Caiyun Ma

Refinement of hydrogen atomic position in a hydrogen bond using a combination of solid-state NMR and computation.

DFT computations of the proton chemical shift for the intermolecular hydrogen bond in the white form of methylnitroacetanilide, together with the experimental value obtained by high-speed magic-angle spinning NMR, enable the N-H distance to be determined as 1.03 +/- 0.02 A.

An examination of binding motifs associated with inter-particle interactions between facetted nano-crystals of acetylsalicylic acid and ascorbic acid through the application of molecular grid-based search methods

Grid-based intermolecular search methods using atom-atom force fields are used to assess the structural nature of potential crystal-crystal interfacial binding associated with the examination of representative pharmaceutical formulation components, viz acetylsalicylic acid (aspirin) and ascorbic acid (vitamin C). Molecular models of nano-sized molecular clusters for these two compounds, shaped in accordance with an attachment energy model of the respective particle morphologies, are constructed and used together with a grid-based search method to model the likely inter-particle interactions. The most-stable, mutual alignments of the respective nano-clusters based on their interaction energies are identified in the expectation that these are indicative of the most likely inter-particle binding configurations. The stable inter-particle binding configurations identified reveal that the number of interfacial hydrogen bonds formed between the binding particles is, potentially, an important factor in terms of the stability of inter-particle cohesion. All preferred inter-particle alignments are found to involve either the (1 0 0) or the (1 1 0) face of aspirin crystals interacting with a number of the growth forms of ascorbic acid. Four main types of interfacial hydrogen bonds are found to be associated with inter-particle binding and involve acceptor-donor interactions between hydroxyl, carbonyl, ester and lactone acceptor groups and hydroxyl donor groups. This hydrogen bonding network is found to be consistent with the surface chemistry of the interacting habit faces with, in general, the number of hydrogen bonds increasing for the more stable alignments. The likely usefulness of this approach for predicting solid-state formulation properties is reviewed.

Shape—The final frontier

Abstract Organic crystals grown from solution are known to exhibit multiple morphology and habits which are of great importance to the end use properties of the product such as the bioavailability and down stream processing such as in filtration and drying. The crystal morphology can also dictate other quality measures such as size. This paper reviews recent developments in on-line crystal morphology measurement and control using on-line imaging and image analysis. On-line imaging was found to be able to capture with high fidelity crystal shape and polymorphic transitions in real-time. The images were analyzed using a multi-scale image analysis method to extract the crystals from the image background. Preliminary results on estimating crystal growth rates and kinetics parameters for different facets for rod-like crystals were presented. The paper also reviewed recent developments in morphological population balance (PB) modelling which can provide the evolution of the shape and distributions of sizes in all crystal face directions in a reactor. Finally, the perspectives for automatic morphology control which require integration of crystal morphology prediction, morphological PB modelling, on-line 3D imaging and image analysis for shape characterisation as well as computational fluid dynamics are outlined.