Changes in Physical Stability of Supercooled Etoricoxib after Compression

In the case of formulations with amorphous active pharmaceutical ingredients the risk of pressure-induced recrystallization should be carefully considered. We reported here that supercooled etoricoxib (ETB), which was found as a relatively stable system with low crystallization tendency at atmospheric pressure, crystallized quickly after compression. The observed strong pressure-dependence of the induction period suggests that during compression the first step of crystallization that is nucleation may be accelerated. To overcome the experimental challenge associated with studies at elevated temperatures and high pressures we applied broadband dielectric spectroscopy. Dielectric measurements gave us detailed insight into crystallization kinetics of ETB at varying (<i>T</i>, <i>p</i>) conditions corresponding to the supercooled liquid state of a drug. We found that pressure-induced recrystallization of supercooled ETB, constituting a serious impediment from a technological point of view, can be efficiently inhibited when amorphous solid dispersion containing ETB and polymer polyvinylpyrrolidone PVP (10% w/w) was prepared. Besides, we performed the comprehensive analysis of molecular dynamics of both systems at elevated pressure to address some fundamental issues related to the pressure sensitivity of their supercooled dynamics

Molecular Dynamics, Recrystallization Behavior, and Water Solubility of the Amorphous Anticancer Agent Bicalutamide and Its Polyvinylpyrrolidone Mixtures

In this paper, we investigated the molecular mobility and physical stability of amorphous bicalutamide, a poorly water-soluble drug widely used in prostate cancer treatment. Our broadband dielectric spectroscopy measurements and differential scanning calorimetry studies revealed that amorphous BIC is a moderately fragile material with a strong tendency to recrystallize from the amorphous state. However, mixing the drug with polymer polyvinylpyrrolidone results in a substantial improvement of physical stability attributed to the antiplasticizing effect governed by the polymer additive. Furthermore, IR study demonstrated the existence of specific interactions between the drug and excipient. We found out that preparation of bicalutamide–polyvinylpyrrolidone mixture in a 2–1 weight ratio completely hinder material recrystallization. Moreover, we determined the time-scale of structural relaxation in the glassy state for investigated materials. Because molecular mobility is considered an important factor governing crystallization behavior, such information was used to approximate the long-term physical stability of an amorphous drug and drug–polymer systems upon their storage at room temperature. Moreover, we found that such systems have distinctly higher water solubility and dissolution rate in comparison to the pure amorphous form, indicating the genuine formulation potential of the proposed approach

Revealing the Charge Transport Mechanism in Polymerized Ionic Liquids: Insight from High Pressure Conductivity Studies

Polymerized ionic liquids (polyILs), composed mostly of organic ions covalently bonded to the polymer backbone and free counterions, are considered as ideal electrolytes for various electrochemical devices, including fuel cells, supercapacitors, and batteries. Despite large structural diversity of these systems, all of them reveal a universal but poorly understood feature: a charge transport faster than the segmental dynamics. To address this issue, we studied three novel polymer electrolyte membranes for fuel cells as well as four single-ion conductors, including highly conductive siloxane-based polyIL. Our ambient and high pressure studies revealed fundamental differences in the conducting properties of the examined systems. We demonstrate that the proposed methodology is a powerful tool to identify the charge transport mechanism in polyILs in general and thereby contribute to unraveling the microscopic nature of the decoupling phenomenon in these materials