Prediction of the Mechanical Deformation Properties of Organic Crystals Based upon their Crystallographic Structures: Case Studies of Pentaerythritol and Pentaerythritol Tetranitrate.

Purpose: Development of a quantitative model and associated workflow for predicting the mechanical deformation properties (plastic deformation or cleavage fracture) of organic single crystals from their crystallographic structures using molecular and crystallographic modelling.

Methods: Intermolecular synthons, hydrogen bonding, crystal morphology and surface chemistry are modelled using empirical force fields with the data integrated into the analysis of lattice deformation as computed using a statistical approach.

Results: The approach developed comprises three main components.

Crystallographic Structure, Intermolecular Packing Energetics, Crystal Morphology and Surface Chemistry of Salmeterol Xinafoate (Form I).

Single crystals of salmeterol xinafoate (form I), prepared from slow cooled supersaturated propan-2-ol solutions, crystallize in a triclinic P1¯ symmetry with 2 closely related independent salt pairs within the asymmetric unit, with an approximately double-unit cell volume compared with the previously published crystal structure. Synthonic analysis of the bulk intermolecular packing confirms the similarity in packing energetics between the 2 salt pairs. The strongest synthons, as expected, are dominated by coulombic interactions.

Formulation pre-screening of inhalation powders using computational atom-atom systematic search method.

The synthonic modeling approach provides a molecule-centered understanding of the surface properties of crystals. It has been applied extensively to understand crystallization processes. This study aimed to investigate the functional relevance of synthonic modeling to the formulation of inhalation powders by assessing cohesivity of three active pharmaceutical ingredients (APIs, fluticasone propionate (FP), budesonide (Bud), and salbutamol base (SB)) and the commonly used excipient, α-lactose monohydrate (LMH).