Multicomponent Materials to Improve Solubility: Eutectics of Drug Aminoglutethimide

Here, we report the synthesis and experimental characterization of three drug-drug eutectic mixtures of drug aminoglutethimide (AMG) with caffeine (CAF), nicotinamide (NIC) and ethenzamide (ZMD). The eutectic mixtures i.e., AMG-CAF (1:0.4, molar ratio), AMG-NIC (1:1.9, molar ratio) and AMG-ZMD (1:1.4, molar ratio) demonstrate significant melting point depressions ranging from 99.2 to 127.2 °C compared to the melting point of the drug AMG (151 °C) and also show moderately higher aqueous solubilities than that of the AMG. The results presented include the determination of the binary melt phase diagrams and accompanying analytical characterization via X-ray powder diffraction, FT-IR spectroscopy and scanning electron microscopy.

Thermal Behavior of the Nimesulide-Salicylic Acid Eutectic Mixtures Prepared by Mechanosynthesis and Recrystallization

Nimesulide, salicylic acid and their binary mixtures were studied by differential scanning calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The study of such systems is a promising and viable approach for solving the problem of poor solubility of materials in general and drug systems in particular. All areas of human activity are inextricably linked to materials, and thus, the study presented in the paper and not reported in the literature is very important and provides useful data for those working in various fields. The eutectic mixtures were obtained by mechanosynthesis and by recrystallization from ethanol over the entire 0–1 range of molar fractions. For both situations at the molar fraction of nimesulide 0.5, the mixture has a eutectic that suggests an increase in solubility at this composition. The interactions that take place between the components were determined with the help of the excess thermodynamic functions (GE, SE, µE), which highlight the deviation from the ideality of the considered binary systems.

Eutectic Formation of Naproxen with Some Dicarboxylic Acids

Eutectic formation with additives is one of the established methods to improve the dissolution behaviors of active pharmaceutic ingredients (APIs). The improvement is mainly due to the increase in the surface area for dissolution, which originates from the finely divided micro-domains generated through the phase separation of the miscible liquid components upon solidification. The present study is to identify eutectic-forming additives for naproxen (NPX), a class II API of the biopharmaceutical classification system. A particular aim was to develop a eutectic mixture with NPX at least over 20 wt%, a minimum to be practical for oral delivery. Screening based on the proximity of the solubility parameter values identified dicarboxylic acids (succinic acid, glutaric acid, and suberic acid) as desirable additives for NPX. Binary melting diagrams were constructed to confirm the eutectic compositions, and the eutectic mixture with suberic acid (NPX 55 wt%) was further investigated. The dissolution (at pH 5.0) of the melt crystallized eutectics was enhanced compared to the simple physical mixture of the same compositions and neat NPX, which was attributed to the microscopically observed lamellar structures. The current study should support the systematic investigations of API eutectic mixtures by selecting appropriate eutectic-forming additives.

Structural and Dynamic Properties of Hydrophobic Eutectic Solvents Based on Menthol and Fatty Acids: a Molecular Dynamics Simulation Study

The structural and dynamical properties of the binary mixture of Menthol (MEN) and Fatty acids (FAs) were investigated using molecular dynamics simulations. We focused on the relationship between the structural and dynamical properties of the eutectic mixtures of MEN and FAs with different molar percentages of FAs. Structural properties of the eutectic mixtures were characterized by calculating the combined distribution functions(CDFs), the radial distribution functions (RDFs), and the angular distribution functions (ADFs), and the Hydrogen bonding network between species and Spatial distribution functions (SDF). Further interaction between menthol and Caprylic acid molecules was confirmed by the results of these analyzes. Also, the transport properties of the mixtures were investigated by using the mean square displacement (MSD) of the centers of mass of the species, self-diffusion coefficients and vector reorientation dynamics (VRD) of bonds. The simulation results indicated that intermolecular interactions have a significant effect on the dynamic properties of species.

Multicomponent Materials to Improve Solubility: Eutectics of Drug Aminoglutethimide

Here, we report the synthesis and experimental characterization of three drug-drug eutectic mixtures of drug aminoglutethimide (AMG) with caffeine (CAF), nicotinamide (NIC) and ethenzamide (ZMD). The eutectic mixtures (AMG-CAF, AMG-NIC and AMG-ZMD) demonstrate significant melting point depressions ranging from 99.2 to 127.2 °C compared to the melting point of the drug AMG (151°C) and also show significantly higher aqueous solubilities than that of the AMG. The results presented include the determination of the binary melt phase diagrams and accompanying analytical characterization via X-ray powder diffraction, FT-IR spectroscopy and Scanning electron microscopy.

Choline Chloride-Based DES as Solvents/Catalysts/Chemical Donors in Pharmaceutical Synthesis

DES are mixtures of two or more compounds, able to form liquids upon mixing, with lower freezing points when compared to the individual constituents (eutectic mixtures). This attitude is due to the specific hydrogen-bond interactions network between the components of the mixture. A notable characteristic of DES is the possibility to develop tailor-made mixtures by changing the components ratios or a limited water dilution, for special applications, making them attractive for pharmaceutical purposes. In this review, we focused our attention on application of ChCl-based DES in the synthesis of pharmaceutical compounds. In this context, these eutectic mixtures can be used as solvents, solvents/catalysts, or as chemical donors and we explored some representative examples in recent literature of such applications.