THERMALHelp needed
Bob Behme
thermal@egr.msu.edu
Wed, 11 Dec 2002 10:35:53 -0600
Dear Dr. A. Tahraoui,
If you polymorphs, first determine how many polymorphs there are. Secondly,
characterize each pair as either monotropic or enantiotropic. Monotropism
means the higher melting form is thermodyamically more stable than the other
form at all temperatures below their melting points. Enantiotropism means
there is a temperature below their melting points where their relative
physical stability changes; then it necessary to know where this transition
temperature is relative to room temperature.
In my opinion, Differential Scanning Calorimetry is the best way to
characterize polymorphs as either monotropic or enantiotropic. DSC can
estimate heats of fusion and melting points of each polymorph even if
polymorph undergoes multiple phase changes during the analysis (J. Pharm.
Sci., Vol 80, No 10, October 1991, pp 986-990). With calorimetry data, one
can construct Gibbs-Free energy plots that reveal the relative physical
stability for each polymorphic pair below their melting points and
transition temperatures for enantiotrops. Estimating heats of fusion of
meta-stable polymorphs and constructing free-energy plots is a daunting task
the first time you do it. There is a plethora of information in the
pharmaceutical literature about characterizing polymorphism, some much
better than others.
I assumed your shelf-life question was related to physical stability of
polymorphs, not chemical stability of the drug entity. Thermal methods and
spectroscopic methods theoretically can quantify polymorphs in final dosage
forms. These methods can measure rates of conversion of one form to other
forms during storage.
Additional Information at: http://www.dsc-tga-dma-lab.com/polymorphism.htm
and/or http://www.dsc-tga-dma-lab.com/Capabilities.htm. You may contact me
directly, rather than through the Thermal News Group.
Bob Behme (email: behme@evansville.net)
Science Resources, Inc.
2029 Washington Ave, Suite 201
Evansville, IN 47714-2257
USA
812-473-0125
http://www.dsc-tga-dma-lab.com
-----Original Message-----
From: thermal-admin@egr.msu.edu [mailto:thermal-admin@egr.msu.edu]On
Behalf Of ceas32
Sent: Wednesday, December 11, 2002 3:39 AM
To: thermal@egr.msu.edu
Subject: THERMALHelp needed
THERMAL NEWS GROUP: Hi there,
I wonder if someone out there can help me?
I have got a Mettler-Toledo DSC 821 with ADSC capabilities and I would like
to use it to estimate the shelf life of formulation drugs. what can I do?
What should I focus on? how should I set my experiment(s)? Is glass
transition enough? Then How?..
Can someone tell me whether the stability of a drug is increased if
transform from crystalline form to poplymorph form? Any good literature on
both subjects?
Thank you very much for you help
Dr A. Tahraoui
Senior Formulation Scientist
Propharma Ltd
204 George Street
Glasgow G1 1XW, UK
Tel: +44 141 5484925
Fax: +44 141 548 4938
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<DIV><FONT face=Arial size=2>Hi there,</FONT></DIV>
<DIV><FONT face=Arial size=2></FONT> </DIV>
<DIV><FONT face=Arial size=2>I wonder if someone out there can help
me?
</FONT></DIV>
<DIV><FONT face=Arial size=2></FONT> </DIV>
<DIV><FONT face=Arial size=2>I have got a Mettler-Toledo DSC 821 with ADSC
capabilities and I would like to use it to estimate the shelf life of
formulation drugs. what can I do? What should I focus on? how should I
set
my experiment(s)? Is glass transition enough? Then How?..</FONT></DIV>
<DIV><FONT face=Arial size=2></FONT> </DIV>
<DIV><FONT face=Arial size=2>Can someone tell me whether the stability of a
drug
is increased if transform from crystalline form to poplymorph
form?
Any good literature on both subjects?</FONT></DIV>
<DIV><FONT face=Arial size=2></FONT> </DIV>
<DIV><FONT face=Arial size=2>Thank you very much for you help</FONT></DIV>
<DIV><FONT face=Arial size=2></FONT> </DIV>
<DIV><FONT face=Arial size=2></FONT> </DIV>
<DIV><FONT face=Arial size=2>Dr A. Tahraoui<BR>Senior Formulation
Scientist<BR>Propharma Ltd<BR>204 George Street<BR>Glasgow G1 1XW,
UK</FONT></DIV>
<DIV> </DIV>
<DIV><FONT face=Arial size=2>Tel: +44 141 5484925<BR>Fax: +44 141 548
4938</FONT></DIV></BODY></HTML>
_______________________________________________
THERMAL mailing list
THERMAL@egr.msu.edu
http://www.egr.msu.edu/mailman/listinfo/thermal
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<DIV><FONT face=Arial color=#0000ff></FONT><FONT face=Arial
color=#0000ff></FONT><FONT size=2>Dear Dr. A. Tahraoui,</FONT></DIV>
<DIV><FONT size=2></FONT> </DIV>
<DIV><FONT size=2>If you polymorphs, first determine how many
polymorphs there are. Secondly, characterize each
pair as either monotropic or enantiotropic. Monotropism
means the higher melting form is thermodyamically more stable than the
other form at all temperatures below their melting points. Enantiotropism
means there is a temperature below their melting points where their
relative physical stability changes; then it necessary to know
where this transition temperature is relative to room temperature.
</FONT></DIV>
<DIV><FONT size=2></FONT> </DIV>
<DIV><FONT size=2>In my opinion, Differential Scanning Calorimetry is the best
way to characterize polymorphs as either monotropic or
enantiotropic. DSC can estimate heats of fusion and melting
points of each polymorph even if polymorph undergoes multiple
phase changes during the analysis (J. Pharm. Sci., Vol 80, No 10, October
1991, pp 986-990). With calorimetry data, one can construct
Gibbs-Free energy plots that reveal the relative physical stability
for each polymorphic pair below their melting points and transition
temperatures for enantiotrops. Estimating heats of fusion of
meta-stable polymorphs and constructing free-energy plots is
a daunting task the first time you do it. There is a
plethora of information in the pharmaceutical literature about
characterizing polymorphism, some much better than others. </FONT></DIV>
<DIV><FONT size=2></FONT> </DIV>
<DIV><FONT size=2>I assumed your shelf-life question was related to
physical stability of polymorphs, not chemical stability of the drug
entity. Thermal methods and spectroscopic
methods theoretically can quantify polymorphs in
final dosage forms. These methods can measure rates of
conversion of one form to other forms during storage.</FONT></DIV>
<DIV><FONT size=2></FONT> </DIV>
<DIV><FONT size=2>Additional Information at: <A
href="http://www.dsc-tga-dma-lab.com/polymorphism.htm">http://www.dsc-tga-dma-lab.com/polymorphism.htm</A> and/or
<A
href="http://www.dsc-tga-dma-lab.com/Capabilities.htm">http://www.dsc-tga-dma-lab.com/Capabilities.htm</A>.
You may contact me directly, rather than through the Thermal News
Group. </FONT></DIV>
<DIV><FONT face=Arial color=#0000ff size=2></FONT><BR></DIV><FONT size=2>
<DIV>
<DIV><FONT size=2></FONT></DIV>
<DIV><FONT face=Arial size=2>Bob Behme (email: <A
href="mailto:behme@evansville.net">behme@evansville.net</A>) </FONT></DIV>
<DIV><FONT face=Arial size=2>Science Resources, Inc.</FONT></DIV>
<DIV><FONT face=Arial size=2>2029 Washington Ave, Suite 201</FONT></DIV>
<DIV><FONT face=Arial size=2>Evansville, IN 47714-2257</FONT></DIV>
<DIV><FONT face=Arial>USA</FONT></DIV>
<DIV><FONT face=Arial size=2>812-473-0125</FONT></DIV>
<DIV><FONT face=Arial size=2><A
href="http://www.dsc-tga-dma-lab.com/">http://www.dsc-tga-dma-lab.com</A></FONT></DIV>
<DIV><FONT face=Arial size=2></FONT> </DIV></FONT><FONT
size=2><BR><BR>-----Original Message-----<BR>From: thermal-admin@egr.msu.edu
[</FONT><A href="mailto:thermal-admin@egr.msu.edu"><FONT
size=2>mailto:thermal-admin@egr.msu.edu</FONT></A><FONT size=2>]On<BR>Behalf Of
ceas32<BR>Sent: Wednesday, December 11, 2002 3:39 AM<BR>To:
thermal@egr.msu.edu<BR>Subject: THERMALHelp needed<BR><BR><BR>THERMAL NEWS
GROUP: Hi there,<BR><BR>I wonder if someone out there can help
me? <BR><BR>I have got a Mettler-Toledo DSC 821 with ADSC capabilities and
I would like to use it to estimate the shelf life of formulation drugs.
what can I do? What should I focus on? how should I set my experiment(s)? Is
glass transition enough? Then How?..<BR><BR>Can someone tell me whether the
stability of a drug is increased if transform from crystalline form to
poplymorph form? Any good literature on both subjects?<BR><BR>Thank
you very much for you help<BR><BR><BR>Dr A. Tahraoui<BR>Senior Formulation
Scientist<BR>Propharma Ltd<BR>204 George Street<BR>Glasgow G1 1XW,
UK<BR><BR>Tel: +44 141 5484925<BR>Fax: +44 141 548 4938<BR><!DOCTYPE HTML
PUBLIC "-//W3C//DTD HTML 4.0
Transitional//EN"><BR><HTML><HEAD><BR><META
http-equiv=Content-Type content="text/html; charset=iso-8859-1"><BR><META
content="MSHTML 5.50.4134.600"
name=GENERATOR><BR><STYLE></STYLE><BR></HEAD><BR><BODY
bgColor=#ffffff><BR><DIV><FONT face=Arial size=2>Hi
there,</FONT></DIV><BR><DIV><FONT face=Arial
size=2></FONT>&nbsp;</DIV><BR><DIV><FONT face=Arial
size=2>I wonder if someone out there can help
me?&nbsp;<BR></FONT></DIV><BR><DIV><FONT face=Arial
size=2></FONT>&nbsp;</DIV><BR><DIV><FONT face=Arial
size=2>I have got a Mettler-Toledo DSC 821 with ADSC<BR>capabilities and I
would like to use it to estimate the shelf life of<BR>formulation
drugs.&nbsp; what can I do? What should I focus on? how should I set<BR>my
experiment(s)? Is glass transition enough? Then
How?..</FONT></DIV><BR><DIV><FONT face=Arial
size=2></FONT>&nbsp;</DIV><BR><DIV><FONT face=Arial
size=2>Can someone tell me whether the stability of a drug<BR>is increased if
transform from crystalline form to poplymorph form?&nbsp;&nbsp;<BR>Any
good literature on both
subjects?</FONT></DIV><BR><DIV><FONT face=Arial
size=2></FONT>&nbsp;</DIV><BR><DIV><FONT face=Arial
size=2>Thank you very much for you
help</FONT></DIV><BR><DIV><FONT face=Arial
size=2></FONT>&nbsp;</DIV><BR><DIV><FONT face=Arial
size=2></FONT>&nbsp;</DIV><BR><DIV><FONT face=Arial
size=2>Dr A. Tahraoui<BR>Senior
Formulation<BR>Scientist<BR>Propharma Ltd<BR>204 George
Street<BR>Glasgow G1
1XW,<BR>UK</FONT></DIV><BR><DIV>&nbsp;</DIV><BR><DIV><FONT
face=Arial size=2>Tel: +44 141 5484925<BR>Fax: +44 141
548<BR>4938</FONT></DIV></BODY></HTML><BR>_______________________________________________<BR>THERMAL
mailing list<BR>THERMAL@egr.msu.edu<BR></FONT><A
href="http://www.egr.msu.edu/mailman/listinfo/thermal" target=_blank><FONT
size=2>http://www.egr.msu.edu/mailman/listinfo/thermal</FONT></A><BR></DIV></BODY></HTML>