Caking of L-histidine monohydrochloride monohydrate crystals induced due to trace moisture sorption without...

L-Histidine monohydrochloride monohydrate (HIS HCl H₂O) is a commercially produced crystalline powder used in the food, pharmaceutical, and feed industries. During the commercial distribution and storage of HIS HCl H₂O, customer complaints have arisen due to undesired caking. However, the caking mechanism and potential solutions for HIS HCl H₂O crystals have not been thoroughly investigated. In this study, we experimentally measured moisture sorption and the degree of caking at various temperatures and relative humidity (RH) conditions to investigate the caking mechanism of HIS HCl H₂O crystals. It was found that caking of HIS HCl H₂O crystals occurs at a temperature of 70 °C and a RH of 80 %, even with a moisture content of less than 0.1 %. This caking occurred without evaporative crystallization from moisture desorption. During the caking of HIS HCl H₂O crystals, fine crystals were removed, and intermediate-sized crystals grew, with increasing mean particle size from 435.7 to 475.1 μm. However, no remarkable polymorphic changes were observed. The caking was more severe for the sample with smaller crystal size. At a temperature of 70 °C and a RH of 80 %, the lump production ratio and breakable ratio of crystals smaller than 125 μm were 99.8 % and 24.9 %, respectively. However, crystals in the size range of 500-1000 μm did not show any lump formation. Based on these findings, decreasing cooling rate during crystallization process was applied as an effective strategy to prevent lump formation by increasing crystal size during the commercial manufacturing process of HIS HCl H₂O.