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Dear All,
We are working on an NCE which is insoluble(
40micrograms/ml.This is intended to be delivered as
dry powder inhalation for studies in rat.There are
two approaches being investigated
1.A dry powder blend with respitose(inhalation grade
lactose).
2.Amorphous captisol-NCE spray dried powder.
The captisol spray dried powder would dissolve on
administration(solubility in captisol 5mg/ml).
could anyone guide as to which would be a better
formulation for drypowder delivery?.Are there any
drawbacks of captisol for inhalation delivery?
best regards,
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It largely depends on intended dose to be delivered via inhalation
route. Dose upto 1-2 mg should easily be delivered by conventional dry
powder delivery through a powder blend of drug ininhalation grade
lactose. If dose is more than 5mg you may look for neat API delivery if
the surface properties, flow and aerodynamic particle size distribution
profile through DPI device are satisfactory.If not then cetainly you
may adopt a particle engineering approach (eg. spray drying) for
effective delivery of NCE or NCE-Cyclodextrin complex.
Is this NCE intended for local lung delivery or systemic delivery via
lung?.
Currently cyclodextrins are not approved excipients by
inhalation route so the latter approach will certainly impose exhautive
toxicological screening of this new excipient.
I hope this addresses
your issue,
Kind regards,
Pradeep Bhadauria
Lead Scientist
Plumonary and Nasal Delivery
Cardinal Health Inc.
RTP,NC,USA.
919-465-8161.
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Dear ramdas,
Nice to hear from you after a long time.
As far as captisol is concerned, it has been used for IV and IM adm
and seems pretty safe.As pradeep had mentioned b-CD is unsuitable for
systemic delivery as it causes necrosis of proximal kidney tubules.
But two drug formulation containing captisol, which is another form
of CD ( sulfobutylether b-cyclodextrin, SBE-7-b-CD) are in phase III
clin. trials in US and have an established DMF with FDA.
though CDs should be used with caution as they can accelarate drug
degradation and sequester preservatives rendering them ineffective.
it seems you are looking for systemic delivery rather than local
action.again care must be taken to have a proper MMAD of particles to
have deep lung delivery and deagglomeration of lactose particles when
using a DPI.
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Dear Ramdas & Pavan,
Just a clarificantion on what I mentioned and
what has been interpreted seems to have no co-relation.
All I wanted
you to convey that Captosol is not an approved excipient via inhalation
route. It is well established fact that cyclodextrins are approved by
injectable route but it doesn't necessarily qualify the exciepient for
critical routes like inhalation. Everybody who are into inhalation
delivery are aware with the fact that tolerability of excipient via
inhalation route can't be correlated with its historical good
tolerability via other routes including IV. Most of the regulatory
agencies doesn't consider this arguement as a stand alone tool when we
try and submit formulation with any new excipients which are not
approved by inhalation.Which is why we have only 15 to 20 excipients
approved by Inhalation route as opposed to around 75-100 excipients
approved by injectable route.If agency will start considering all
excipients approved by injectable route deemed approved by inhalation
also ( by your definition),jobs of inhalation s
cientists will be much
easier but this is not the case.
My opinion was not towards barring
you from using Captisol but to let you know the current regulatory
status of captisol with reference to Inhalation
delivery.
Lastly,irrespective of its local or systemic intended
use,in an attempt to deliver drugs via pulmonary route even for systemic
action ( deep lung delivery) you are bound to expose considerable part
of your formulation to local areas like oropharynx,proximal lung,central
lung before it reaches deep lung as none of the DPI delivery systems are
efficient enough for more than 50% systemic delivery, I guess
so.
Good luck,
Regards,
Pradeep Bhadauria
Pulmonary &
Nasal
Cardinal Health Inc.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)