Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids

Hot melt extruded transdermal films based on amorphous solid dispersions in Eudragit RS PO: The inclusion of hydrophilic additives to develop moisture-activated release systems

“…Interestingly, the formulation of FM3 films (low levels of methylcellulose) showed fine granules which may be related to ibuprofen crystals. Drug recrystallization in these samples was undetected using MTDSC or PXRD, suggesting that the small amount of crystalline material present may be below detection limits of these methods, which have been reported to be approximately 5% [37]. …”

Ionic Liquids Then and Now: From Solvents to Materials to Active Pharmaceutical Ingredients

“…Amorphous forms are of higher energy than crystalline compounds, 57 which allows them to have higher dissolution rates and solubilities, as there is no lattice structure to overcome or the need to inhibit solvation. However, amorphous solids have a tendency to crystallize spontaneously to a lower energy crystalline form at possibly inopportune times.…”

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

“…21,22 Thus, it is necessary to monitor and quantify the amount of amorphous phase during processing. Various analytical techniques have been used for the detection and quantification of amorphous content in solid-state pharmaceuticals, [23][24][25][26][27][28][29][30][31][32][33] such as X-ray powder diffraction (XRPD), [25][26][27] isothermal microcalorimetry (IMC), 28 differential scanning calorimetry (DSC), 29,30 solid-state nuclear magnetic resonance (NMR) 25,30 and vibrational spectroscopy. [31][32][33] While XRPD is the classic technique for the analysis of the solid state it however suffers from various problems including the influence of preferred crystal orientation, packing and sample preparation parameters on measured intensity.…”

“…[31][32][33] While XRPD is the classic technique for the analysis of the solid state it however suffers from various problems including the influence of preferred crystal orientation, packing and sample preparation parameters on measured intensity. 24 In contrast to XRPD, which probes the orderly arrangement of molecules in the crystal lattice, vibrational spectroscopy probes differences in chemical bonding 4 (usually H-bonding and other weak interactions) in the solid state of the API. With the help of a variety of chemometric and statistical techniques, a range of spectroscopic methods have been successfully used for the qualitative and quantitative analysis of pharmaceutical products.…”