Authors:W. Engel, N. Eisenreich, M. Herrmann, and V. Kolarik
Time and temperature resolved X-ray diffraction was used for thermal analysis. Series of diffraction patterns were measured,
while the samples are heated/cooled stepwise or isothermally with freely selectable temperature programs.
The method was applied for the investigation of the phase transitions of ammonium nitrate and HMX (1,3,5,7-tetranitro-1,3,5,7-tetraaza-cyclooctane),
when the identification of phases was required. Its capability in the field of kinetics is demonstrated with the isothermal
investigation of the solid state reaction of ammonium nitrate with copper oxide and the non-isothermal investigation of the
high temperature corrosion of nickel, which was performed by means of a difference procedure. For obtaining structural details
peak fitting and Rietveld refinement were applied for the investigation of ammonium nitrate and HMX.
Authors:W. Engel, N. Eisenreich, M. Alonso, and V. Kolarik
The application of TRXRD for thermal analysis is demonstrated using examples of phase transitions, solid-state reactions and
high-temperature corrosion. The measuring system produces a series of diffraction patterns, which are evaluated by a difference
procedure that a reduces the data to curves comparable to DSC and TG curves and thus suited to kinetic evaluation.
Authors:D. Giron, M. Draghi, C. Goldbronn, S. Pfeffer, and P. Piechon
The local anesthetic drug tetracaine hydrochloride is described in the Europ. Pharmacopea with a melting point of 148°C or
with a range of 134 to 147°C due to the melting points of two other forms. The polymorphic behaviour of tetracaine hydrochloride
has been studied by using thermal treatments, storage at 92% r.h., crystallizations and equilibrations with saturated solutions.
Samples were characterized by X-ray diffraction, IR, thermal analysis and elemental analysis. Since some findings were difficult
to interpret, temperature resolved X-ray diffraction was used additionally for the understanding of the thermal behaviour
of tetracaine hydrochloride. In this study the polymorphic behaviour of some other local anesthetic drugs is compared.
Ten different forms of tetracaine hydrochloride: six anhydrous crystalline forms, an amorphous form, a hemihydrate, a monohydrate
and a tetrahydrate were identified. The relationships between all forms are given.
The heating curve of the commercial form 1 is very dependent on the heating rate. This anhydrous form 1 is the thermodynamic
stable modification at ambient temperature. The form 2 is reversibly enantiotrope to form 1. The four other modifications
called 3, 4, 5 and 6 are monotropes of form 1.
Only forms 1 and 5 are stable at ambient temperature. Form 1 is hygroscopic only at high humidity level of 92% r.h., form
5 is hygroscopic at 61% r.h. Both transform into the monohy-drate.
No polymorphic forms of tetracaine base, dibucaine hydrochloride, procaine hydrochloride or prilocaine hydrochloride were
The commercial form of bupivacaine hydrochloride is a monohydrate. Thermal treatment at 200°C gives one anhydrous form. As
demonstrated by temperature resolved X-ray diffraction two other forms are detected by heating and cooling processes between
100 and 170°C. Equilibrations and crystallization experiments show that solvates are easily obtained in different solvents.
Temperature resolved X-ray diffraction is a very efficient tool as a support to DSC for the identification of the transition
processes and interpretation of thermal events and thermodynamic relationships. Equilibration experiments are very adequate
to find out the thermodynamically stable form at ambient temperature (solvent mediated transitions).
Authors:A. Sykuła-Zając, E. Łodyga-Chruścińska, B. Pałecz, R. E. Dinnebier, U. J. Griesser, and V. Niederwanger
Temperature-resolved X-ray and DSC investigations
The thermal behavior of BupiHCl was compared with DSC results and temperature-resolvedX-raydiffraction data. The X-ray patterns of BupiHCl monohydrate
Authors:D. Giron, P. Piechon, C. Goldbronn, and S. Pfeffer
The polymorphic behaviour of the purine derivative MKS 492 was studied with investigations of suspensions of selected samples in different solvents and of samples obtained by crystallizations. The samples were analyzed by DSC, TG and X-ray diffraction. Six different crystalline modifications called A, B, B, C, D and E and an amorphous form were identified. Four pure crystalline modifications, A, B, C and D have been manufactured and characterized by DSC, X-ray, IR, solubilities, densities, hygroscopicity and dissolution measurements. The four forms A, C, D and E are monotrop to the form B. The form B is enantiotrop to the form B, which revealed the highest melting point of all known polymorphs. This form B is only stable at high temperature. Temperature resolved X-ray diffraction was very helpful for proper interpretation of the thermal events. The melting peaks of the forms A and C and the endothermic peak corresponding to the enantiotropic transition B into B occur in a narrow range of temperature. The form B which is the most stable one at room temperature has been chosen for further development. Quantitative methods to determine the content of the forms A, C and D in samples of form B or to determine the content of form A, B and D in form C have been developed by using X-ray diffraction. Limits of detection are 1 or 2%. For the quantitative determination of the amorphous fraction, X-ray diffraction and microcalorimetry are compared. For high amounts of the amorphous fraction, the X-ray diffraction method is preferred because it is faster. Microcalorimetry is very attractive for levels below 10% amorphous content. The lowest limit of detection is obtained by microcalorimetry, about 1%.
In order to complement the TG–MS results, in situ TR-XRD were done for the first time to probe the structure/stability of the phases formed during the
Conventional thermoanalytical techniques like TG, DTA and DSC do not tell the nature of the gaseous products. Evolved gas analysis (EGA) offers a useful tool to identify the fragments which cannot be detected by
Dried samples of ammonium nitrate (AN) containing 1, 3, 5 mol% KNO3, RbNO3 and CsNO3 were investigated with temperature resolved X-ray diffraction. The samples were cycled with 2 temperature programs from −70° to 100° and −70° to 150°C, resp. DSC measurements were made for comparison.
Several drug substances or excipients are hygroscopic. The uptake or loss of water of such substances is generally difficult
to control during processing or storage of drug products. DSC instruments with sub-ambient temperature equipment allow the
determination of the amount of freezable water by measuring the corresponding melting enthalpy.
The determination of freezable water adds valuable information complementary to TG analysis for understanding the processing
and storage of raw materials and drug products. Several substances were tested as is, without treatment, after storage at
92% r.h. and after equilibration with water. The results of these experiments showed that it was possible to demonstrate defined
hydrate formation, to determine the upper level of binding of water in amorphous substances and to confirm reversible hydrate
formations demonstrated by temperature resolved X-ray diffraction.
Investigations on the thermal behaviour of [Ni(en)3]C2O4·2H2O and [Ni(en)3]SO4 have been carried out in air and helium atmosphere. Simultaneous TG/DTA coupled online with mass spectroscopy (MS) in helium atmosphere detected the presence of H2, O, CO, N2/CH2=CH2 and CO2 fragments during the decomposition of tris(ethylenediamine)nickel(II) oxalate and H2, O, NH, NH2, NH3 and N2/CH2=CH2 fragments for tris(ethylenediamine)nickel(II) sulphate complex. The thermal events during the decomposition were monitored by temperature-resolved X-ray diffraction. In air, both the complexes give nickel oxide as the final product of the decomposition. In helium atmosphere, tris(ethylenediamine)nickel(II) oxalate gives nickel as the residue, whereas tris(ethylenediamine)nickel(II) sulphate gives a mixture of nickel and nickel sulphide phases as the final residue. Kinetic analyses of these complexes by isoconversional methods are discussed and compared.