Title:Dipolar Reorientations in Amorphous Nimesulide: A TSDC and DSC Study
VOLUME: 14 ISSUE: 1
Author(s):Joaquim J. Moura Ramos and Hermínio P. Diogo
Affiliation:CQFM – Centro de Química- Física Molecular and IN − Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa
Keywords:Aging, DSC, dynamic fragility, secondary relaxations, TSDC.
Abstract:Background: The preparation of APIs in the amorphous solid form can be a means of circumventing
problems arising from poor solubility and low dissolution rate of the crystalline drugs.
However, molecular mobility can be responsible for the glass instability, so that the kinetic characterization
of the different relaxations that subsist in the amorphous solid is useful to allow define the conditions
for greater stability of the glassy pharmaceutical. Our purpose is to use the experimental techniques
of differential scanning calorimetry (DSC) and thermally stimulated depolarization currents
(TSDC) to study the thermal behavior of the pharmaceutical drug nimesulide and its slow molecular
mobility in the amorphous solid state.
Methods: DSC provides us a general view of the thermal behaviour of nimesulide and allows a general
kinetic characterization of its glass transition relaxation. TSDC allows isolating the individual modes of
motion present in nimesulide (in the temperature range between -150ºC and +15ºC). From the experimental
output of the TSDC experiments, the kinetic parameters associated with the different mobility
modes of motion were obtained, which allowed a detailed characterisation of the distribution of relaxation
times of the complex relaxations.
Results: No molecular mobility was detected below ∼ -30ºC. A sub-Tg relaxation, or secondary process,
was found by TSDC in the temperature region between ∼ -15ºC and ∼ +7ºC; this is a local mobility that
is affected by physical aging, and was attributed to a slow β-relaxation (Johari-Goldstein). The analysis
by DSC and TSDC of the α-relaxation showed that nimesulide is a moderately fragile
glass former. The dynamic fragility obtained by DSC was mDSC = 52 while that obtained by TSDC was
mTSDC = 70.
Conclusions: From the DSC study of the thermal behaviour we concluded that nimesulide has a moderate
glass forming ability and a week glass stability. The fact that the cold crystallization occurs only
some few tens of degrees above the glass transition temperature, and shows a slow kinetics, allowed the
study of the mobility by TSDC. TSDC thus proved to be an adequate technique to study the molecular
mobility in the amorphous nimesulide. However, the study by spectroscopic dielectric relaxation is
probably impossible under these conditions.
