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In the USP in the section on Drug Release Testing on page 1793, there is a
statement about media replacement which reads (in summary) that you do not
have to replace sampled media if it can be shown that it doesn't affect
drug release. How, other than showing that sink conditions aren't
compromised, does one show that not replacing the sampled media doesn't
affect drug release?
Claud G. Cameron
cameronc.at.ix.netcom.com
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[Two replies - db]
From:
Date: Fri, 21 Aug 1998 16:14:31 EDT
To: PharmPC.at.pharm.cpb.ouhsc.edu
Mime-Version: 1.0
Subject: Re: Drug Release Testing
Demonstrate that there is no statistical difference between drug release with
and without media replacement. Establish acceptance criteria in the protocol.
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From:
Date: Sat, 22 Aug 1998 06:53:37 EDT
To: PharmPC.at.pharm.cpb.ouhsc.edu
Mime-Version: 1.0
Subject: Re: Drug Release Testing
The only technique I know of is carrying-out the dissolution with a single
batch of the highest strength dose units (capsules/tablets) enough times to
provide sufficient confidence that not replacing the medium and adjusting your
calculations will not change the results. You should carryout the dissolution
run to what I guess is still called a "t-infinity" point. That is, if your
conditions are 100 rpm for 30 min, then adjust the rotation rate to maximum
(250 rpm?) for another 30 - 60 min and analyze a sample. If the concentration
has not changed significantly (within analytical variation and with no
degradation) from your 30-min pull, then media removal is not affecting your
release rate. Maintaining sink conditions is good indication of adequate
solubility, but stating this theoretically is not sufficient (because of other
potential interactions such as active-excipient binding at certain
concentrations and not at others). You should demonstrate that that media
replacement is not necessary experimentally.
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You can carry out the test in paralel. On the one hand you don't replace
the sampled media. On the otrher hand, you do replace the sampled media.
Then you simply have to demonstrate that both sets of results dont differ
each other statistically.
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David Bourne (david@boomer.org)