The object of the present work is to study the thermal characteristics of indinavir sulfate and to evaluate the quality of
the raw materials. Indinavir A, B, C and reference samples were obtained from different suppliers and submitted to TG, DSC
and DSC-photovisual analyses. TG/DTG curves indicated a desolvation and dehydration processes and were confirmed by DSC. According
to the DSC curves the fusion took place at about 141–142°C for indinavir C and Reference sample B and about 146–149°C for
the others. DSC-photovisual showed insoluble raw materials for indinavir C at 160°C. Indinavir sulfate is highly hygroscopic
drug which requires attention during storage and manufacture by pharmaceutical industry.
Manufacturing processes may involve the presence of water in the crystallization of the drug substance or in manufacturing
or in the composition of the drug product through excipients. Dehydration steps may occur in drying, milling, mixing and tabletting
processes. Furthermore, drug substances and drug products are submitted to different temperatures and relative humidities,
due to various climatic conditions giving rise to unexpected hydration or dehydration aging phenomena. Therefore the manufacture
and the characterization of hydrates is part of the study of the physical properties of drug substances.
Several hydrates and even polymorphic forms thereof can be encountered. Upon dehydration crystal hydrates may retain more
or less their original crystal structure, they can lose crystallinity and give anamorphous phase, they can transform to crystalline
less hydrated forms or to crystalline anhydrous forms.
The proper understanding of the complex polyphasic systemhydrates–polymorphs–amorphous state needs several analytical methods.
The use of techniques such as DSC-TG, TG-MS, sorption-desorption isotherms, sub-ambient experiments, X-ray diffraction combined
with temperature or moisture changes as well as crystal structure and crystal modelling in addition to solubilities and dissolution
experiments make interpretation and quantitation easier as demonstrated with some typical examples.
Thermal analysis methods are well-established techniques in research laboratories of pharmaceutical industry. The robustness
and sensitivity of instrumentation, the introduction of automation and of reliable software according to the industrial needs
widened considerably the areas of applications in the last decade. Calibration of instruments and validation of results follow
the state of the art of cGMP as for other analytical techniques. Thermal analysis techniques are especially useful for the
study of the behavior of the poly-phasic systems drug substances and excipients and find a unique place for new delivery systems.
Since change of temperature and moisture occur by processing and storage, changes of the solid state may have a considerable
effect on activity, toxicity and stability of compounds. Current requirements of the International Conference of Harmonisation
for the characterization and the quantitation of polymorphism in new entities re-enforce the position of thermal analysis
techniques. This challenging task needs the use of complementary methods. Combined techniques and microcalorimetry demonstrate
their advantages. This article reviews the current use of thermal analysis and combined techniques in research and development
and in production. The advantage of commercially coupled techniques to thermogravimetry is emphasized with some examples.
substance, or, (c) yielding a new crystal with fewer or no solvent/water molecules [ 6 – 13 ].
At room temperature (r.t.), paroxetine hydrochloride can be obtained (with different synthesis procedures) in two crystalline forms, called pseudo-polymorphs
different solid phases that may occur during crystallization and pharmaceutical formulation processes, i.e. polymorphs, pseudo-polymorphism, solvates, desolvated solvates and amorphous materials is therefore advisable for both drugs and excipients. It is