Design approaches based on diffusion-controlled release are fundamental for B. Pharm students learning sustained and controlled drug delivery. This introduction covers matrix and reservoir strategies, Fick’s laws, the Higuchi model, diffusivity, partitioning, polymeric carriers, and practical factors—solubility, porosity, swelling, crosslinking, and drug loading—that govern release kinetics. It also explains model selection (Higuchi, Korsmeyer–Peppas), experimental tools (Franz diffusion cell), and formulation tactics (hydrophilic matrices, coated multiparticulates, microencapsulation) for predictable performance. Emphasis on assumptions, limitations, optimization, and regulatory considerations helps students design robust oral, topical, or implantable systems. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What best defines a diffusion-controlled drug release mechanism?
- Drug release governed primarily by the movement of drug molecules through a polymer or porous structure
- Drug release determined only by dissolution of the drug in the medium
- Drug release controlled only by enzymatic degradation of the polymer
- Drug release caused by osmotic pressure without diffusion
Correct Answer: Drug release governed primarily by the movement of drug molecules through a polymer or porous structure
Q2. Which statement correctly distinguishes a matrix system from a reservoir system?
- Matrix system: drug dispersed throughout a polymer; reservoir system: drug contained in a core surrounded by a rate-controlling membrane
- Matrix system always gives zero-order release; reservoir system always gives first-order release
- Matrix systems are only used for parenteral delivery; reservoir systems are only oral
- Matrix systems require osmotic gradients; reservoir systems do not
Correct Answer: Matrix system: drug dispersed throughout a polymer; reservoir system: drug contained in a core surrounded by a rate-controlling membrane
Q3. The Higuchi model predicts cumulative drug release is proportional to which mathematical function of time?
- Square root of time (t^0.5)
- Logarithm of time (ln t)
- Time squared (t^2)
- Exponential of time (e^t)
Correct Answer: Square root of time (t^0.5)
Q4. Which combination lists core assumptions of the classical Higuchi model?
- Initial drug concentration in matrix >> drug solubility, constant diffusion coefficient, perfect sink conditions, no matrix swelling or dissolution
- Drug uniformly dissolves in release medium without concentration gradient and matrix totally erodes immediately
- Diffusion coefficient varies strongly with concentration and medium is non-sink
- Matrix swells and fully dissolves during drug release with significant convective flow
Correct Answer: Initial drug concentration in matrix >> drug solubility, constant diffusion coefficient, perfect sink conditions, no matrix swelling or dissolution
Q5. Fick’s first law describes which physical quantity in diffusion-controlled release?
- Steady-state flux proportional to concentration gradient
- Time-dependent change of concentration in the matrix
- Partitioning of drug between two immiscible phases
- Overall drug dissolution rate in the bulk medium
Correct Answer: Steady-state flux proportional to concentration gradient
Q6. Fick’s second law is applied to describe which situation?
- Non-steady-state (time-dependent) diffusion within a matrix or membrane
- Instantaneous equilibrium partitioning at an interface
- Zero-order release from a perfect reservoir
- Mechanical erosion-driven release only
Correct Answer: Non-steady-state (time-dependent) diffusion within a matrix or membrane
Q7. In the Korsmeyer–Peppas model for a thin slab, an exponent n ≈ 0.5 indicates which release mechanism?
- Fickian diffusion-controlled release
- Purely swelling-controlled (Case II) transport
- Super case II transport dominated by erosion
- Immediate burst release with no diffusion control
Correct Answer: Fickian diffusion-controlled release
Q8. Which polymer property most directly reduces effective diffusivity of a drug in a solid polymer matrix?
- High degree of crosslinking
- Low molecular weight of polymer chains
- High polymer hydration capacity only
- Bright polymer color
Correct Answer: High degree of crosslinking
Q9. The partition coefficient (K) between drug and polymer affects diffusion-controlled release by:
- Dictating the drug concentration at the polymer–medium interface and thus the driving force for diffusion
- Only affecting the mechanical strength of the dosage form
- Controlling the ionic strength of the release medium
- Changing the polymer glass transition temperature directly
Correct Answer: Dictating the drug concentration at the polymer–medium interface and thus the driving force for diffusion
Q10. What is meant by “sink conditions” in diffusion experiments?
- The release medium volume and removal maintain drug concentration near zero so it does not limit diffusion
- The experiment is performed in an anaerobic chamber
- The drug concentration in the matrix equals that in the release medium
- The membrane used has no pores
Correct Answer: The release medium volume and removal maintain drug concentration near zero so it does not limit diffusion
Q11. Which experimental apparatus is commonly used for measuring membrane permeation and diffusion-controlled release in topical and transdermal studies?
- Franz diffusion cell
- USP disintegration apparatus
- Atomic absorption spectrometer
- Gel permeation chromatography
Correct Answer: Franz diffusion cell
Q12. The initial burst release from a matrix system is most often caused by:
- Drug located on or near the surface and loosely associated with the matrix
- Complete crosslinking of the polymer network
- Low drug solubility in release medium only
- Perfectly impermeable coatings
Correct Answer: Drug located on or near the surface and loosely associated with the matrix
Q13. Which formulation strategy is most effective to reduce an undesirable initial burst in diffusion-controlled systems?
- Applying a diffusion-controlling coating or entrapping drug deeper within the matrix
- Decreasing polymer molecular weight drastically
- Adding a brightly colored dye
- Reducing the total batch mixing time only
Correct Answer: Applying a diffusion-controlling coating or entrapping drug deeper within the matrix
Q14. Which polymer is commonly used as a hydrophilic matrix former for sustained oral release?
- Hydroxypropyl methylcellulose (HPMC)
- Polyethylene glycol with no modification
- Starch only used in immediate release
- Polyvinyl chloride (PVC)
Correct Answer: Hydroxypropyl methylcellulose (HPMC)
Q15. Reservoir-type diffusion-controlled devices most commonly aim to achieve which release profile?
- Approximate zero-order (constant rate) release when membrane resistance is rate-limiting
- Immediate first-order burst release only
- Complete release within 5 minutes always
- No release until polymer degrades fully
Correct Answer: Approximate zero-order (constant rate) release when membrane resistance is rate-limiting
Q16. The original Higuchi equation was derived for which geometry of matrix?
- Planar (slab) matrix geometry
- Perfect sphere with convective flow
- All geometries equally without modification
- Hollow cylinders only
Correct Answer: Planar (slab) matrix geometry
Q17. A constant concentration gradient across a membrane is expected to produce which type of release rate?
- Zero-order (constant) release
- Exponential increase in release
- Logarithmic decay of release
- Release only upon mechanical agitation
Correct Answer: Zero-order (constant) release
Q18. How does increased polymer crystallinity typically affect drug diffusivity?
- It decreases diffusivity by reducing free volume and segmental mobility
- It increases diffusivity by creating more pathways
- It has no effect on diffusivity
- It makes the drug chemically react and disappear
Correct Answer: It decreases diffusivity by reducing free volume and segmental mobility
Q19. Which effect does increased porosity of a matrix usually have on diffusion-controlled drug release?
- Increases release rate by providing additional pathways for solvent infiltration and diffusion
- Eliminates diffusion and makes release purely erosion-controlled
- Always causes complete inertness and no release
- Decreases release rate by blocking pores
Correct Answer: Increases release rate by providing additional pathways for solvent infiltration and diffusion
Q20. The role of a plasticizer in a diffusion-controlled polymer matrix is to:
- Increase chain mobility and thus often increase drug diffusivity and release rate
- Completely immobilize polymer chains to prevent any release
- Change drug chemistry to a new active compound
- Only alter the color without affecting release
Correct Answer: Increase chain mobility and thus often increase drug diffusivity and release rate
Q21. Which description best characterizes a swelling-controlled delivery system?
- Polymer hydrates to form a gel layer; drug diffuses through this dynamic gel barrier
- Drug instantly dissolves in the medium and is removed
- Polymer dissolves immediately leaving no control
- Release is controlled exclusively by osmotic pressure without polymer involvement
Correct Answer: Polymer hydrates to form a gel layer; drug diffuses through this dynamic gel barrier
Q22. The Korsmeyer–Peppas model is most useful when:
- The mechanism of release is not well characterized and multiple processes may contribute
- The release mechanism is perfectly known and purely zero-order
- Only chemical degradation controls release
- There is no mathematical relation between release and time
Correct Answer: The mechanism of release is not well characterized and multiple processes may contribute
Q23. Which plot gives a straight line when the Higuchi model is applicable?
- Cumulative drug released per unit area (Q) versus square root of time (t^0.5)
- Log cumulative release versus time
- Cumulative release versus ln(time)
- Release rate versus inverse time
Correct Answer: Cumulative drug released per unit area (Q) versus square root of time (t^0.5)
Q24. In a reservoir diffusion system which step is typically rate-limiting?
- Diffusion of drug through the rate-controlling membrane
- Rapid dissolution of drug in the core only
- Immediate convective mixing in surrounding medium
- Color change of the reservoir
Correct Answer: Diffusion of drug through the rate-controlling membrane
Q25. Which of the following is least likely to affect diffusion-controlled release from a polymer matrix?
- Particle color
- Drug solubility
- Polymer molecular weight
- Matrix porosity
Correct Answer: Particle color
Q26. How does temperature generally affect the diffusion coefficient of a drug in a polymer matrix?
- Diffusion coefficient increases with temperature, often following an Arrhenius relationship
- Temperature has no effect on diffusion
- Diffusion coefficient decreases linearly with increasing temperature
- Diffusion stops entirely above 20°C
Correct Answer: Diffusion coefficient increases with temperature, often following an Arrhenius relationship
Q27. Under perfect sink boundary conditions at the external surface, the drug concentration in the release medium at the interface is assumed to be:
- Negligibly small or effectively zero
- Equal to the drug concentration inside the matrix
- Constant and equal to the drug’s saturation in the matrix
- Greater than saturation concentration always
Correct Answer: Negligibly small or effectively zero
Q28. Which microencapsulation technique is commonly used to prepare diffusion-controlled polymer-coated microparticles?
- Solvent evaporation (oil-in-water or water-in-oil) methods
- Simple mechanical compression without solvent
- Direct thermal fusion at 500°C
- Purely ionic colorimetric trapping
Correct Answer: Solvent evaporation (oil-in-water or water-in-oil) methods
Q29. In the Higuchi plot, the slope of Q versus sqrt(t) is most directly related to which formulation parameter?
- Effective diffusivity (D) and drug solubility terms combined in the Higuchi constant
- Polymer melting point exclusively
- The optical density of the matrix only
- The swelling index unrelated to diffusivity
Correct Answer: Effective diffusivity (D) and drug solubility terms combined in the Higuchi constant
Q30. For modified release products governed by diffusion, which level of in vitro–in vivo correlation (IVIVC) is most informative for predicting plasma profiles?
- Level A (point-to-point correlation) is most informative and desirable
- Level C (single point correlation) always suffices
- There is no value in any IVIVC for diffusion systems
- Random correlation with no mechanistic basis is preferred
Correct Answer: Level A (point-to-point correlation) is most informative and desirable
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