Mechanism of Caking in 2,4-D Technical-Grade Crystals under the Influence of Impurities and a Predictive Model for Anti-Caking

Abstract

Existing caking models for soluble crystalline powders mainly describe the effects of particle size and humidity cycling, but the influence of internal impurities remains insufficiently quantified. Here, an impurity-inclusive framework was developed to predict the caking of 2,4-dichlorophenoxyacetic acid (2,4-D) technical crystals under humidity cycling. Three inherent impurities, 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenoxyacetic acid, and methyl 2,4-dichlorophenoxyacetate, were screened by dynamic vapor sorption (DVS) at 25 °C, and pure 2,4-DCP was additionally measured as a pure-component control. 2,4-DCP was identified as the key caking-relevant impurity and increased the apparent aqueous solubility of 2,4-D by more than fourfold. The pure-component DVS comparison further indicates that intrinsic moisture sorption by 2,4-DCP may additionally contribute to the moisture response, although this contribution is not independently parameterized in the present model. Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance (¹H NMR) analyses showed no detectable evidence of new covalent species during humidity cycling. The impurity-inclusive model was derived from crystal-bridge growth theory by explicitly introducing impurity concentration through an apparent-solubility correction. Validation under 48 experimental conditions gave an average relative deviation below 15%. For subsequent validation and prediction after model calibration, the estimated evaluation time was reduced by 87.9%, while the number of required experimental evaluations was substantially reduced relative to full empirical testing. An anti-caking design map indicates that maintaining 2,4-DCP below 1%, D₁₀ at or above approximately 200 μm, and the maximum relative humidity at or below approximately 60% can extend the predicted critical caking time beyond a 28-day engineering benchmark.