Analyses of Multi- Phase Pharmaceuticals Using SImultaneous Differential Scanning Calorimetry and X-Ray Diffraction

Abstract

The analysis of multi-phase pharmaceuticals, particularly when similar structures are involved (i.e. polymorphs, salts or hydrates), can often be a difficult task. Historically, x-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) have been utilized to study pharmaceutical samples. Relative to other materials, diffraction data for pharmaceuticals are often complex due to the large number of diffraction maxima caused by the size of the molecule and/or the molecular symmetry. Multi-phase mixtures tend to have a large number of overlapping peaks which can hinder the difftactionist's ability to identify phases and interpret the data. When similar structures are analyzed calorimetrically, their thermal events may severely overlap (as will be shown), preventing accurate interpretation of the data. In addition there are several types of thermal events which may not be related to structural transitions. A common one in pharmaceuticals is the loss of solvent or absorbed (versus molecular) water.

A practical guide to pharmaceutical analyses using X-ray powder diffraction

“…These experiments can cause separation by melting/cooling with melt and recrystallization processes. A variety of commercial high-temperature equipment is available and dual instruments such as TGA-XRD (Berzins et al ., 2010) and DSC-XRD (Fawcett et al , 1986; Kishi and Toraya, 2004) are also useful. A simple drying oven can phase change hydrates and often add enough energy to crystallize components, providing clues to formulation ingredients.…”

Characterization of the Polymorphic Behavior of an Organic Compound Using a Dynamic Thermal and X-ray Powder Diffraction Technique

“…The DSC/XRPD experiments were performed in an inert atmosphere under either dry or humidified (70% RH) conditions. The DSC/XRPD instrument (shown in Figure ) was a Dow-developed technology , , which utilized a copper X-ray source and germanium monochromator to produce copper Kα 1 radiation at a wavelength of 1.540600 Å. The X-ray data was collected using an MBraun curved PSD with a chamber depth of 1 cm.…”

“…20,21 The variable temperature XRPD technique has been reviewed recently. 22,23 The present manuscript reports the use of a unique Dow-developed combined DSC/XRPD instrument [24][25][26] to dynamically characterize the polymorphic behavior of an organic compound API over a temperature range of hundreds of degrees. This allows the simultaneous measurements of thermochemical and thermophysical events, while following changes in crystalline structure (polymorphism) during these events.…”