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I would appreciate some information about the effect of
different salt forms of the same drug in their pharmacological profile
(solubility, absorption, etc). Is there any reference about this in the
literature?
Is it any preferred form by FDA (HCl, Acetate, TFA, etc)?
Than you so much for your help.
Jose M Valdivielso PhD
Staff Scientist
Adaptive Therapeutics
5820 Nancy Ridge Suite 200
92121 San Diego Ca
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Jose,
I am concerned that there is no real law concerning salts in terms of
solubility, absorption, etc...
A salt enhances the drug solubility so that it can be dissolved in a
much
easier way. But if you are dealing with pharmacological effects you
should
not find any difference between parent drug and salt.
Dissolution will vary and absorption as well if it is dissolution
dependent.
However there is no FDA guidance for salt selection. FDA even does not
need
any safety study if your salt refers to an existing drug and if its
pharmacokinetics and pharmacodynamics are similar to the parent drug or
to
other salts that are already documented. See more info here:
http://www.fda.gov/cder/guidance/4461fnl.htm#P234_21126
Regards,
Frederic DOC
PFIZER Global R&D
Fresnes Laboratories
FRANCE
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The following message was posted to: PharmPK
Dear Dr.Jose,
The physical properties of the different salt forms may differ and this
in turn may affect the pharmacokietics of the moiety in some cases.(
solubility of sildenafil citrate and maleate).
However, FDA does not ask for any specific preference in selecting
salts for NDA submission of new drug.Your decision regarding which
particular salt to be considered in lead stage of drug development
should be based on step-by-step and preferential evaluation of the
parmeters such as safety, efficacy, desired pharmacokinetics and drug
metabolism effects, physicochemical properties like stability on
storage ,solubility and LogP etc. and also ease of synthesis. Although
due to toxicty/solubilty/absorption etc.reasons sometimes we have to
select diffrent salts form for diffrent formulations via different
routes of administration. ( Injection Vs.Tablets)
It is advisable to have a comparative evaluation in generic way for
better decision making, there should be a preliminary model and
selection criteria in drug discovery to identify the drug salt as it
may not be feasible to screen all salt forms for all the above
mentioned key features.And the decision should be taken preferably in
preclinical stage or sometimes early clinical stages to avoid
unnecessary regulatory burden.
Kind regards,
Pradeep S. Bhadauria
Ranbaxy Research Laboratories.
INDIA.
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The following message was posted to: PharmPK
Frederic:
What is your concern exactly about the absence of FDA guidance on salt
selection? As you wrote, it is most unlikely that the salt makes any
real
difference in terms of adverse effects. Differences in absorption do
not
count because it is easy to adjust the dose or formulation release
characteristics. That being so I find it hard to understand why anyone
would
want FDA guidance or even a law on the topic
Andrew Sutton
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The following message was posted to: PharmPK
Andrew,
I have no concern about this. In fact I was just replying to the
following
message:
I would appreciate some information about the effect of
different salt forms of the same drug in their pharmacological profile
(solubility, absorption, etc). Is there any reference about this in the
literature?
Is it any preferred form by FDA (HCl, Acetate, TFA, etc)?
Than you so much for your help.
Jose M Valdivielso PhD
Staff Scientist
Adaptive Therapeutics
5820 Nancy Ridge Suite 200
92121 San Diego Ca
Regards,
Frederic
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