Abstrait

Applications of thermoanalytical techniques for studying polymorphism and solid-state transformations in pharmaceutical industry

Devkant Shandilya, Shatrughan Sharma

Knowledge of the polymorphic behavior of a drug is an essential requirement of drug formulation development in terms of its dissolution, bioavailability, stability and to a great extent the regulatory considerations. Polymorphic forms exhibiting different lattice structures tend to melt at different temperatures and therefore differential scanning calorimetry can be a unique tool in detecting these forms. The widespread uses of DSC within pharmaceutical research include polymorphism, pseudopolymorphism and glassy systems. The remarkable versatility of this technique is that the method essentially measures heat flow processes that are applicable to all systems and hence characterization of polymorphs with a far greater degree of sophistication. In developing a particular dosage form, there is a considerable interest in optimizing the removal of residual organic solvents. Understanding the nature of the binding of the volatile component and assessing the kinetics of the weight loss process, it is possible to get information on longer termstability. Thermogravimetric analysis along with DSC and X-ray diffraction techniques can be useful to obtain a more detailed analysis of the kinetics of desolvation processes such as dehydration and the nature of the drug-excipient or excipientsolvent interaction. More effective removal of solvent can be ascertained with appropriate kinetic analysis of loss process and TGA can be very useful in finalizing design of manufacturing protocols. This review gives representative examples of the widespread use of DSC and TGA to characterize polymorphs, solvates and investigate amorphous states. Examples outlined here envisage the thermodynamic parameters associated with polymorphic transitions and assessment of the relaxation behavior of amorphous pharmaceutical materials.