Amity Institute of Pharmacy

Advanced Biopharm and

pharmacokinetics

M. Pharm (II Sem)

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• Definition
• Objectives
• Different methods used for dissolution comparison
• Comparison of different methods
•

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• Dissolution Profile Comparison

• Definition: It is graphical representation [in terms of
concentration vs. time] of complete release of A.P.I. from a
dosage form in an appropriate selected dissolution medium.
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• To Develop in vitro-in vivo correlation which can help to reduced

costs, speed-up product development and reduced the need of
perform costly bioavailability human volunteer studies.
• To stabilize final dissolution specification for the pharmacological
dosage form
• Establish the similarity of pharmaceutical dosage forms, for
which composition, manufacture site, scale of manufacture,
manufacture process and/or equipment may have changed within
defined limits.
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• IMPORTANCE OF DISSOLUTION PROFILE 

• Dissolution profile of an A.P.I. reflects its release pattern under the
selected condition sets. i.e. either sustained release or immediate
release of the formulated formulas.
• For optimizing the dosage formula by comparing the dissolution
profiles of various formulas of the same A.P.I
• Dissolution profile comparison between pre change and post change
products for SUPAC (scale up post approval change ) related
changes or with different strengths, helps to assure the similarity in
the product performance and green signals to bioequivalence.
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• IMPORTANCE OF DISSOLUTION PROFILE

• FDA has placed more emphasis on dissolution profile comparison
in the field of post approval changes and biowaivers (e.g. Class I
drugs of BCS classification are skipped off these testing for
quicker approval by FDA ).
• The most important application of the dissolution profile is that
by knowing the dissolution profile of particular product of the
BRAND LEADER, we can make appropriate necessary change in
our formulation to achieve the same profile of the BRAND
LEADER.
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METHODS TO COMPARE DISSOLUTION PROFILE

1.Graphical
2.Statistical
3.Model Dependent
4.Model independent

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• Graphical method
• In this method we plot graph of Time V/S concentration of solute
(drug) in the dissolution medium or biological fluid.
• The shape of two curves is compared for comparison of dissolution
pattern and the concentration of drug at each point is compared for
extent of dissolution.
• If two or more curves are overlapping then the dissolution profile is
comparable.
• If difference is small then it is acceptable but higher differences
indicate that the dissolution profile is not comparable.
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• ANOVA method (ANALYSIS OF VARIENCE)

• This test is generally applied to different groups of data. Here
we compare the variance of different groups of data and predict
weather the data are comparable or not.
• Minimum three sets of data are required. Here first we have to
find the variance within each individual group and then
compare them with each other.

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• Model dependent methods

• 1) Zero order kinetics
• 2) First order kinetics
• 3)Hixon-Crowell
• 4)Higuchi Model
• 5) Korsmeyer-Peppas model

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• Model independent

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• The similarity factor (f2 ) as defined by FDA is logarithmic

reciprocal square root transformation of sum of squared error
and is a measurement of the similarity in the percentage (%)
dissolution between the two curves

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• Guidance for Industry

• A specific procedure to determine difference and similarity factors is as follows:
• Determine the dissolution profile of two products (12 units each) of the test (postchange) and
reference (prechange) products.
• Using the mean dissolution values from both curves at each time interval, calculate the difference
factor (f1 ) and similarity factor (f2) using the above equations.
• For curves to be considered similar, f1 values should be close to 0, and f2 values should be close to
100.
• Generally, f1 values up to 15 (0-15) and f2 values greater than 50 (50-100) ensure equivalence of the
two curves and thus, of the performance of the test (postchange) and reference (prechange) products.
• This model independent method is most suitable for dissolution profile comparison when three to four
or more dissolution time points are available.

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• The following recommendations should also be considered:

• The dissolution measurements of the test and reference batches should be made under exactly the
same conditions.
• The dissolution time points for both the profiles should be the same (e.g., 15, 30, 45, 60 minutes).
• The reference batch used should be the most recently manufactured prechange product.
• Only one measurement should be considered after 85% dissolution of both the products.
• To allow use of mean data, the percent coefficient of variation at the earlier time points (e.g., 15
minutes) should not be more than 20%, and at other time points should not be more than 10%.
• The mean dissolution values for R can be derived either from (1) last prechange (reference) batch or
(2) last two or more consecutively manufactured prechange batches.

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 Reference
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• Guidance for Industry Dissolution Testing of Immediate

Release Solid Oral Dosage Forms U.S. Department of Health
and Human Services Food and Drug Administration Center for
Drug Evaluation and Research (CDER), August-2011

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