In-vitro – in-vivo correlation (IVIVC) MCQs With Answer

Introduction: In-vitro–in-vivo correlation (IVIVC) is a predictive scientific approach that links in vitro dissolution data with in vivo bioavailability and pharmacokinetic responses. IVIVC concepts — including Level A, B, and C correlations, deconvolution, Wagner–Nelson and Loo–Riegelman methods — are central to biopharmaceutics and formulation development. Mastery of IVIVC helps B. Pharm students understand bioavailability, dissolution testing, predictive modeling, regulatory pathways (FDA guidance), and biowaivers. Key keywords: IVIVC, dissolution, bioavailability, deconvolution, predictive model, FDA, BCS, discriminating dissolution, pharmacokinetics. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary goal of establishing an IVIVC?

• To determine drug toxicity in animals
• To link in vitro dissolution to in vivo bioavailability and predict plasma profiles
• To replace clinical trials for safety assessments
• To measure tablet hardness and friability

Correct Answer: To link in vitro dissolution to in vivo bioavailability and predict plasma profiles

Q2. Which of the following best describes a Level A IVIVC?

• A single-point correlation between one dissolution time and one PK parameter
• A statistical correlation of mean dissolution rates only
• A point-to-point relationship between in vitro dissolution and in vivo input rate over time
• A correlation using only Cmax values

Correct Answer: A point-to-point relationship between in vitro dissolution and in vivo input rate over time

Q3. Which IVIVC level provides the highest predictive confidence for in vivo performance?

• Level C
• Level B
• Level A
• Level D

Correct Answer: Level A

Q4. Which method is commonly used to estimate the fraction of drug absorbed for a one-compartment model?

• Loo–Riegelman method
• Wagner–Nelson method
• Numerical convolution
• Noncompartmental AUC ratio

Correct Answer: Wagner–Nelson method

Q5. The Loo–Riegelman method is specifically applied for which pharmacokinetic situation?

• Zero-order absorption only
• One-compartment models with linear elimination
• Two-compartment models for oral absorption
• Intravenous bolus dosing exclusively

Correct Answer: Two-compartment models for oral absorption

Q6. Which approach is model-independent for deconvolution in IVIVC?

• Compartmental regression
• Wagner–Nelson
• Loo–Riegelman
• Numerical deconvolution

Correct Answer: Numerical deconvolution

Q7. According to regulatory guidance, an acceptable average percent prediction error (PE) for internal validation of IVIVC for AUC and Cmax is generally:

• ≤5%
• ≤10%
• ≤25%
• ≤50%

Correct Answer: ≤10%

Q8. In constructing an IVIVC, which pair is typically plotted to build the correlation?

• Fraction absorbed (Fa) versus plasma clearance (CL)
• Fraction dissolved (Fd) versus fraction absorbed (Fa)
• Dose versus elimination half-life
• Cmax versus time to peak only

Correct Answer: Fraction dissolved (Fd) versus fraction absorbed (Fa)

Q9. Which of the following dissolution apparatus is most commonly used for oral solid dosage IVIVC studies?

• USP Apparatus 7 (reciprocating cylinder)
• USP Apparatus 2 (paddle)
• USP Apparatus 4 (flow-through cell) only
• Microscale dissolution viewer

Correct Answer: USP Apparatus 2 (paddle)

Q10. What is meant by “sink conditions” in dissolution testing?

• When the dissolution vessel is stirred at maximum speed
• When drug concentration in medium is less than about 10–15% of its saturation solubility
• When the tablet sinks to the bottom and does not float
• When pH is maintained at neutral

Correct Answer: When drug concentration in medium is less than about 10–15% of its saturation solubility

Q11. Noyes–Whitney equation is primarily used to describe which phenomenon?

• Plasma protein binding
• Dissolution rate of solid particles
• Hepatic metabolism kinetics
• Renal clearance mechanisms

Correct Answer: Dissolution rate of solid particles

Q12. Which Biopharmaceutics Classification System (BCS) class is most likely suitable for developing a successful IVIVC?

• 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 II (low solubility, high permeability)

Q13. Which factor most directly reduces the reliability of an IVIVC?

• Linear pharmacokinetics over the studied dose range
• Presence of extensive first-pass metabolism or enterohepatic recirculation
• Using discriminating dissolution conditions
• High in vivo permeability

Correct Answer: Presence of extensive first-pass metabolism or enterohepatic recirculation

Q14. Which metric quantifies the accuracy of predicted pharmacokinetic parameters from IVIVC?

• Percent prediction error (PE)
• Tablet disintegration time
• Potentiometric titration result
• Micromeritics index

Correct Answer: Percent prediction error (PE)

Q15. Level C IVIVC typically correlates which of the following?

• Entire plasma concentration–time profile point-by-point
• Single pharmacokinetic parameters such as Cmax or AUC with a dissolution metric
• Multiple timepoint profiles using deconvolution
• None; Level C is not used in IVIVC

Correct Answer: Single pharmacokinetic parameters such as Cmax or AUC with a dissolution metric

Q16. A multiple Level C IVIVC differs from single-point Level C by:

• Using only one dissolution time point
• Correlating several PK parameters (e.g., Cmax and AUC) with dissolution
• Being equivalent to Level A
• Using animal data only

Correct Answer: Correlating several PK parameters (e.g., Cmax and AUC) with dissolution

Q17. Which statistical parameter is most commonly reported to describe the goodness-of-fit for an IVIVC regression?

• Pearson correlation coefficient (r)
• Coefficient of determination (r²)
• Standard dissolution variance
• Tablet tensile strength

Correct Answer: Coefficient of determination (r²)

Q18. Which in vitro condition enhances the predictive value of dissolution for IVIVC?

• Non-discriminating media that dissolve all formulations identically
• Discriminating dissolution conditions that detect formulation differences
• Using no agitation to simulate stagnant GI tract
• Using extreme pH values only

Correct Answer: Discriminating dissolution conditions that detect formulation differences

Q19. Deconvolution in IVIVC is primarily used to:

• Estimate the drug input or absorption rate from plasma concentration data
• Predict tablet compressibility
• Calculate dissolution apparatus paddle speed
• Measure drug purity

Correct Answer: Estimate the drug input or absorption rate from plasma concentration data

Q20. Which practical application can IVIVC support in regulatory submissions?

• Requesting biowaivers for certain post-approval formulation changes
• Eliminating safety studies for new chemical entities
• Replacing all clinical trials for efficacy
• Predicting excipient toxicity

Correct Answer: Requesting biowaivers for certain post-approval formulation changes

Q21. For a drug with dissolution-limited absorption, which in vitro–in vivo relationship is expected?

• Weak or no correlation between dissolution and absorption
• Strong correlation because in vivo absorption is controlled by dissolution
• Absorption solely controlled by hepatic clearance
• Dissolution independent of formulation factors

Correct Answer: Strong correlation because in vivo absorption is controlled by dissolution

Q22. Which in vitro measure is most often used as the independent variable when establishing IVIVC?

• Percentage of drug dissolved over time (dissolution profile)
• Tablet hardness number
• Melting point of the API
• pH of the gastric fluid only

Correct Answer: Percentage of drug dissolved over time (dissolution profile)

Q23. Which software/approach is commonly used for pharmacokinetic deconvolution and IVIVC modeling?

• WinNonlin (Phoenix) or equivalent PK modeling software
• Microsoft Excel without any statistical tools
• Photo editing software
• Mass spectrometry only

Correct Answer: WinNonlin (Phoenix) or equivalent PK modeling software

Q24. Biorelevant dissolution media are used in IVIVC studies to simulate which conditions?

• In vitro heating profiles
• Fed and fasted gastrointestinal environments
• Sterile intravenous conditions
• Topical skin conditions

Correct Answer: Fed and fasted gastrointestinal environments

Q25. Which experimental prerequisite improves the quality of IVIVC data?

• Using a single in vivo profile from one subject only
• Collecting sufficiently dense plasma sampling during absorption phase
• Omitting assay validation for plasma concentrations
• Using non-discriminatory dissolution media

Correct Answer: Collecting sufficiently dense plasma sampling during absorption phase

Q26. Which type of drug absorption scenario makes a simple IVIVC less likely to succeed?

• Absorption limited strictly by dissolution
• High permeability and dose-independent kinetics
• Transporter-mediated uptake or saturable absorption
• Linear first-order absorption

Correct Answer: Transporter-mediated uptake or saturable absorption

Q27. In IVIVC terminology, the term “fraction absorbed (Fa)” refers to:

• The percentage of the dose that dissolves in vitro
• The cumulative fraction of drug that reaches systemic circulation over time
• The percent of excipient in the formulation
• The fraction of drug that remains undissolved

Correct Answer: The cumulative fraction of drug that reaches systemic circulation over time

Q28. Which experimental design choice can strengthen IVIVC development?

• Testing multiple formulation strengths and dissolution conditions
• Using only one formulation and one dissolution condition
• Avoiding replicate in vivo studies
• Using unrelated animal species only

Correct Answer: Testing multiple formulation strengths and dissolution conditions

Q29. Which statement about Level A IVIVC is TRUE?

• It only correlates a single time point like Cmax
• It can predict the entire plasma profile from in vitro dissolution
• It is the least informative level of correlation
• It cannot be used to support biowaivers

Correct Answer: It can predict the entire plasma profile from in vitro dissolution

Q30. Which outcome is a practical benefit of a validated IVIVC for a marketed product?

• Inability to change manufacturing without new studies
• Setting clinically relevant dissolution specifications and justifying formulation changes without new bioequivalence studies
• Immediate removal of all stability testing
• Requirement for additional invasive sampling in patients

Correct Answer: Setting clinically relevant dissolution specifications and justifying formulation changes without new bioequivalence studies

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