Genuine antiplasticizing effect of water on a glass-former drug

Abstract

Water is the most important plasticizer of biological and organic hydrophilic materials, which generally exhibit enhanced mechanical softness and molecular mobility upon hydration. The enhancement of the molecular dynamics upon mixing with water, which in glass-forming systems implies a lower glass transition temperature (T g), is considered a universal result of hydration. In fact, even in the cases where hydration or humidification of an organic glass-forming sample result in stiffer mechanical properties, the molecular mobility of the sample almost always increases with increasing water content, and its T g decreases correspondingly. Here, we present an experimental report of a genuine antiplasticizing effect of water on the molecular dynamics of a small-molecule glass former. In detail, we show that addition of water to prilocaine, an active pharmaceutical ingredient, has the same effect as that of an applied pressure, namely, a decrease in mobility and an increase of T g. We assign the antiplasticizing effect to the formation of prilocaine-H 2 O dimers or complexes with enhanced hydrogen bonding interactions.

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

“…The red traces correspond to pure PLC, the blue traces are the hydrated PLC samples (as mentioned previously, hereafter the term hydrated PLC stands for the equilibrium liquid L 1 , which corresponds to the solubility limit of water in prilocaine). Gray dotted lines are the tangents used to obtain the onset glass transition temperatures, T g , which are found to be 221.4 ± 0.5 K and 225.3 ± 0.5 K for the pure and hydrated bulk samples, respectively, consistent with our previous results 16 . This confirms the antiplasticizing effect of water on bulk prilocaine, since an increase of about 4 K is produced upon hydration.…”

“…We carry out Broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC) measurements on pure and hydrated prilocaine, confined in molecular sieves of 0.5 and 1 nm pore size. We find that confinement leads to substantial lowering of the glass transition temperature, and that the antiplasticizing effect of water on the prilocaine matrix is systematically observed also in the confined system as in the bulk 16 . The current results point to the formation of PLC-water molecular aggregates as the cause of the observed increase of T g upon hydration.…”

“…A heating/cooling rate of 8 K/min was employed. All samples were melted inside the DSC by keeping them at 313.5 K for 5 minutes and subsequently cooled to 203.15 K followed by an annealing to enhance the visibility of the calorimetric signal of the glass transition, as done in our previous work 16 . The annealing temperature was chosen as 215.2 K for bulk and 0.5 nm samples (as done in Ref.…”

“…The annealing temperature was chosen as 215.2 K for bulk and 0.5 nm samples (as done in Ref. 16 ), and 203.5 K for 1 nm samples, chosen so as to perform the annealing about 5 K below T g . The details of the latter protocol can be found in the supplementary material.…”

“…The two phases are thermodynamically stable at ambient conditions 20 . The antiplasticizing effect of water in prilocaine leads to a significant increase of T g and of the structural relaxation time at fixed temperature, both of which increase with increasing water content, reaching a maximum at the saturation concentration, corresponding to the L 1 phase, which we will refer to as "hydrated prilocaine" in the following 16 . The characterization of solutions under nanometric confinement, e.g.…”