Page 38 - Pharmaceutical Solution for Pharma Analysis

LAAN-A-TA-E016

Application Thermal Analysis

News Polymorphism of Drugs

No.T152

Q Introduction DSC
mW
Polymorphism is the phenomenon of materials with the
same chemical structure having different crystalline 176.2 ˚C
structures. The different crystal forms of polymorphic 0.0 173.7 ˚C 189.5 ˚C
materials have different properties, including solubility
and stability, so evaluating polymorphism is an 175.1 ˚C
-5.0
important part of drug development. Differential heat of fusions: -106.6 J/g
scanning calorimetry (DSC) is an effective technique for
investigating polymorphism that requires no sample
-10.0
pretreatment and performs measurements quickly. DSC
can be used to evaluate polymorphism based on
different crystal shapes having different melting points 190.8 ˚C
-15.0
and heat of fusions. Here, we describe an example use 50 100 150 200
of DSC to analyze polymorphs. Temp [˚C]
Fig. 1 DSC Measurement of Carbamazepine Form ᶗ

Q Measurement of Carbamazepine DSC
mW
Carbamazepine is used as an anticonvulsant and is
known to exist in multiple crystal forms. Carbamazepine 189.6 ˚C
form ᶗ (Fig. 1) and form ᶙ (Fig. 2) were analyzed. A sharp 0.0
endothermic peak can be observed with both forms at
around 190 ˚C. This peak represents the melting of
crystal form ᶙ. An endothermic/exothermic peak is -5.0 heat of fusions: -102.8 J/g
visible between 170 ˚C and 180 ˚C with crystal form ᶗ.
This phenomenon is speculated to be caused by
-10.0
recrystallization of formᶗ to stable form ᶙ following
melting.
190.7 ˚C
-15.0
100 200
Temp [˚C]
Fig. 2 DSC Measurement of Carbamazepine Form ᶙ
Q Measurement of Sulfapyridine DSC
mW
Sulfapyridine was heated to 205 ˚C (first run), then
cooled and heated again (second run) (Fig. 3).
During the first run, only the melting peak of a 0.00 1st run 101.0 ˚C
stabilized phase is visible at 192.2 ˚C, while during the
second run, there is a glass transition at 54.7 ˚C, a Onset : 54.7 ˚C
End-set : 64.0 ˚C
crystallization peak at 101 ˚C, and the melting peak of Midpoint : 57.2 ˚C
a quasi-stable phase at 181.9 ˚C. -10.00 2nd run 174.6 ˚C 192.1 ˚C

192.2 ˚C
181.9 ˚C
-20.00
50 100 150 200
Temp [˚C]
Fig. 3 DSC Measurement of Sulfapyridine