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We are planning to conduct BE studies for our formulation against a RLD
which also is an orally disintegrating tablet. Is it necessary to
perform fed studies also, as wehad performedfor the conventional
product. If yes, theviews behind the conduct of food effect study for
orally disintegrating productsshall be of great help to us.
Regards,
Naveen Sharma.
Sr Scientist, APL- Research Center
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Dear Navin,
In your case it depends on the kind of drug your Rapidly disintegrating
Tablet might contain.For all practical purposes this types of dosage
forms should be classified under Immediate Release peroral forms like
IR tablets/Suspensions.
In fact scientifically speaking with reference to dasage form per se, a
rapidly disintegrating Tablet will be least affected by the
physiological behaviour of the stomach (whether in food and Fasting
condition) so the decision should be based on
1) BCS Class/PK of the drug incorporated in the rapidly disintegrating
dosage form.
2) Whether the drug is a Highly variable drug/ having nonlinear
kinetics/highly toxic/having narrow therapeutic index.In few such cases
a fed stage BE would be generally desirable.
3) Does the label of the RLD specify any recommendations like dosage
forms to be taken with food only or with empty stomach.In earlier case
a fed state BE would be desirable.
I hope this will suffice the purpose,
Awaiting your comments,
Kind regards,
Pradeep Bhadauria
RANBAXY RESEARCH LABORATORIES.
INDIA.
Dear allBack to the Top
I'm not sure that I agree with Pradeep when he writes that a fed study
is desirable when..... "the drug is a Highly variable drug/ having
nonlinear kinetics/highly toxic/having narrow therapeutic index. In few
such cases a fed stage BE would be generally desirable." Isn\0xEDt the main
reason that a marked effect of food will render absorption so variable
that it is not safe or practicable to market the compound, unless it
has some other unique property? That means every NCE will need a fed vs
fasting study and most of the clients we deal with do it very early on
in Phase 1. Considering that virtually all compounds in modern
practice have already passed this test I think it unlikely that slight
changes of formulation or a move to generics will make much difference.
Accordingly, I doubt that it is justified to do the study routinely.
However, I would like to use the power of a forum like this to pool
experiences and would ask if anyone knows of formulation changes
having an effect on bio-availability with food (other than the obvious
coated and slow release forms). Perhaps we could identify the
circumstances that do make a difference.
I agree with Pradeep that changes in gastric emptying affect the Pk
profile less after rapidly disintegrating formulations than those that
take many minutes if you take an absolute view, but I would point out
that the effect can be considerable if you take a percentage view.
For an example see Rainbird AL et al 1987 J Pharmaceutical medicine
2, 35-42, who reported a 27% difference in liquid emptying at 10
minutes after ingestion between a semi-supine posture and sitting
upright, and a 17% difference between semi-supine and lying on the
right side. Such differences could affect Cmax considerably and would
certainly raise questions in the analysis of a BE study.
Kind regards
Andrew Sutton
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Dear Mr Sutton
I have recently read a paper showing that the formulation is
determinant of amiodarone bioavailability (Bioavailability of
Amiodarone Tablets Administered with and without Food in Healthy
Subjects; X. Meng, P. Mojaverian, M. Doed\0xC8e, E. Lin, I. Weinryb, S.T.
Chiang and P.R. Kowey; Am J Cardiol, 2001;87:432-435).
Amiodarone has complex solubility properties, including its capacity to
form micelles, which are susceptible to changes in formulation factors.
Maybe it is a good starting point for the discussion...
Regards,
Paula Macedo Cerqueira, PhD
Pharmacist
Bioequivalence Unity
Nacional Health Surveillance Agency - ANVISA
Brazil
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Naveen,
For a bioequivalence study, an orally disintegrating tablet should be
classifed in to same class as that of immediate release tablet. Unless
the RLD clearly mentions the absence of food effect on both rate and
extent of drug absorption, or specifies that the dosage form to be
taken only on empty stomach for regulatory purpose, bioequivalence
study under fed condition is necessary.
Regards,
Sunil Vandse
Able labs
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Dear Naveen,
Let me know whether your product is conventional or any controlled
release formulation.
As per new guidelines of USFDA, in case of an immediate release
formulation, the fed study has to be done. Where as in case of
conventional product, it may not be required unless the RLD comments on
the effect of food.
Regards,
KANTHI KIRAN,
Glenmark Pharmaceuticals LTD.
INDIA.
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Dear Naveen,
Please note the typing mistake I have written in my earlier reply. " in
case of an immediate release formulation, the fed study has to be done."
Here I wanted to write you the non immediate release formulation. I
apologies for the same to the group.
Regards,
KANTHI KIRAN
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