rich domains reducing effective diffusion and causing burst
- Decreases risk of recrystallization
- Prevents polymer hydration
Correct Answer: May create drug-rich domains reducing effective diffusion and causing burst
Q29. Moisture uptake by a hygroscopic drug or excipient in a controlled-release tablet can cause:
- Improved thermal stability
- Changes in tablet porosity, accelerated release, and possible chemical degradation
- Permanent crystallization to more soluble form always
- Complete prevention of polymer swelling
Correct Answer: Changes in tablet porosity, accelerated release, and possible chemical degradation
Q30. Which strategy best improves bioavailability of a BCS Class II drug in a controlled-release oral formulation?
- Decrease surface area by increasing particle size
- Enhance dissolution via solid dispersion or surfactant incorporation while controlling release
- Use a completely hydrophobic coating to prevent dissolution
- Exclude any polymeric carrier
Correct Answer: Enhance dissolution via solid dispersion or surfactant incorporation while controlling release
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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