engleski

Application of thermal analysis as screening tool for monitoring of amorphous phase content and compatibility study

The methods of thermal analysis, such as differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), are often used for physical characterization of active pharmaceutical ingredients (API). One of nonstandard methods of thermal characterization and investigation of API is microcalorimetry. In this work, two application examples of thermal analysis in pharmaceutical industry will be shown. The first of them is monitoring and quantification of the amorphous content in final micronized API material, and second application will be related to the study of compatibility between API and excipients by nonstandard microcalorimetry technique. During the micronization process, some small amounts of the amorphous phase can be formed, what can have negative influence on powder properties of the final product (such as agglomeration, flowability…). Because of this it is very important to develop the method that is sufficiently sensitive (low quantification limit) for monitoring of low amorphous content in the micronized samples. The XRD technique is often not sufficiently sensitive for quantification of small amorphous content, so for this purpose the methods of thermal analysis such as DSC or microcalorimetry are more suitable. In this research the development of DSC method for quantitation of amorphous content is shown that is based on quantification of heat of crystallization determined from non‐reversible heat flow signal. Microcalorimetry, frequently used for the study of polymorphic transformation and quantification of amorphous or some other crystal forms in API, can also be used as nonstandard technique for the compatibility study of API and excipients (such as mannitol, lactose monohydrate, cellulose, starch) used in formulation. As opposed to conventional methods for compatibility determination (XRD, DSC, TGA, FTIR, HPLC), which can take many weeks or months, the microcalorimetry experiment typically takes only a few hours what is a great advantage of this approach. Obtained results shows that the developed DSC method is highly sensitive for determination of low amorphous amount (quantification limit: 0.5%), and also that microcalorimetry is a powerful tool for the compatibility study.

thermal analysis ; differential scanning calorimetry (DSC) ; thermogravimetric analysis (TGA)

nije evidentirano