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The following message was posted to: PharmPK
Dear all,
we are doing Ramipril study using apple sauce. can any body tell me
what is
the use of apple sauce for dosing. Is there any special for using apple
sause for dosing.
any information is appreciable
srinivasa reddy.
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Hi Srinivasa,
The drug label for ALTACE indicates that, "In a trial in which
subjects received ALTACE capsules or the contents of identical
capsules dissolved in water, dissolved in apple juice, or suspended
in apple sauce, serum ramiprilat levels were essentially unrelated to
the use or nonuse of the concomitant liquid or food."
I believe that, for ANDA submission, bioequivalence should be
demonstrated on RLD by using both the treatments sprinkled on one of
the soft food mentioned in the labeling eg. apple juice or sauce, in
addition to the regular fasting and fed BE studies.
Please refer: http://www.fda.gov/cder/guidance/5194fnl.pdf
Best wishes,
Niraj Shethji
Biovail Contract Research
Tel : (416) 752-3636 Ext. 394
Fax : (416) 752-7610
URL : www.biovail-cro.com
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Hi Srinivasa
I myself don't know why applesauce is preferentially used. My guess
would be the commercial ease of availability in the United States. In
cases of pediatric or geriatric populations there have been
incidences when the subjects are not able to swallow the entire
intact capsule, hence there has been a practice of opening the
contents of the capsule on to a tablespoon of applesauce and
swallowed without chewing. The next issue that could arise on
exposing the beaded contents onto a tablespoon of applesauce is
chemical instability of the API that would reflect directly to the
potency of the product. Hence the agency likes to know whether the
generic product is bioequivalent to the RLD when exposed in this
manner. In my perspective the time during which the contents are
exposed to the applesauce is very unlikely to cause product
instability for most drugs but there may be cases like Omeprazole
that is very sensitive to light and is acid labile too. The fasting
condition sprinkle BE study is rather a conservative approach and
definitely an additional expense.
Hope this helps
Manish Issar, Ph.D
Sandoz Inc.
4700 Sandoz Drive
Wilson, NC-27893
USA
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Hi Srinivasa,
I guess its just an alternative method of drug administration. In
children, geriatrics, and people with dysphagia, there is poor
compliance due to problems in swallowing a solid oral dosage form.
Hence to facilitate swallowing, the granular contents are mixed with
applesauce prior to oral administration. Inorder to evaluate whether
this affects the pharmacokinetic profile of the drug, such studies
are conducted.
Hope this helps.
Regards
Ganesh
--
M.M. Ganesh
PhD Student
College of Pharmacy
University of Cincinnati, Ohio, USA
My Web Page: www.geocities.com/ganaish/gans
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The following message was posted to: PharmPK
Dear Srinivasa reddy,
If you look instructions for administering the dose of ramipril, it
can be
given with plain water, apple juice or can also be given with apple
sauce.
Administration of ramipril in apple sauce is particularly useful for
patients with swallowing difficulty.
For example, all patients with stroke are screened for dysphagia
before any
medication is given by oral route. A simple bedside screening evaluation
involves asking the patient to sip water from a cup. If the patient
can sip
and swallow without difficulty, the patient is asked to take
medication with
a large gulp of water and swallow. But if patient is not able to gulp
the
medication with the water (due to coughing or may be due to aspiration),
medications can be given in applesauce or jam, wherein you increase the
viscosity of the vehicle. This helps in patient compliance.
Ramipril is prescribed for patients with cardiac failure and is given in
doses of 2.5, 5 or 10 mg (very low dose). It is important that, patient
takes the complete medication, and should not loose any drug due to
coughing
or aspiration. This also can be facilitated by using viscous vehicle
such as
apple sauce. (But precaution should be taken that it is not too hot)
It is well documented through various clinical trials that,
administration
of ramipril in apple sauce did not alter its pharmacokinetics in humans.
Secondly, it is logical think about the stability of ramipril in apple
sauce. In a study published on stability of ramipril in water, apple
juice
and apple sauce, it was found to be well stable in apple juice (to be
precise stable up to 24 hours at 23 degrees and stable up to 48 hours
at 3
degrees). (Allen LV Jr, Stiles ML, Prince SJ, McLaury HJ, Sylvestri MF.,
Stability of ramipril in water, apple juice, and applesauce, Am J Health
Syst Pharm. 1995 Nov 1;52(21):2433-6).
These may be the reasons for such a vehicle in your bioequivalence
protocol.
Hope this helps.
Prashant
BITS, Pilani
--
Kole Prashant
Pharmacy Group
Birla Institute of Technology and Science, Pilani.
Rajasthan, 333031
India
Phone: 01596-245074- ext - 458 [0ff]
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Dear Srinivas,
You can refer the USFDA guidance "Food -Effect Bioavailability and
Fed Bioequivalence Studies". Look under OTHER CONSIDERATIONS
"Sprinkles".
Nisha K R
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