Dissolution Profile Comparison: F1 and F2 Calculation in Excel

In dissolution testing, f1 difference and f2 similarity calculations are used to compare one formulation to another or a test batch to a reference batch. This approach is useful to ensure that two formulations have similar bioavailability, which is important for ensuring that the therapeutic effect of the drug product remains consistent. By comparing products side by side, f1 and f2 calculations can provide assurance that both products are suitable for use in clinical trials or final market release.

The difference factor (f1) assesses the relative error between two dissolution curves at any given time point and is calculated as the percentage of discrepancy between them. The similarity factor (f2) is a measurement of the similarity in the percent (%) dissolution between two dissolution curves.

How to determine the difference (f1) and similarity (f2) factors:

1. Determine the dissolution profile of the test and reference products (12 units each).

2. Calculate the difference (f1) and similarity factor (f2) based on the mean dissolution values from both curves using the formulas below:

3. The following recommendations should also be considered:

• To ensure accurate comparison, the dissolution measurements for both test and reference batches should be taken in identical conditions. It is essential to use the same time points (e.g. 15, 30, 45, 60 min) throughout the procedure.

• Only one measurement after 85% dissolution should be included for both the test and reference batches.

• To utilize the mean data, the percent coefficient of variation for earlier time points (ex. 15 minutes) must not exceed 20%, and at the later time points, it should be less than 10%.

Generally, for curves to be considered similar, f1 values should be close to 0 and f2 values should be close to 100. The acceptance range for sameness or equivalence are:

• f1 between 0 -15

• f2 between 50 - 100

f1 and f2 Calculator Preview

Related Article: How to Use the f1 and f2 Dissolution Calculator.

Do you have any questions or suggestions? Feel free to reach us by clicking here.

Frequently Asked Questions

• What are f1 and f2 factors in dissolution testing?

  f1 (difference factor) and f2 (similarity factor) are model-independent statistical tools used to compare dissolution profiles between a test product and a reference product. They help determine whether two formulations release drug at a similar rate.

• Why are f1 and f2 calculations important?

  These calculations are important because they:

  • Compare test vs reference drug release 

  • Support bioequivalence assessments 

  • Ensure consistent product performance 

  • Help in regulatory submissions and post-change evaluations

• What does the f1 (difference factor) measure?

  The f1 factor measures the percentage difference between two dissolution profiles at each time point.
  It reflects how much the test product deviates from the reference product. 

  A lower f1 value indicates higher similarity.

• What does the f2 (similarity factor) measure?

  The f2 factor measures the similarity between two dissolution profiles using a logarithmic transformation of the squared differences between curves. 

  A higher f2 value indicates greater similarity.

• What are the acceptable limits for f1 and f2?

  0≤f1≤15

  50≤f2≤100

  If these conditions are met, the dissolution profiles are generally considered similar.

• How many units are used for f1 and f2 calculations?

  Typically:

  • 12 units for the test product 

  • 12 units for the reference product 

  Mean dissolution values are used for comparison.

• How many time points are required?

  At least:

  • 3 or more dissolution time points (excluding time zero) 

  • Same sampling times must be used for both products

• Can more than one value above 85% dissolution be used?

  No. Only one time point above 85% dissolution should be included for each profile in the f2 calculation.

• Why is the 85% dissolution rule important?

  It prevents over-weighting late-stage dissolution data, which could distort similarity comparisons between products.

• What variability limits are required for valid f2 calculation?

  For reliable results:

  • Early time points: %CV should be ≤ 20% 

  • Later time points: %CV should be ≤ 10%

• What does an f2 value of 100 mean?

  An f2 value of 100 indicates that the two dissolution profiles are identical.

• What does an f2 value below 50 mean?

  An f2 value below 50 indicates that the dissolution profiles are not similar.

• When is f2 not required?

  f2 calculation is generally not required when:

  • Both products dissolve very rapidly (≥85% within 15 minutes)

• What is the formula for f2?

  f2=50log⁡101001+1nt=1n(Rt-Tt)2
  Where:

  • Rt = reference dissolution at time t 

  • Tt = test dissolution at time t 

  • n = number of time points 

Get free pharmaceutical analytical calculation examples, Excel tools, and articles delivered to your inbox.