Prediction of the Effect of Solvents and Impurities/Additives on Crystal Shape and Growth Kinetics

Publication Reference: 
Author Last Name: 
Carl J. Tilbury and Michael F. Doherty
Report Type: 
ARR - Annual Report
Research Area: 
Particle Formation
Publication Year: 
Publication Month: 
United States

Executive Summary
In the first year of this project we have used IFPRI funds to redesign and rewrite our crystal growth and
morphology software tool in order to generalize the methodology to a much broader class of industrially
important solid forms, and especially drug substances. We call our software design aid Addict (Ad-
vanced Design and Development of Industrial Crystallization Technology). Our goal is to produce a
shape-prediction design aid that is applicable to all crystalline solids, from organic molecules to organic
salts, cocrystals and solvates. A necessary, but not sufficient, condition to enact mechanistic crystal
growth models is to calculate and organize solid-state interactions between growth units. The typical
architecture for acquiring this information is to apply crystallographic operations to generate a unit cell
from the asymmetric unit. While this approach is feasible for systems where the asymmetric unit corre-
sponds to the growth unit itself, many systems do not satisfy this criterion (including all organic salts,
solvates and cocrystals). With our redesigned input preparation architecture, we can build a description
of the solid-state interactions that is independent of the asymmetric unit and applicable to any crystal-
lographic complexity. We are currently implementing this redesign within the software. Although it re-
quires a complete rewrite of the existing codes, these modifications lay the groundwork for rapid in sili-
co habit predictions of organic salts, cocrystals and solvates grown from solution.
Upon completion of this new architecture, we will demonstrate improved functionality by testing
ADDICT v3.0 against molecular crystals with multiple molecules in the asymmetric unit. Following this,
we plan to continue with the remaining modifications required to implement models for organic salts,
hydrates/solvates, and cocrystals crystallized from solution.