Needle-Shaped Crystals: Causality and Solvent Selection Guidance Based on Periodic Bond Chains

Abstract

Needle-shaped crystals, typified by aspect ratios of (1:1:100–1000) are often the steady-state growth shapes in the crystallization of active pharmaceutical ingredients from solution. Crystals with such high aspect ratio shapes are troublesome in the subsequent processing steps required in the formation of a drug product. Therefore, the ability to design crystallizations that directly avoid the formation of needles is of significant interest. In this article, a causality for the formation of needles and guidance for solvent selection based on this causality are provided. The causality presented in this article was formed based on a spiral growth model and requires the presence of a single strongest periodic bond chain within the lattice that is parallel to the direction of elongation of the crystal. The article provides a method for predicting the formation of a needle for a given solute–solvent system based on this causality. Furthermore, three case studies are provided that demonstrate good agreement between experimentally obtained and predicted shapes. As a result, generalized guidance for solvent selection based on the objective of avoiding needles is provided.