Material Impurity Distribution of Lattice-Incorporated Impurities in Salicylic Acid
Rattavut Teerakapibal, Huayu Li, Brian Linehan, Fredrik L. Nordström
Abstract
The mechanisms of purging structurally similar impurities in solution crystallization have been evaluated using the model compound salicylic acid. Of the 11 added impurities, 3 showed appreciable entrapment in the solid phase: viz., salicylamide, anthranilic acid, and benzoic acid. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and the use of a previously reported solubility-limited impurity purge (SLIP) test have shown that the impurities are entrapped by a lattice incorporation mechanism. Impurities become integrated within the product crystals during the crystallization by forming terminal solid solutions. Most of the impurity entrapment was found to take place very early in the crystallization, immediately after seeding. The least entrapment occurred at the end of the crystallization, despite the mother liquor being enriched in impurities. These changes caused purity variations in the solids, which were not properly captured by the average value. A mathematic framework was developed to afford the material impurity distribution (MID), which represents the mass-based impurity profile across a material based on the SLIP test. It is shown that the level of impurities in the crystallized material is far from constant and in fact varies by orders of magnitude, in many cases by more than 20 times. These differences give rise to changes in the physical properties of salicylic acid, as exemplified by a reduction in crystallinity, a lower and broader melting event, and a doubling of solubility.