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Dear all,
I have a few questions;
1) Does anybody know an internet site includes free pharmacokinetics
books or booklets?
2) Has anybody seen any IVIVC data or any IVIVC study about statins
(esp. Atorvastatin) ,
cox-2 inhibitors (esp. meloxicam) and proton pump inh (esp.
pantoprazol )?
3) The last question is for IR and MR drug products ; in R&D, QC
studies or post approval changes which requires comparison of in vitro
dissolution profiles;which method (ANOVA-based or other statictical
methods, model dependent or model independent methods) do you prefer to
practise?and why ? It's known that similarity factor is
recommended in FDA guidelines. But it has disadvantages and less
discriminative than the other methods ( ANOVA-based methods ) ; Do the
disadvantages of the similarity factor make you practise different /
alternative methods ?
I will really be appreciated for the answers ; thank you,
Erdem Güven
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The following message was posted to: PharmPK
Erdem Güven
I do agree with you that more often than not Similarity factor value
needs to be supplemented by the other more discriminatory alternatives
methods like ANOVA and dissolution rate comparision models that can
provide the stastistically significant outcome of the test.The 10 %
difference in the % drug released permitted by F2 comparison ( F2 =
50)actually gives different levels of the % variation at different
levels (time points)of the dissolution cycle ( Based on % drug
dissolved: Initial, Middle and Terminal) say for example if we compare
the following data:
RLD Test
20% 10%
50% 40%
100 90%
The calculated f2 would be 50 but if one will observe % deviation from
the RLD : on initial point it is 50%, Middle it is 20% and end it is
10% and it does creat a need for a better and discriminatory method or
atleast needs the acceptance criteria to be made narrow. But
acceptability of any New approach by FDA is still a question mark.
On IVIVC front, Atorvastatin is so poorly bioavailable ( abs
bioavailability of 14%)and it is probably unlikely to establish IVIVC
in such cases.I am not aware if any IVIVC study is documented for this.
Regards,
Pradeep Bhadauria
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The following message was posted to: PharmPK
To the PharmPK list:
For those who might be interested in a comparison
of the results of the method based on the f2 factor with the results
of the method proposed in our study
Dedik, L., Durisova, M. Computer Methods and Programs
in Biomedicine, 69, 2002, 49-55
I would recommend the URL
http://www.uef.sav.sk/In-vitro-dissolution.ppt
Similarity indicated by the f2 factor is highlighted by dark green
and similarity indicated by the proposed criteria by light green.
Regards,
Maria Durisova, PhD, DSc (Math/Phys)
Scientific Secretary
and
Head of Department of Pharmacokinetics
Institute of Experimental Pharmacology
Slovak Academy of Sciences
Dubravska cesta 9
841 04 Bratislava
Slovak Republic
Tel./Fax: +421 2 54775928
http://www.uef.sav.sk/durisova.htm
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