Asian Journal of Pharmaceutical Analysis

The amorphous form of pharmaceutical materials represents a material’s most energetic solid state. It provides advantages in terms of dissolution rate and bioavailability. During the formulation process (like Micronisation, compaction, and blending,) predominantly crystalline materials are converted to amorphous fractions. The presence of a small amount of amorphous material is known or unknown to impact drug product performance. In-meter dose inhaler (MDI) and dry powder inhaler (DPI), dosage forms very low micron drug substance required. During Micronisation, the crystallinity of the drug substance in MDIs and DPIs can be affected by mechanical processing, including Micronisation. This can lead to the generation of amorphous thermodynamically unstable particles, which tend to convert to a more stable crystalline state. This recrystallization of micronized material could lead to uncontrolled particle growth, thereby affecting the critical quality attributes of the MDI or DPI product (e.g., aerosol particle size distribution (APSD) and delivered dose uniformity (DDU). Therefore, quantifying the amorphous fraction is essential to ensure the drug product meets its specifications. This paper discusses a complementary amorphous standard preparation technique and analytical technique that can quantify amorphous content accurately and precisely in many active pharmaceuticals. These techniques include Differential Scanning Calorimetry (DSC), FT-Raman, X-ray diffraction technique (XRPD), Modulated DSC (MDSC), Continuous Relative Humidity Perfusion Microcalorimetry, Dynamic Vapor Sorption (DVS), and Solution Calorimetry (SC).