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The following message was posted to: PharmPK
Dear Frederic,
Would you please recommend a good text book/reference
material for preparing formulations for various routes
of administration (mainly iv and oral)?
Thanks
Rostam
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Dear Rostam,
as far as I know there is no reference book about preclinical
formulation strategies.
Maybe I should become the author of the first one !!!
Seriously the development of a RELEVANT formulation strategy should be
conducted by experienced formulation scientists working closely with
pharmacology , tox and PK scientists.
This is a complex process that should lead to recommended formulations
for each "animal species - study design" couple.
When I was working at PFIZER we developed such a strategy with
dedicated formulations for various couples : rat/PK, dog/PK, monkey/PK,
Mouse/POC (Proof Of Concept), Rat/POC, rabbit/TOX, guinea pig/TOX, etc.
I suppose that other discovery organisations have the same kind of
preclinical formulation strategy to ensure the relevance of preclinical
data.
Please do not hesitate to contact me for further information.
Best regards,
Frederic
Frederic Doc
Acriter - drug discovery consulting
www.acriter-consulting.com
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Dear Rostam,
I have found the following paper very helpful in terms of outlining a
strategy for formulating compounds with low or unknown solubility:
Lee, Zocharski, Samas: "An intravenous formulation decision tree for
discovery compound formulation development", International Journal of
Pharmaceutics 253, Pp. 111-119, 2003.
Very best regards,
Chris Pasetka
Senior Research Associate
BC Research Building
3650 Wesbrook Mall
Vancouver, BC, Canada
V6S 2L2
Phone: (604) 221-9666 ext. 242
Fax: (604) 221-9688
e-mail: cpasetka.-at-.migenix.com
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Dear Federic
I found this book more useful in preformulation strategy :
J. I. Wells, Pharmaceutical Preformulation: The physicochemical
properties
of drug substances, Ellis Horwood series, 1988
Sincerely,
Hamed Hamishehkar
Department of pharmaceutics
School of pharmacy and pharmaceutical sciences
Isfahan-Iran
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Dear Chris,
this paper was written by some of my former colleagues working at
Pfizer, Ann Arbor MI.
Sharing experience with them about this, my personal point of view was
that this decision tree was not well-adapted to each "animal
species-study design" couple mentioned in my previous message.
But this decision tree is one part of the "full discovery formulation
strategy" each research organisation should have.
Cheers,
Frederic
Frederic Doc
Acriter - drug discovery consulting
7 rue Montespan
91024 Evry cedex, FRANCE
URL : http://www.acriter-consulting.com
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Dear Hamed,
many thanks for the reference.
But let me point out the fact that at the preclinical stage formulation
scientists should have two different activities :
1- they should focus on identifying the "preformulation profile" of the
future drug candidates for development. This work should lead to
recommendations/guidance to choose the way the future commercial dosage
form will be developed.
2- they should also support preclinical studies by providing relevant
formulations for animal dosing.
The book you are refering to is that kind of book that was written to
support the preformulation work (point 1).
What Rostam was originally looking for is a reference guide for the
strategy to be developed in point 2.
Rostam,
i cannot provide you with the complete strategy I have in mind because
it is too large but if you give me more details about what you are
waiting for I should be able to provide some guidelines or
recommendations.
Do not hesitate to contact me at fdoc.aaa.acriter-consulting.com
(professional e-mail)
Hope this helps,
Frederic
Frederic Doc
Acriter - drug discovery consulting
7 rue Montespan
91024 Evry cedex FRANCE
www.acriter-consulting.com
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The following message was posted to: PharmPK
Thanks Frederic for your interest, expert knowledge
and help. At this point, I have a general concern
regarding pre-formulation strategy of poorly soluble
compounds. Some formulation chemists prefer to use
formulations containing high % of organic solvent
(e.g., ~20% DMA or DMSO, ~20% Tweeen 80 or PEG, the
rest saline or Dextrose solution = aggressive
formulations) compared to less aggressive formulations
(e.g., 1% CMC, 0.1% Tween 80 and the rest water). They
like to argue that for ranking purposes of many
compounds the aggressive formulations will do the job
but the down side is that this type of formulations
are often non-realistic and you need to move to less
aggressive formulation for Tox studies or clinical
use. Any comment or input is appreciated. BTW Chris,
the paper that you mentioned was quite useful.
Rostam
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Dear Rostam,
as you certainly anticipate, I do not fully agree with the formulation
chemists you refer to.
"Agressive" formulations may not be used in PK studies because as you
said, and I fully agree with you, they are non-realistic.
But the use of less agressive formulations may not be considered only
for tox and clinical studies. For instance preclinical PK studies also
need to be performed with relevant formulations.
How do you argue that PK results are relevant if you use such agressive
formulations leading to precipitation events for some of them and to
some absorption enhancement for others ?
I am quite surprised about formulation chemists' attitude as they
should be the first ones to point out the potential impact of drug
dosage forms in preclinical studies.
Best regards,
Frederic DOC
ACRITER - Drug discovery consulting
please visit our website at : http://www.acriter-consulting.com
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