Improving Mechanical Properties of Caffeine and Methyl Gallate Crystals by Cocrystallization

Abstract

By the formation of a 1:1 cocrystal of caffeine and methyl gallate, we demonstrated that powder compaction properties could be profoundly improved. The selection criterion for cocrystal exhibiting superior compaction properties was the presence of slip planes in crystal structure. Bulk cocrystal was prepared by suspending powders of the two pure compounds in ethanol. Fine powders of similar particle size distribution were compressed. Within the whole range of compaction pressure, the tablet tensile strength of methyl gallate was very poor (<0.5 MPa) and severe lamination and sticking occurred in almost all tablets. Tabletability of caffeine was acceptable at <150 MPa. However, at >180 MPa, severe lamination of caffeine tablets suddenly occurred. Tablet tensile strength dropped sharply at >240 MPa. In contrast, the tabletability of the cocrystal was excellent over the entire pressure range. Tablet tensile strength of the cocrystal was ∼2 times that of caffeine at <200 MPa, and the ratio gradually increased with increasing pressure, e.g., ∼8 fold at 350 MPa. Poor tablet tensile strength was always associated with high elastic recovery and low plasticity. The good plasticity and tabletability of the cocrystal validated the selection criterion, i.e., the presence of slip planes in crystal structure.