Milling is frequently used in pharmaceutical processing to achieve particle size reduction to enhance the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). The intent is to achieve particles with favorable size distributions that enhance dissolution rates due to their increased surface areas. Milling may also be used to obtain a consistent particle size distribution of the API for ensuring content uniformity of the dosage form. Micronization, the milling operation discussed in this work, is achieved through a high energy air-jet milling process, whereby fast moving API particles are forced to collide, resulting in particle size reduction. Significant attrition is achieved through this process, but significant structural and surface changes are often induced. These changes potentially affect the stability and physicochemical properties of the API, as well as the performance of the formulated product. Generally, milled materials demonstrate unique physical properties, e.g. crystallization onset temperature, compared to bulk amorphous materials [1 -4]. In this work, we characterize amorphous and micronized APIs using differential scanning calorimetry (DSC), solid state nuclear magnetic resonance (SSNMR), gravimetric vapor sorption (GVS), and X-ray powder diffraction (XRPD) to obtain a thorough understanding of the components of the micronization-induced changes.
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