# PharmPK Discussion - Korsemeyer peppas constant

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• On 19 Jul 2005 at 13:23:30, "Ketan Maheshbhai Ranch" (ketan.ranch.-a-.ranbaxy.com) sent the message

The following message was posted to: PharmPK

Dear all,

How to calculate Korsemeyer peppas constant and n value for the data
of in vitro drug release from formulation, and what is its importance
to interpret the in vitro dissolution data and does it indicate the
mechanism of drug release from the formulation.

Regards
Ketan

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• On 19 Jul 2005 at 15:44:35, "MURAD R. MELHEM" (melhemmr.at.email.uc.edu) sent the message

The following message was posted to: PharmPK

Dear Ketan,
Assuming that the polymeric formulation is non-swellable and
non-degradable, the Peppas equation refers to mechanisms of
relesae as Fickian and non-Fickian. A simple equation
relation an exponential time factor (n) to the cumulative
amount of loaded drug released was originally suggested by
Peppas at al.

Here is the original but very useful reference:

Pharm Acta Helv. 1985;60(4):110-1.

Analysis of Fickian and non-Fickian drug release from
polymers.

Peppas NA.

Hope this helps.

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• On 19 Jul 2005 at 13:09:38, marival bermejo (bibilina.aaa.yahoo.com) sent the message

The following message was posted to: PharmPK

Q=b + Kp*t**n
In this equation Q represents the percent of drug
released at time t ; Kp is constant incorporating
structural and geometric characteristics of the
release device, and n is the release exponent
indicative of the mechanism of release. When n
approaches 0.5, a Fickian /diffusion-controlled
release is implied, where 0.5 < n < 1.0 non-Fickian
transport and n=1 or near 1 for zero-order ; b
corresponds to the intercept accommodating the burst
effect..
You can obtain the parameters by non linear regression
of the amounts dissolved (percent released) versus
time

Korsmeyer R.W., Gurney R., Doelker E., Buri P., Peppas
N.A. (1983) Mechanisms of solute release from porous
hydrophilic polymers. J. Pharm. Sci., 15: 25-35.

regards
marival

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• On 19 Jul 2005 at 13:12:39, Vlase Laurian (vlaselaur.-at-.yahoo.com) sent the message

Hi,
1. the best method is to fit the dissolution equation in WNL as it,
%Dis=k*(time**n); constrain n between 0.3 and 1.2 with initial 0.5
2. for better initial estimate of param, do log liniarisation of
equation, exp-intercept is k and slope is n
3. maybe you have to consider some alternatives for data analysis, in
many instances you will obtain a better fit using a mixed order kinetic
release mechanism (0 order + 1st order, different lag times)
4. with either method, usually you can obtain a good fit for %dis up to
75-85%
regards,
laurian vlase

Vlase Laurian
MD, PhD, Pharm. Chem.
Teaching Assistant
Dept. of Pharmaceutical Technology and Biopharmaceutics
Faculty of Pharmacy
University of Medicine and Pharmacy "Iuliu Hatieganu"
13, Emil Isac
Cluj-Napoca, Cluj 400023, Romania
email:vlaselaur.-at-.yahoo.com

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• On 20 Jul 2005 at 10:50:46, "Frank Bales" (frankbales.at.msn.com) sent the message

The following message was posted to: PharmPK
Dear Vlase, Regarding fitting dissolution and Korsemeyer peppas constant

Yes, Vlase, I have seen good fits up to about 80% as you suggest. I
have looked for a reference to justify not going closer to 100%. Do
you know of a reference?

Regards,

Frank
Frank Bales

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• On 23 Jul 2005 at 01:54:08, Vlase Laurian (vlaselaur.-a-.yahoo.com) sent the message

Hi,
you cannot obtain a fit up to 100% with Peppas or Higuchi.
If you look at the formula, for t is inf you get %dis is inf, which
is not possible.
Besides, if you consider Peppas relation on all the diss process,
this process will stop suddenly at 100%, which is also not realistic.
you can try a 1st order release model for the rest of 15-20% diss and
let WNL to calculate also the time for switching from Peppas to 1st
order process. (you will have two more param on final model, time of
switching and k1)
regards,
laurian

Vlase Laurian
MD, PhD, Pharm. Chem.
Teaching Assistant
Dept. of Pharmaceutical Technology and Biopharmaceutics
Faculty of Pharmacy
University of Medicine and Pharmacy "Iuliu Hatieganu"
13, Emil Isac
Cluj-Napoca, Cluj 400023, Romania
email:vlaselaur.-a-.yahoo.com

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