Selective Crystal Growth of Theophylline-Saccharin Cocrystal on Self-Assembled Monolayer from Incongruent System

Abstract

This paper seeks to extend the screening methods for cocrystal incongruent systems by using siloxane self-assembled monolayers (SAMs). The theophylline (THE)–saccharin (SAC)–methanol incongruent system was chosen as a case study. The results of cocrystallization experiments showed that siloxane SAMs with exposed Cl groups can act as templates for the selective growth of THE–SAC cocrystal on the monolayer surface with relatively high purity, which was confirmed by Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The observed selectivity is rationalized on the basis of two-dimensional geometric matching and chemical interactions at the SAM/crystal interfaces using a molecular modeling method.