Transformation and Growth of Polymorphic Nuclei through Evaporative Deposition of Thin Films

Rapidly dip-coating a silicon substrate in an acetaminophen solution creates a thin film of polymorphic nuclei, and the relative amounts of each polymorph vary with the type of solvent. Polarized light microscopy (PLM) revealed that all films were initially amorphous and gradually crystallized over time scales of minutes to hours. Fourier transform infrared spectroscopy (FTIR) was used to identify the polymorphic form during crystallization and weeks after apparent stabilization of growth. Crystallites that initially nucleated from the amorphous films were found to be the metastable orthorhombic form. Over time, the orthorhombic crystallites stopped growing and the remaining amorphous regions transformed to the stable monoclinic form. The choice of solvent determined how fast the orthorhombic crystallites grew and thus controlled the polymorphic character of the film. For example, dip-coating from an ethanol solution produced a largely orthorhombic film, while water yielded a film with mixed character. Kinetic arguments are made to discuss these results in terms of relative nucleation rates, supersaturation, and evaporation rate of the solvent. We demonstrate that PLM and FTIR are suitable tools for exploring phase space with these thin films. This methodology might be applied broadly to polymorph screening and selection in evaluating pharmaceutical materials

Development of inert density mock materials for HMX

<p>Inert surrogates or mocks for high explosives are commonly used in place of the real material for complex experiments or in situations where safety is a concern. Here, several materials were tested as potential mocks for HMX in terms of density, thermal stability, and processability. Selection criteria were developed and a literature search was conducted primarily using the Cambridge Structural Database. Out of over 200 potentially acceptable materials, six were chosen for crystallization experiments and a suite of analytical characterization. Of these six, 5-iodo-2ˊ-deoxyuridine, <i>N,N</i>ˊ-bis(2,3,4,5,6-pentafluorophenyl)oxamide, and 2,3,4,5,6-pentafluorobenzamide all were found to be thermally stable at 150°C, matched HMX density as a pressed pellet, and could be crystallized to appropriate particle sizes. These three materials are considered suitable inert density mocks for HMX and will be the subject of future testing.</p

Probing Interfaces between Pharmaceutical Crystals and Polymers by Neutron Reflectometry

Pharmaceutical powder engineering often involves forming interfaces between the drug and a suitable polymer. The structure at the interface plays a critical role in the properties and performance of the composite. However, interface structures have not been well understood due to a lack of suitable characterization tool. In this work, we have used ellipsometry and neutron reflectometry to characterize the structure of such interfaces in detail. Ellipsometry provided a quick estimate of the number of layers and their thicknesses, whereas neutron reflectometry provided richer structural information such as density, thickness, roughness, and intermixing of different layers. The combined information allowed us to develop an accurate model about the layered structure and provided information about intermixing of different layer components. Systematic use of these characterization techniques on several model systems suggests that the nature of the polymer had a small effect on the interfacial structure, while the solvent used in polymer coating had a large effect. These results provide useful information on the efforts of engineering particle properties through the control of the interfacial chemistry