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The following message was posted to: PharmPK
I have a lipohilic, poorly soluble compound. I need an oral
formulation ultimately but until I confirm oral bioavailability I
will be injecting the compound IP.
The initial POC study solubilized the compound in 10%DMSO/90%PEG400,
however, the compound precipitated at the injection site.
Any formulation suggestions for preventing compound precipitation
after IP injection to conduct POC anti-cancer efficacy studies?
Steve
[Can you give a larger volume? - db]
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The following message was posted to: PharmPK
Dear Steve,
Drug precipitation can be substantially sustained or
prevented by dilution of DMSO stock solution with
aqueous/buffered cyclodextrin solutions with different
concentrations.
If hydroxypropy-Beta-cyclodextrin not effective
enough, try the methylated derivatives such as DIMEB or
RAMEB, which prooved to be the most powerful solubilizers.
The sequence of the dilution is also important, adding
cyclodextin solution to DMSO stock solution is advised.
Some addition to the concern of cyclodextrin complexed
drug availability:
Because of the significantly higher dissolved drug
concentration, the dynamic nature of complex
association-dissociation and the moderate value of binding
constant of the complex in the most case, free drug
fraction will be always present for absorption.
Complexed drug release is fully discussed in the review
paper of Valentino J. Stella et al, Mechanism of drug
release from cyclodextrin complexes, published in: Advanced
Drug Delivery Reviews, 36 (1999), p3-16.
For oral bioavailability testing, cyclodextrin based
formulation of such kind of drugs is also advised. Based on
my experience, surprising results can be predicted in
favour of the cyclodextrin formulation compared to the control.
I hope this will help to solve the problems.
Best regards: Maria Vikmon
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The following message was posted to: PharmPK Maria,
Molecules closely related to my compound are soluble in Tween 80 (~20
mg/ml). The addition of cyclodextrins (3% or 6%) to the surfactant
slightly lowers this solubility.
There have been solubility studies using microemulsion systems like -
isopropyl myristate (36.3%)/isobutanol (4.5%)/Tween 40-Span 20 3:1
(40.9%)/water (18.3%) that were effective, but addition of various
cyclodextrins lowered the solubility of the microemulsions.
Anyone know if mice would tolerate ip injections of the microemulsion
described above?
Steve
--
Stephen Gately, Ph.D.
RND Pharmaceuticals, Inc.
853 N. Quentin Road Suite 195
Palatine, Illinois 60067
(847) 420-9094
(847) 346-8555 (Cell)
(847) 776-8506 (Fax)
http://WWW.RNDPHARM.COM
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The following message was posted to: PharmPK
Dear Steve,
Surfactants are good complex forming agents with
cyclodextrins. Tween 80 and isopropyl myrisate are
competitive guests for inclusion, and this is the reason
of solubility decrease.
DMSO and ethanol solubilized stock solutions are offered
for dilution with cyclodextrin solutions.
Best regards,
Maria Vikmon
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)