Toward Phase Quantification at the Nanoscale Using the Total Scattering Pair Distribution Function (TSPDF) Method: Recrystallization of Cryomilled Sulfamerazine

Abstract

One of the most challenging problems facing the pharmaceutical industry is to identify and quantify the phase fractions in mixed phase samples that contain crystalline, nanocrystalline, and amorphous components. Here we demonstrate an approach that accomplishes this using high energy X-rays coupled with total scattering pair distribution function (TSPDF) analysis by studying samples of sulfamerazine, a sulfonamide antibiotic drug, recrystallizing from a cryomilled-induced amorphous state. Samples milled under different conditions were shown to have significantly different phase compositions. The initial amorphous state was obtained by cryomilling the stable Form 1 polymorph. This was then aged at low temperature to initiate controlled recrystallization. We show that depending on the milling and aging protocol we see a mixture of amorphous material with the metastable Form 2 polymorph. A minority of Form 1 is also observed. We describe the approach that allowed us to quantify the phase fractions despite the majority of the sample lacking crystalline order.