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I would like to know, for evaluation of dissolution profiles
similarity of
1) Refrence & Test product which would be tested for BE studies
2) Amonst the strength of same product. (Viz strength with proportional
compositions of Active & Excipients)
Which methods to be used.
Normally we use calculation of Similarity factor viz F1 & F2 as per FDA
Guide lines of Dissolution testing of IR solid dosage forms.
Is there is any othor method apart from this which can be used for
comparision of Dissolution profile similarity ?
Regards
Mahesh M. Samarth
M. Pharm, Ph.D.(Tech)
National Pharmaceutical Industries
P.O. 120, P.C. 124
Sultanate Of Oman
Email mahesh.-at-.npioman.com
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The following message was posted to: PharmPK
Smilarity Factor ( F2) is the one way of comparing the dissolution
profiles .The guiding principles says -F2 sould be more than 50% (
Means not more than 10% difference in the profiles).The similarity
factor calculation is very useful but the time points to be selected
carefully to avoid errors ( Over estimation). Normally for IR products
not more than one time points to be considered after 85% of the drug is
dissolved as it gives false estimation of the F2 if at termial phase
more points are considered after quantitative release ( 85%).Totally
atleast three time points to be considered. if the test and reference
products both shows more than 85% dissolution at 15 mins interval in
all media ( 1.2,4.5,6.8 and water etc.) then F2 determination is not
required as formulations will be considered Rapidly dissolving .
This comparison is to be done in different media and a discriminatory
media is to be identified by varying the rpm, media volume , pH ,ionic
strength etc. that can best reflect the effect of formulation variable
on dissolution and can eventually be used for IVIVC establishment.
This comparison is to be submitted for all strengths of the dose
proportional formulations even if a biowaiver is requested for lower
strengths.
regards,
Pradeep Bhadauria
RANBAXY RESEARCH LABORATORIES,
INDIA.
=
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The following message was posted to: PharmPK
In addition to the points made by Pradeep, more criteria need to be met
(ideally) in order for the f2 similarity factor calculations to be used
to
determine bioequivalent batches. The link to the FDA Guidance that
covers
these points is:
http://www.fda.gov/cder/guidance/1713bp1.pdf
Best regards,
Stephan
Stephan R. Ortiz, R.Ph., Ph.D.
Clinical Pharmacologist, Clinical Pharmacology & Biopharmaceutics
FDA/CDER/OCPB
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Pradeep,
Thanks for your comments regarding F2. I am working on non-standard
dosages, and would like to apply the F tests to them. What do you mean
regarding "over estimation" error from selecting time points?
Frank
Frank Bales, Ph.D.
Senior Regulatory Consultant
Worldwide Regulatory Affairs
PAREXEL Intl.
2520 Meridian Pkwy, Suite 200
Durham, NC 27713
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The following message was posted to: PharmPK
Frank,
In making these calculations, one should include no more than 1 point
beyond
90% dissolved. A quick example will probably best serve to illustrate
the
point.
The following will be %dissolved for both test and reference for time
points
10, 20, 30, 40, 50, 60 and 90 min.
Test: 35, 57, 86, 92, 94, 96, 99
Ref: 55, 70, 80, 90, 92, 94, 99
If all points are used, f2 = 51
If only first 4 points are used (no more than 1 point beyond 90%), f2 =
45
The more points used beyond 90%, the greater the similarity between the
batches. However, we're only concerned that the earlier points show
similar
dissolution profiles.
Hope this helps. Best regards.
Stephan
Stephan R. Ortiz, R.Ph., Ph.D.
Clinical Pharmacologist, Clinical Pharmacology & Biopharmaceutics
FDA/CDER/OCPB/DPEII
5600 Fishers Lane, HFD 870 (PKLN 18B-06)
Rockville, MD 20857
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The following message was posted to: PharmPK
Dear all,
To avoid problems with the method based on
the f2 factor, one can use the method proposed in our recent study:
Dedik L., Durisova M.: System-approach methods
for modeling and testing similarity of in vitro dissolutions
of drug dosage formulations. Comput. Meth. Programs Biomed.,
69, 2002, 49-55. The full text of the given study is available online
via Science Direct.
The proposed method enables to test also similarity of
dissolution rates of test and reference batches (as functions of
time).
The given study exemplifies the proposed method using dissolution data
taken
form a literature source and it also compares the results obtained by
the
proposed method with those obtained by the method based on the f2
factor.
Additionally, the given study discusses the cons and pros of the
method based on f2 factor and the cons and pros of the proposed method.
Last week we presented the method proposed in the given study
at the AAPS/FIP Regulatory Workshop bioequivalence and dissolution
in Bucharest. Dr. V.P. Shah took part in this workshop.
Regards,
Maria Durisova PhD, DrSc (Math/Phys)
Head of Department of Pharmacokinetics
Institute of Experimental Pharmacology
Slovak Academy of Sciences
84104 Bratislava
Slovakia
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