Stabilizing L-Menthol by Cocrystallization: Supramolecular Cavities Succeeded in Retaining the Volatile Flavor

Abstract

L-menthol is one of the most important flavoring additives with abundant plant sources. The distinctive odor, cooling characteristic, and diversified biological activities attribute to its widespread application, especially on confections, oral-care commodities, over-the-counter drugs, and tobacco flavors. However, the manufacturing and storage of L-menthol face challenges due to its high volatility and low melting point. In this work, cocrystallization provides a new strategy to manage the stability problem of this important ingredient. Coformers of dietary sources were chosen based on a supramolecular synthon design, and six cocrystals of L-menthol were synthesized by either a solventmediated or solvent-free approach. These new solid forms could significantly increase the melting point and reduce the vapor pressure up to 1/45 of the pure L-menthol. Moreover, cocrystals present a high retention rate under storage conditions. The superior stability can be ascribed to diversified supramolecular cavities assembled by coformers, to which L-menthol molecules are restricted by hydrogen bonds.

Control of Liquid–Liquid Phase Separation, Nucleation, and Growth of L‐Menthol Single Crystals from Water–Ethanol Solvent Mixtures

“…For example, in order to increase the permeation of lopinavir in intestinal segments, the formation of cocrystal with L-menthol as a coformer is being carried out during the industrial process. [18][19][20][21] In this work, we examine LLPS during the crystallization of L-menthol in water at a solution preparation stage above ambient temperature. We carefully monitored the formation of oil droplets, followed by crystal nucleation and the generation of Lmenthol crystals.…”

Green materials with promising applications: cyclodextrin-based deep eutectic supramolecular polymers

“…79,80 This not only retains the enantiomeric recognition and encapsulation ability of CDs but also combines the solubilization characteristics of DESs, resulting in enhanced beneficial properties of the individual components. 81,82 Thus, SUPRADESs are applied extensively in the extraction, separation, and transport of compounds.…”

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

“…Chemical compounds may manifest in a multitude of solid-state forms, potentially leading to disparate intermolecular interactions that influence both the internal energy and the enthalpy along with the extent of disorder, impacting the entropy. − Consequently, these varying forms typically exhibit significant disparities in their physicochemical properties, encompassing characteristics like melting point, solubility, dissolution rate, chemical stability, and vapor pressure . At present, the strategic deployment of solid-state forms has gained widespread recognition across numerous disciplines, including pharmaceuticals, functional materials, and energetic materials …”

“…9−11 Consequently, these varying forms typically exhibit significant disparities in their physicochemical properties, encompassing characteristics like melting point, 12 solubility, 13 dissolution rate, 14 chemical stability, 15 and vapor pressure. 16 At present, the strategic deployment of solid-state forms has gained widespread recognition across numerous disciplines, including pharmaceuticals, 17 functional materials, 18 and energetic materials. 19 While agrochemical ingredients (AIs) have traditionally not been as comprehensively researched as active pharmaceutical ingredients (APIs), the organic solid state has begun to command escalating attention within contemporary agrochemical chemistry over the past decade.…”