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[Not quite PK but maybe close enough - Offers to dclaghorn.-a-.ilexonc.com
please but any PK/Biopharm comments could come to the list (as well) - db]
My company is developing a highly potent compound (new chemical entity)
for oral administration and need to find someone (manufacturer) who can
help us with multiple runs of differing doses of a low volume of
capsules for a clinical trial. Because of the potency of this compound,
cleaning validations will probably be very difficult due to the
requirement to measure residuals at the femtogram level (I said it was
potent). We currently do not have any human tox data on this compound,
but are thinking after we get those data from phase I testing, we should
be able to move the validation to the pg level.
We are using a 2-5 mcg dose, and it is based in miglyol (200
microliters). Our initial thought is to use a softgel capsule, and we
have contacted RP Scherer in St. Petersburg, FL. The main problem that
we are having with them is the level of detection for the cleaning
validation. Do you think that a softgel a viable option, or could we
use some type of hard gelatin capsule for a miglyol based dosage form?
What about packaging in an oral syringe? We have toyed with the idea of
purchasing dedicated equipment, but that is, obviously, quite expensive.
Additionally, we are considering the hand filling of gel caps (a couple
hundred at most, for the trials) with a syringe. If we were to do this,
what would be the best way to seal these?
Thanks to anyone for their help,
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Your question is aninteresting one and a challenging one! have you
thought about formulating your drug as a transdermal? High potency drugs
are potential transdermal candidates but one would need to know more
about the phys/chem properties to offer an informed opinion, (which I
guess are condidential at present). I imagine that the therapeutic
window for such a potent drug is very narrow and an oral dosage form may
give a 'bolus' dose initially which might bring blood levels into the
toxic area. A dosage form which irons out the peaks and troughs of oral
or i.v. doses is what is required. Some transdermal devices can provide
the tight degree of controlled release for these type of drugs.
However, we are back to the catch 22, the toxicity and safety of this
drug must be known before any large scale work can be undertaken.
For assay, have you used ELISA tests for detection at low levels?
Such tests can detect down to pg or even femtogram levels.
Is this drug from a natural source, say from the oak tree ?
I hope that some of this helps.
Stowic Resources Ltd.
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