Pharmacokinetics in NDDS development MCQs With Answer

Introduction:

This collection of MCQs on Pharmacokinetics in NDDS development is designed for M.Pharm students preparing for exams and practical applications in formulation and biological evaluation. The questions focus on ADME principles as applied to novel drug delivery systems (liposomes, nanoparticles, implants, inhalation, transdermal and depot systems), pharmacokinetic modeling, IVIVC, bioavailability enhancement strategies, lymphatic transport, and population and physiologically based PK approaches. Each question emphasizes mechanistic understanding and decision-making relevant to NDDS development, including sampling design, clearance considerations, and interpretation of non-linear kinetics. Answers are provided to aid rapid self-assessment and targeted revision for advanced coursework and research in drug delivery and pharmacokinetics.

Q1. Which pharmacokinetic parameter primarily determines the loading dose required to achieve a target plasma concentration for a drug incorporated into a sustained-release implant?

• Clearance
• Volume of distribution
• Bioavailability
• Elimination half-life

Correct Answer: Volume of distribution

Q2. In developing an oral lipid-based NDDS aimed at lymphatic absorption, which property of the drug most strongly favors intestinal lymphatic transport?

• High aqueous solubility and low log P
• High molecular weight (>500 Da) and polar surface area
• High lipophilicity (log P > 5) and long-chain triglyceride solubility
• Rapid enzymatic hydrolysis in the gut lumen

Correct Answer: High lipophilicity (log P > 5) and long-chain triglyceride solubility

Q3. For an NDDS that exhibits flip-flop kinetics, which statement is true?

• Apparent elimination rate is determined by rapid absorption and slow elimination.
• The observed terminal slope reflects the absorption rate constant, not the elimination rate constant.
• Bioavailability cannot be estimated from oral data.
• Flip-flop kinetics only occurs with intravenous administration.

Correct Answer: The observed terminal slope reflects the absorption rate constant, not the elimination rate constant.

Q4. A liposomal formulation reduces a drug’s apparent clearance in vivo. Which mechanism best explains this observation?

• Increased renal filtration due to smaller particle size
• Protection from metabolic enzymes and reduced free fraction in plasma
• Enhanced hepatic extraction due to opsonization
• Increased enterohepatic recirculation

Correct Answer: Protection from metabolic enzymes and reduced free fraction in plasma

Q5. Which in vitro–in vivo correlation (IVIVC) level is most suitable for NDDS with complex release mechanisms requiring deconvolution and population modeling?

• Level A (point-to-point correlation)
• Level B (statistical moment comparison)
• Level C (single-point correlation)
• No IVIVC possible for complex systems

Correct Answer: Level A (point-to-point correlation)

Q6. When applying physiologically based pharmacokinetic (PBPK) modeling for nanoparticles, which additional parameter is critical compared to small-molecule PBPK?

• Fraction unbound in plasma (fu)
• Particle size–dependent tissue uptake and MPS clearance rates
• Renal tubular secretion clearance
• pKa of the drug

Correct Answer: Particle size–dependent tissue uptake and MPS clearance rates

Q7. During development of a transdermal NDDS, which PK consideration is most important to minimize systemic accumulation during chronic dosing?

• Maximize Cmax regardless of dosing interval
• Ensure steady-state trough concentration is below toxic threshold via appropriate patch flux and dosing interval
• Design for immediate release to avoid depot formation in skin
• Avoid skin permeation enhancers to reduce local irritation

Correct Answer: Ensure steady-state trough concentration is below toxic threshold via appropriate patch flux and dosing interval

Q8. Which bioanalytical challenge is especially pertinent when measuring free drug concentration for highly protein-bound drugs delivered by NDDS?

• Matrix effects only in urine samples
• Artifactual displacement of drug from plasma proteins during sample processing
• Low sensitivity of LC-MS/MS for free drug
• Interference from liposomal phospholipids only in whole blood

Correct Answer: Artifactual displacement of drug from plasma proteins during sample processing

Q9. For a depot microsphere formulation intended for monthly release, which kinetic model is most appropriate for early development release profiling and correlation to plasma PK?

• Zero-order release model without mechanistic linkage
• Higuchi model for diffusion-controlled release combined with compartmental PK modeling
• Michaelis-Menten kinetics only
• Pure first-order release with no PK integration

Correct Answer: Higuchi model for diffusion-controlled release combined with compartmental PK modeling

Q10. In population pharmacokinetic (PopPK) analysis for an inhaled NDDS, which covariate is most likely to explain inter-individual variability in pulmonary absorption?

• Ambient humidity during sampling
• Patient inspiratory flow rate and inhalation technique
• Dietary fat content
• Urine pH

Correct Answer: Patient inspiratory flow rate and inhalation technique

Q11. A prodrug is incorporated into a nanoparticle to improve oral absorption. Which pharmacokinetic outcome indicates successful conversion and systemic exposure of the active moiety?

• High parent prodrug plasma levels with no active detected
• High systemic levels of the active form with improved bioavailability compared to prodrug alone
• Complete elimination of both prodrug and active form in feces
• Increased first-pass metabolism of the prodrug without active formation

Correct Answer: High systemic levels of the active form with improved bioavailability compared to prodrug alone

Q12. When establishing bioequivalence for a sustained-release NDDS, which PK metric is most critical in addition to AUC?

• Time to peak plasma concentration (Tmax) only
• Partial AUCs (e.g., AUC0–t for early and late phases) and Cmax as appropriate
• Only Cmin at steady state
• Urinary recovery regardless of systemic exposure

Correct Answer: Partial AUCs (e.g., AUC0–t for early and late phases) and Cmax as appropriate

Q13. Non-linear pharmacokinetics observed with an NDDS is often due to saturable processes. Which process is least likely to cause non-linearity for a nanoparticle-based formulation?

• Saturation of mononuclear phagocyte system (MPS) uptake
• Saturation of hepatic metabolic enzymes due to high local drug concentrations
• Saturation of renal glomerular filtration due to particle size increase
• Saturation of plasma protein binding sites

Correct Answer: Saturation of renal glomerular filtration due to particle size increase

Q14. Which sampling strategy is most appropriate to characterize both absorption and long-term elimination phases for a controlled-release injectable NDDS?

• Sparse sampling only at steady state
• Rich sampling early after dosing (to capture absorption) plus extended sparse sampling over weeks/months for elimination
• Single trough sample per dosing interval
• Only sampling during the first 24 hours post-dose

Correct Answer: Rich sampling early after dosing (to capture absorption) plus extended sparse sampling over weeks/months for elimination

Q15. An NDDS increases oral drug bioavailability by inhibiting P-gp efflux in the gut. Which pharmacokinetic effect would you expect?

• Decreased AUC and increased clearance
• Increased AUC and possibly increased Cmax due to higher intestinal absorption
• No change in systemic exposure but increased urinary excretion
• Reduced half-life due to enhanced hepatic extraction

Correct Answer: Increased AUC and possibly increased Cmax due to higher intestinal absorption

Q16. For a drug with high first-pass metabolism, which NDDS approach is likely to most effectively increase systemic bioavailability?

• Oral immediate-release tablet
• Sublingual or buccal mucoadhesive delivery to bypass hepatic first-pass
• Formulation increasing gastric residence time only
• Rectal suppository that releases only in the distal rectum

Correct Answer: Sublingual or buccal mucoadhesive delivery to bypass hepatic first-pass

Q17. Which PK/PD consideration is essential when designing a depot formulation for a narrow therapeutic index drug?

• Aiming for very high peak concentrations regardless of trough levels
• Achieving a predictable and controllable release rate to maintain concentrations within a narrow therapeutic window
• Maximizing variability between patients to ensure some receive higher doses
• Minimizing monitoring because depot ensures safety

Correct Answer: Achieving a predictable and controllable release rate to maintain concentrations within a narrow therapeutic window

Q18. During PK evaluation of a nanocarrier delivering a hydrophilic drug, total drug concentration remains high but free drug is low. What implication does this have for PD effect?

• High PD effect is guaranteed because total drug is high
• PD effect may be reduced because only free drug is pharmacologically active
• Protein binding always increases PD effect
• Free drug concentration is irrelevant for nanocarriers

Correct Answer: PD effect may be reduced because only free drug is pharmacologically active

Q19. Which statistical approach is most appropriate for handling below-limit-of-quantification (BLQ) PK data during modeling of long-acting NDDS?

• Exclude all BLQ data from analysis without consideration
• Use censored data methods such as M3 method in NONMEM to appropriately handle BLQ observations
• Replace BLQ values with zero and proceed
• Replace BLQ values with LLOQ/2 and ignore uncertainty

Correct Answer: Use censored data methods such as M3 method in NONMEM to appropriately handle BLQ observations

Q20. In designing an IVIVC for a nanoparticulate sustained-release formulation, which in vitro test modification improves predictability of in vivo release?

• Performing release in pure water at room temperature only
• Using biorelevant media, agitation and sink/non-sink conditions that mimic physiological environment
• Measuring only initial burst release in static conditions
• Excluding surfactants to prevent micelle formation

Correct Answer: Using biorelevant media, agitation and sink/non-sink conditions that mimic physiological environment

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