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Dear All,
Is any one has any idea about chewable tablet. iIf we want to study
BE of chewable tablet, when administer the drug do the subject need
to chew the tablet before swallow?
Wichittra
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hi
yes the subjects need to chew the tablets before swallow with water.
ramu
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The following message was posted to: PharmPK
Does the manufacturer require chewing? If chewed and swallowed the
release based on surface area will be much larger than an intact tablet.
If the area is greater, the release and absorbance should also be
greater!
Ed O'Connor, PhD
Technical Director, Immunoanalytical
Tandem Laboratories
115 Silvia Street
West Trenton, New Jersey
609-228-0243
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The following message was posted to: PharmPK
If I may add a comment to Ed O'Conner's point, not only will
absorption be
faster the more the tablet is chewed but a greater proportion will be
presented to the brain due to the carotid blood supply of the region
around
the mouth compared with the gut. If it passes the blood brain barrier
more
will be absorbed into the brain.
Andrew Sutton
Guildford Clinical Pharmacology Ltd.
The Technology Centre, Occam Road
Guildford, Surrey, UK. GU2 7YG
URL: www.gcpl.co.uk
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Dear All,
Thank for the suggestion on Chewable Tablet BE. I want to clearify
about my question. What I ask was if we want to study the
bioequivalence of chewable tablet (such as Montelukast) between
Reference and Test formulation, do we need to ask the subject to
chew the tablet before swallow. The labelling of the product state
that it need to be chew before swallow. I agree with the idea that if
we chew the tablet before swallow the aborption rate will be more
rapid. But when conducting the Bioequivalence study both
formulation , Reference and Test are under the same condition (chew
before swallow) so it may be reflect the real situation when using in
patients. Please let me know if this study dsign is not suitable
Wichittra
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The following message was posted to: PharmPK
Dear Wichittra,
I believe you should follow the package insert for both formulations.
Some amount of absorption via the oral cavity would be likely with the
chewed tablet. Depending on the amount and the length of time the
drug is in
solution in the mouth before swallowing, absorption can take place
through
lingual, sublingual, and buccal routes. Swallowing the chewed tablet
quickly
could minimize oral cavity absorption, which could result in lower
bioavailability if there is significant first pass extraction via
absorption
in the gastrointestinal tract. This is because absorption via the oral
cavity bypasses first pass extraction in gut and liver. So for a drug
with
high first pass extraction, even a relatively small amount of drug
absorbed
via the oral cavity could result in enough change in bioavailability to
affect Cmax and AUC to a sufficient degree to affect demonstrating
bioequivalence.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (AMEX: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
U.S.A.
http://www.simulations-plus.com
Phone: (661) 723-7723
FAX: (661) 723-5524
E-mail: walt.-a-.simulations-plus.com
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Hi Wichittra
You are absolutely right the absorbtion will be rapid as oral
absorbtion will eliminate the first pass metabolism,
in your situation if you are conductng a BE then you will have to
make sure the subjects chew the tablet (both test and reference)
before swallowing (as that is claimed by label). only thing you will
have to make sure they chew tablets slowly
or else you will observe variability.
Hope that helps...
Best Regards
Bharat
Wockhardt
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Dear Walt,
In case of drug administration for chewable tablets,how can we make
ensure that the volunteer is chewing the tablet and not crushing it
or swallowing it.Also chances are that, he can chew a part of the
tablet and swallow the remaining.in those situations wont there be
difference in bioavailability ?
please clarify
Thanks
Mohammed Muhiyideen
Quest life sciences pvt ltd
Chennai
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The following message was posted to: PharmPK
Mohammed,
This would be a complication in demonstrating bioequivalence for any
chewable dosage form of a drug with high first pass extraction. If
the drug
does not undergo high first pass extraction, you might have negligible
effect from oral cavity absorption.
Keep in mind that the innovator only has to show safety and efficacy,
so if
these are demonstrated within the variabilities of a population,
there is no
problem. But a generic company has to demonstrate bioequivalence, so the
problem could be a bit tougher if first pass extraction is high.
If it was my study, I would try to establish a protocol for ensuring
that
the tablets were chewed and swallowed as uniformly as possible by all
subjects. It seems to me that the best way to ensure that would be to
have
all subjects chew the tablets until they are "completely" ground up,
then
have them swallow.
I hope this helps. Please note that my comments are theoretically
based - I
have no direct experience in this area. Perhaps someone with some actual
practical experience in this area can provide more/better advice.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (AMEX: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
U.S.A.
http://www.simulations-plus.com
Phone: (661) 723-7723
FAX: (661) 723-5524
E-mail: walt.aaa.simulations-plus.com
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The following message was posted to: PharmPK
Dear Wichittra,
Yes, both test and reference tablets should be chewed. Make sure the
subjects chew the tablets thoroughly. Go ahead with the study.
Regards,
Dr. Gagandeep Singh
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The following message was posted to: PharmPK
dear,
specify for chew. tablet just make sure about the protocol for dosing
chewing the tablet completly for some specific period i.e 3 min or 2
min. so you can easily do mouth check for the dosing compliance after
swallow the tablet.
there is no big differance for that but your plan like this way give
you assurance for all subject for test and ref. and as well as
compliance also.
best regards,
paresh
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The following message was posted to: PharmPK
Dear Wichittra,
In the past, I have conducted a couple of studies on chewable
tablets. One
of them involved comparison of the chewable tablet with a conventional
tablet. As Walt stated earlier, "If the drug does not undergo high first
pass extraction, you might have negligible effect from oral cavity
absorption". For a drug like montelukast, I guess this should not be a
problem.
For the dosing of chewable tablets, we told the subjects to chew the
tablets
for 2 minutes. Post that, a quick oral cavity observation was
conducted to
ensure complete disintegration of tablet. Then the subjects were
instructed
to swallow the disintegrated mass. Moreover, it will be helpful if your
study personnel can give a demo of the process using placebo tablets to
ensure uniformity in process.
Best wishes,
Rhishi
Rhishikesh Mandke
Presidential Fellow
Department of Pharmaceutical Sciences
North Dakota State University
Fargo ND 58103
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