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.

Sulfamerazine: Understanding the Influence of Slip Planes in the Polymorphic Phase Transformation through X-Ray Crystallographic Studies and ab Initio Lattice Dynamics

“…The main emphasis has been on the thermodynamics of the polymorph transformations and on mechanical properties such as millability, etc. (7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) Zhang et al reported that the thermodynamic transformation of Form II to Form I happens between 50-54 o C, (22) while in our previous work, we discovered that Form I goes to Form II on ball milling for an hour at room temperature. (8) Milling at low temperatures leads to the amorphization of both forms.…”

Synchrotron Radiation Pair Distribution Function Analysis of Gels in Cements

“…In order to obtain PDF patterns of very high quality, the recorded Q-range has to be large. For this reason, the use of short wavelength X-rays and high 2θ diffracting angles is very important [24]. Total scattering data analyzed by PDF methodology may distinguish phases that are amorphous, nanocrystalline, or crystalline, and this methodology provides quantitative information concerning phase contents and local bonding environments [21].…”

Amorphous silicate nanoparticles with controlled Fe-Mg pyroxene compositions

“…A semi-quantitative measure of the similarities between the ANP structures can be obtained from the PDF data [25] using the Pearson product-moment correlation, R, calculated pair-wise for all PDF datasets,…”

“…Thus R allows us to gauge how similar/dissimilar the structures are without knowing specific details of atomic coordinates and bond angles etc. [25].…”