Mechanochemical Synthesis of Polymorphic Urea ⋅ Adipic Acid Cocrystal as a Sustained‐Release Nitrogen Source

Abstract

A 2 : 1 urea • adipic acid cocrystal was obtained in two polymorphic forms (Form I reported earlier, and Form II synthesized in this study) using mechanochemistry as well as solution crystallization. Lower solubility and leaching study showed the newly synthesized urea • adipic acid 2 : 1 cocrystal to be an efficient sustained-release nitrogen fertilizer compared to commercially available urea.

Opportunities and Challenges in Mechanochemical Cocrystallization toward Scaled-Up Pharmaceutical Manufacturing

“…In contrast, kinetic methods occur under nonequilibrium conditions centered on reaction duration and system energy, giving rise to a metastable form with higher free energy. Sublimation crystallization, supercritical fluid technology, and spray drying are exemplars classified under kinetic methods, whereas slurry sonication and slow evaporation are examples of thermodynamic methods. , Grinding is somewhat difficult to consider among either of the two categories, as examples are available in the literature that show the formation of both metastable (kinetic) − and thermodynamic polymorphs ,− during mechanochemical synthesis. Therefore, a thorough investigation of mechanochemical kinetics as well as various milling conditions is necessary in order to understand the outcome of the reaction and/or formation of product. ,− Douroumis et al and Karimi-Jafari et al independently discussed various available cocrystallization techniques as well as their inherent challenges in two separate reviews.…”

Pursuing Green and Efficient Agriculture from Molecular Assembly: A Review of Solid-State Forms on Agrochemicals

“…In addition, the cocrystallization of urea with the urease inhibitor catechol delivers an organic substance that can function as both a soil fertilizer and an effective urease inhibitor, not just as an inhibitor to reduce urea nitrogen loss but also as a material with enhanced hygroscopic stability. 192 In the pursuit of designing more urea cocrystals with superior controlled release properties, the theoretical screening method was employed due to the small molecular size, flexible conformation, and abundant hydrogen bond formation sites of urea. A set of five preferred synthons with which urea tends to engage was distilled based on comprehensive interaction maps (FIMs, Figure 12d) and the cocrystal structure data set of urea, as collated in the Cambridge Structural Database (CSD), depicted in Figure 12e.…”

“…(c) Urea release profile of urea–adipic acid form II, a mixture of forms I and II, and commercial urea. Reprinted with permission from ref . Copyright 2021 John Wiley and Sons.…”

Mechanochemistry as an emerging tool for the preparation of sustained release urea cocrystals as a nitrogen source

“…Very recently, Parakatawella et al reported 48 a urea·adipic acid cocrystal based on mechanochemistry as an alternative source of N. The selection of adipic acid as a coformer was due to its low solubility and non-toxic behavior. They explored the possibility of polymorphism and synthesized a thermodynamically stable cocrystal form (form II) that has better moisture stability, low solubility (∼77 mg per 1 mL; 96.8% reduction in solubility compared to pure urea) and sustained release property.…”