Preparation and characterization of crystalline, semi-crystalline and fully amorphous powders of hydrophilic and lipophilic active pharmaceutical ingredients 1 2 1 2 1

T. Müller , J. Schiewe , R. Smal , C. Weiler , H. Steckel

Background: It is well known that standard pharmaceutical operations may lead to structural changes, crystal defects and amorphous regions of solid particles. Especially operations like milling, blending and even sieving generate these effects to excipients and active pharmaceutical ingredients (APIs). These disorders induce recrystallization and particle size change which have a
huge influence on drug delivery and product stability.  In this study a crystalline hydrophilic and lipophilic API is used for the preparation of semi-crystalline and fully amorphous samples and analysed by a variety of different analytical methods.
Methods: A ball-mill and a spray dryer were used to create fully amorphous samples. The study target was to find out differences between the production methods and differences in the behaviour of the contrasting APIs.  Furthermore the fully amorphous powders were used to quantify amorphous parts which were generated by micronization processes and blending.
Results: Both production processes (BM / SD) resulted in fully amorphous products and it was possible to characterize successfully crystalline, semi-crystalline and amorphous powders with different methods. In this analysis the completely amorphous ball-milled API was used for the preparation of a calibration curve with the help of the DVS. Because of this reason lower amorphous contents were found in micronized powders and in mixing tests with glass beads. It was possible to calculate amorphous parts between 0.55% and 5.04% depending on API and process method.
Conclusions: This study has shown that unit operations, such as blending, milling or micronization, may have a huge influence on physical state. Because of the resulting low sensitivity of the DVS method (water) for the hydrophobic batch there has to be established a DVS sorption method with organic solvent.

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