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Dear all,
I have to administer some plant extracts (of hexane, chloroform, ethyl
acetate and methanol) to mice orally. These extracts are soluble up to
some extent in DMF(Dimethylformamide), and to a lesser extent in pure
DMSO(Though a clear solution is not obtained in any of the above case).
These extracts are insoluble in almost all the other solvents which I
tried. They don=92t dissolve even in 5% CMC with a little amount of
tween 20. All the extract are in paste form and very sticky. Can any
oil be used to dissolve them. Can anyone guide me whether extracts
dissolved in DMF/DMSO/80% ethanol (In suspension form as I am getting)
can be given to mice and up to what percent these are permissible for
giving to mice/rat. Is there any reference for any other solvent which
can be given orally to mice and unto what percent.
=0AAny
answer to these questions would be of great help in my work. And I
would be very obliged.
Thanks in advance
Poonam Shokeen
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Dear Poonam,
You will be very lucky if you can solubilize a plant extract without a
significant proportion of organic solvant, as you used hexane,
chloroform etc. for extraction there is probably only few hydrophilic
molecules. You should then first look to obtain a suspension of
adequate particle size and homogeneity. I can suggest a solution of
30% hydroxypropyl-beta-cyclo dextrin which often yields perfectly
acceptable suspension, alternatively 50% propylene glycol or 25% PEG400
can be used. Use successive sonication vortexing to ensure
homogenization and avoid any heating. If you end up with homogenous,
fine particle suspension (it is preferable to measure the particle if
possible, using heatocytometer chamber) this is perfectly acceptable
for oral administration to rodents via a standard gavage needle.
Good luck,
Jean-Pierre Moreau
Pre-Clinical and Clinical Studies
Biopharmacopae Design International
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Hello Poonam,
You can use DMF/DMSO/80% ethanol in your mice/rat oral dosing
formulation
and if you keep aqueous phase around 60% and none of individual
solublizing
agent more than 20 % in your final formulation it is generally
considered
safe (though these are not magic figures).
It is a common practice to orally dose mice/rat with suspension dosage
form,
in preliminary preclinical studies. What is important here is, you
should be
able to formulate a homogenous suspension for dosing uniformity.
Triturating
your drug/extract with a small amount of Tween 80 usually provides
adequate
wetting which when diluted with 5 % aqueous Na CMC gives a homogeneous
suspension.
In case in your future studies you are interested in IV dosing, where
you
essentially need a solution, you may also try beta-cyclodextrin as
solublizing agent. Since you asked for an oil as solublizing agent
Cremophore EL (poly hydroxylated castor oil) can also be tried at
concentration less than 20 %.
Good luck for your studies.
Vijay V Upreti
Gradaute Student
Pharmacokinetics-Biopharmaceutics Laboratory
Department of Pharmaceutical Sciences
University of Maryland
20 Penn St., Baltimore, MD 21201
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Dear Poonam,
Since your compound is a paste, the possibility of ending up with the
compound sticking to the container is very high when you try to
formulate.
The best possible option is to dissolve it in the DMSO/DMF or a mixture
of
DMSO and DMF (you can go upto 20% v/v since you intend to administer by
oral
route). Once you dissolve the compound, add the solution to a 20 - 40%
hydroxy propyl beta cyclo dextrin solution to form a dispersion or an
inclusion complex. This might be a reasonably good approach to handle
such
tacky pastes, All the Best, Jagannath
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Dear Poonam,
That sounds like a challenge in formulation, let alone doing PK.
Anyway, cmc is probably Carboxy-methyl-cellulose? Have you tried mixed
micelles. This may give you an idea that solubility in lipid formulation
(micelles) might work. The worry is then you can end up with a massive
food effect but there you go. I think there is propriety stuff out there
that helps formulating your compound; maybe look at
http://www.phares.biz/ it is
just an example firm.
Regards
Hans Smit
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Hi, This is Lingzhi, a PhD candidate from National University of
Singapore. According to my experinece, you might try using Cremophor EL
as the solvent. Good luck! Hope it is helpful.
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Dear Poonam,
You can try out following solvents form the preliminary information
that you have provided it looks like your compound is lipophilic you
can try out the NMP ( N-methyl Pyrolidone) ,a combination of SLS and
tween as a surfactant ,if you need any information abt NMP do let me
know
Regards
ATUL
Novel Drug Delivery Systems
Glenmark Research Center
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)