The primary constraint for comparison of two products or formulations or dosage forms is the in vitro dissolution profile. For comparison of in vitro dissolution profiles, similarity and difference factors are emphasized by US FDA.

**Similarity Factor (f2) ^{1, 2, 3}: **

As the name specifies, it stresses on the comparison of closeness of two comparative formulations.Generally similarity factor in the range of 50-100 is acceptable according to US FDA. It can be computated using the formula

f2= 50xlog {[1+ (1/n) S _{t=}_{1}^{n} (R_{t}-T_{t}) ^{2}] ^{-0.5 }x100}........(1)

where, n is the number of dissolution sample times,

R_{t} and T_{t} are the individual or mean percent dissolved at each time point, t, for the reference and test dissolution profiles, respectively.

The similarity factor should be between 0 and 100. It is 100 when two comparative groups of reference and test are identical and approaches 0 as the dissimilarity increases.

**Difference Factor (f1) ^{1, 2}:**

Difference factor focuses on the difference in percent dissolved between reference and test at various time intervals. It can be mathematically computed by using

f1= {[S _{t=}_{1}^{n} |R_{t}-T_{t}|] / [S _{t=}_{1}^{n}^{ }R_{t}]} x100................(2)

Therefore the factors directly compare the difference between percent drug dissolved per unit time for a test and a reference product.

US FDA included the f1, f2 factors in various guidance documents and stated different criterias for dissolution profile comparison as ^{4, 5}

1. The dissolution profiles can be compared only when number of dissolution units used are equal to or greater than 12. The similarity factor should be computed from the average mean dissolution data of 12 units. The mean data for comparison can be used only if the coefficient of variation at the first time point is NMT 20%, and NLT 10% at the rest of time intervals.

2. For accurate calculation of similarity factor, statistical approach of establishment of confidence intervals, to determine whether the reference and test are statistically significant or not may be used.

3. The dissolution conditions should be identical for both reference and test products (example the strength of dosage form, test time intervals, temperature, rpm, total test time etc).

4. The literature also states to consider only one time after 85% dissolution of product, since f2 values are sensitive to number of dissolution time points.

5. For rapid dissolving products, that may dissolve 85% in 15 minutes, comparison of dissolution profiles is not mandatory.

6. Similarity factor of 50-100 ensures sameness of two products

7. Difference factor of 0-15 ensures minor difference between two products.

Prior to in vivo study, comparison of in vitro dissolution profiles using similarity and difference factors may be the promising surrogate.

**References:**

**1.** Yuksel N, Kanik AE, Baykara T, Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and -independent methods, Int J Pharm, 209, 2000, 57-67.

**2**. Costa P & Jose MSL, Modeling and comparison of dissolution profiles, Eur J Pharm Sci, 13, 2001, 123-133.

**3**. Ocana J, Frutos G & Sanchez O P, Using the similarity factor f2 in practice: A critical revision and suggestions for its standard error estimation, Chemometrics and Intelligent Laboratory Systems, 99, 2009, 49-56.

**4.** Costa P, An alternative method to the evaluation of similarity factor in dissolution testing, Int J Pharm, 220, 2001, 77-83.

**5. **O Hara T, Dunne A, Butler J & Devane J, A review of methods used to compare dissolution profile data, Pharmaceutical Science & Technology Today, 1(5), 1998, 214-223.

**"This book page doesn't include any plagiarized material"**

**Abbreviations:**

NMT - Not more than

NLT - Not less than

## Comments

Niklesh Rao V

Thu, 08/19/2010 - 15:49

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## Quite a brief summary of the

Regards, Niklesh Rao V

P.V.ABHIGNA

Sat, 08/21/2010 - 16:38

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## Simple and short.....

ABHIGNA.P.V.

Amol Malpani

Sat, 08/21/2010 - 17:19

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## Why f1 factor

Amol S Malpani

Second prize Winnersof Skills Test 2010

TK Indira

Wed, 08/25/2010 - 07:21

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## Dear amol sir

T.K. Indira. http://www.pharmainfo.net/tkindira

--

"Our greatest glory is not in never falling, but in rising every time we fall..."Team 'Char'minar.Amol Malpani

Fri, 08/27/2010 - 20:39

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## YA that what I expect

Amol S Malpani

Second prize Winnersof Skills Test 2010

Duli Chand Rohilla

Wed, 02/16/2011 - 07:43

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## Good knowledge for initial stage

Dulichand