Tuning molecular dynamics by hydration and confinement: antiplasticizing effect of water in hydrated prilocaine nanoclusters

Abstract

Antiplasticizing effect of hydration vs. plasticizing effect of nanoconfinement in a molecular glass former.

Influence of Water on Amorphous Lidocaine

“…Figure 4A shows the influence of water on the T g of PRL and the T g of the co-amorphous system. The T g of PRL increased upon hydration, which was consistent with a previous study by Ruiz et al (2019) that showed that water had an antiplasticizing effect on PRL. 8 The saturated water-to-drug ratio for hydrated PRL was X Hd 2 O = 50%, corresponding to the formation of a PRL dimer held together by a water molecule.…”

“…The T g of PRL increased upon hydration, which was consistent with a previous study by Ruiz et al (2019) that showed that water had an antiplasticizing effect on PRL. 8 The saturated water-to-drug ratio for hydrated PRL was X Hd 2 O = 50%, corresponding to the formation of a PRL dimer held together by a water molecule. 7 Interestingly, below the saturated water ratio, the T g of PRL varied linearly with X Hd 2 O (Figure 4A, yellow line).…”

“…As a result, the glass-transition temperature ( T g ), which is assumed to generally link to physical stability, will have a tendency to decrease upon addition of water . However, some recent studies exhibit that water actually has an anti-plasticizing effect on the drug prilocaine (PRL). , PRL is an amide-type local anesthetic, which shows maximum hydration in a miscible liquid phase at a water/PRL molar ratio of X H 2 O = 50% . Further addition of water will separate the PRL–water system into two immiscible thermodynamically stable liquid phases: a water-saturated PRL liquid phase ( X H 2 O = 50%) and a water-rich liquid phase .…”

New State-Diagram of Aqueous Solutions Unveiling Ionic Hydration, Antiplasticization, and Structural Heterogeneities in LiTFSI–H2O

“…Another interesting property of the LiTFSI solution is a recently observed antiplasticizing effect of water, that is, an increase in the water content increases the glass transition temperature, T g , of this system. , Actually, the analogous behavior has already been observed in other aqueous solutions, such as those of butyltripropylammonium chloride (BuPr 3 NCl), n -propylene glycol monomethyl ethers (nPGMEs), prilocaine, , polyamide 6, and carbohydrate, respectively. Usually, the enhanced hydrogen-bonding interactions between hydration water and molecular hydrophilic groups, such as the hydroxyl end groups of nPGME ( n = 1–3), have been suggested to be the main cause of this abnormal water increasing T g behavior.…”

Glass transition, crystallization kinetics, and inter-conformer relaxation dynamics of amorphous mitotane and related compounds

“…Therefore, it is the nanoconfinement in micellar dispersions that is responsible for the kinetic metastability of the supercooled liquid phase of recently reported mitotane formulations (Haider et al, 2020). Recent studies of organic glass formers under geometrical confinement indicate that the structural relaxation is suppressed in nanoconfined liquids where molecules form only small clusters and only the Johari-Goldstein relaxation is present (Ngai et al, 2019(Ngai et al, , 2020Ruiz et al, 2019). The metastabilization of micellar mitotane at room temperature may therefore be favored by the suppression of the structural relaxation of mitotane in nanoscopic domains, where only the faster and less cooperative Johari-Goldstein and intramolecular relaxation processes may be active.…”