A crystalline radical cation derived from Thiele’s hydrocarbon with redox range beyond 1 V

Thiele’s hydrocarbon occupies a central role as an open-shell platform for new organic materials, however little is known about its redox behaviour. While recent synthetic approaches involving symmetrical carbene substitution of the CPh2 termini yield isolable neutral/dicationic analogues, the intervening radical cations are much more difficult to isolate, due to narrow compatible redox ranges (typically < 0.25 V). Here we show that a hybrid BN/carbene approach allows access to an unsymmetrical analogue of Thiele’s hydrocarbon 1, and that this strategy confers markedly enhanced stability on the radical cation. 1•+ is stable across an exceptionally wide redox range (> 1 V), permitting its isolation in crystalline form. Further single-electron oxidation affords borenium dication 12+, thereby establishing an organoboron redox system fully characterized in all three redox states. We perceive that this strategy can be extended to other transient organic radicals to widen their redox stability window and facilitate their isolation.

The Lactobacillus brevis Prebiotic Pure Exo polysaccharide and its Nano crystalline Characterization, anti-colon cancer and cytotoxicity

The present work established that the exopolysaccharide taken from Lactobacillus brevis and its Nano crystalline form are very efficient as an anti-colon cancer. The produced exopolysaccharide and its Nano crystalline were preliminarily conformed by UV spectroscopy, FTIR spectroscopy and TEM. The UV analysis revealed the peak at 258 nm which corresponds to exopolysaccharide and shifted to 270 for Nano crystalline. The uniform spherical shape and size was detected by TEM. The exopolysaccharide and nano prebiotic exopolysaccharide were evaluated for its cytotoxicity on CACO2 and WI-38 was tested by MTT assay. The result indicated decrease in cell viability. The present study highlighted the possibility of utilizing exopolysaccharide and its Nano crystalline form from Lactobacillus brevis for human applications as it enhanced anti-colon cancer.

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

The amorphous form of a drug usually exhibits higher solubility, faster dissolution rate, and improved oral bioavailability in comparison to its crystalline forms. However, the amorphous forms are thermodynamically unstable and tend to transform into a more stable crystalline form, thus losing their advantages. In order to investigate and suppress the crystallization, it is vital to closely monitor the drug solids during the preparation, storage, and application processes. A list of advanced techniques—including optical microscopy, surface grating decay, solid-state nuclear magnetic resonance, broadband dielectric spectroscopy—have been applied to characterize the physicochemical properties of amorphous pharmaceutical solids, to provide in-depth understanding on the crystallization mechanism. This review briefly summarizes these characterization techniques and highlights their recent advances, so as to provide an up-to-date reference to the available tools in the development of amorphous drugs.

ISOTHERM OF SOLUBILITY MANGANESE SULFATE - MONOETHANOLAMINE - WATER AT 25 ° C

Solubility in the ternary system manganese sulfate - monoethanolamine - water at 25°C was studied by isothermal method. The equilibrium in the system was controlled by liquid phase analysis. True equilibrium in the system was established within 7 hours. The new compound was isolated in crystalline form and identified by the methods of chemical, graphic, X-ray and thermal analyses. It was found that the new compound is a crystalline substance with an individual set of interplanar distances and line intensities. The formation of the new compound NH2C2H4ON-MnSO4-3H2O which was identified by the methods of chemical, graphic and X-ray analyses has been established. Preliminary agrochemical tests of aqueous solution of the new compound showed its positive properties as a stimulant.

DEVELOPMENT AND EVALUATION OF BICOMPONENT COCRYSTALS OF ACECLOFENAC FOR EFFICIENT DRUG DELIVERY WITH ENHANCED SOLUBILITY AND IMPROVED DISSOLUTION

This research work was intended to improve the solubility and dissolution of aceclofenac by the development of bicomponent cocrystals. Bicomponent cocrystals of aceclofenac were prepared with ten different cocrystal formers (CCF) by neat grinding techniques. Solubility analysis of cocrystals showed that aceclofenac-salicylic acid cocrystals have comparatively better solubility than the other cocrystals. The solubility of pure aceclofenac (309.23 µg/mL) was found to be improved by seven folds (2424.61 µg/mL) due to the formation of bicomponent crystalline form with salicylic acid. In vitro dissolution also revealed that the immediate release tablet of aceclofenac showed a release of 58.87±1.39 %, while aceclofenacsalicylic acid cocrystal tablet showed drug release of 92.65±1.21 % after 60 minutes. Results of Differential Scanning Colorimetry (DSC), Powdered X-Ray Diffraction (PXRD) and Raman spectroscopic analysis also justified the formation of the novel crystalline form. The developed bicomponent cocrystals of aceclofenac improved the solubility and dissolution of aceclofenac to a significant extent.

Amorphous Form of Carvedilol Phosphate—The Case of Divergent Properties

The amorphous form of carvedilol phosphate (CVD) was obtained as a result of grinding. The identity of the obtained amorphous form was confirmed by powder X-ray diffraction (PXRD), different scanning calorimetry (DSC), and FT-IR spectroscopy. The process was optimized in order to obtain the appropriate efficiency and time. The crystalline form of CVD was used as the reference standard. Solid dispersions of crystalline and amorphous CVD forms with hydrophilic polymers (hydroxypropyl-β-cyclodextrin, Pluronic® F-127, and Soluplus®) were obtained. Their solubility at pH 1.2 and 6.8 was carried out, as well as their permeation through a model system of biological membranes suitable for the gastrointestinal tract (PAMPA-GIT) was established. The influence of selected polymers on CVD properties was defined for the amorphous form regarding the crystalline form of CVD. As a result of grinding (four milling cycles lasting 15 min with 5 min breaks), amorphous CVD was obtained. Its presence was confirmed by the “halo effect” on the diffraction patterns, the disappearance of the peak at 160.5 °C in the thermograms, and the changes in position/disappearance of many characteristic bands on the FT-IR spectra. As a result of changes in the CVD structure, its lower solubility at pH 1.2 and pH 6.8 was noted. While the amorphous dispersions of CVD, especially with Pluronic® F-127, achieved better solubility than combinations of crystalline forms with excipients. Using the PAMPA-GIT model, amorphous CVD was assessed as high permeable (Papp > 1 × 10−6 cm/s), similarly with its amorphous dispersions with excipients (hydroxypropyl-β-cyclodextrin, Pluronic® F-127, and Soluplus®), although in their cases, the values of apparent constants permeability were decreased.

Structural reasons for the formation of multicomponent products and the influence of high pressure

(S)-(−)-1-Phenylethanaminium 4-(2,4,6-triisopropylbenzoyl)benzoate (S-PEATPBB) undergoes a photochemical reaction in its crystalline form upon UV irradiation and forms three different products: the first product is the result of a Yang cyclization with the participation of the δ-H atom of o-isopropyl (product D) and the second and third products are obtained via a Norrish–Yang reaction with the involvement of the γ-H atom of 2-isopropyl (product P) and 6-isopropyl (product Z). These products are formed in different proportions (D > P >> Z). The path and kinetics of the reaction were monitored step-by-step using crystallographic methods, both under ambient and high-pressure conditions. The reactivity of S-PEATPBB depends strongly on the geometry of the reaction centre and the volume of the reaction cavity. Due to the geometrical preferences making the cyclization reaction easier to proceed, product D dominates over the other products, while the formation of product Z becomes difficult or almost impossible at high pressure. The reaction proceeds with an increase of the unit-cell volume, which, suppressed by high pressure, results in a significant decrease of the reaction rate. The crystal lattice of S-PEATPBB shows high elasticity. The quality of the partially reacted crystal remains the same after decompression from 0.75 GPa to 0.1 MPa.

Combinations of Freeze-Dried Amorphous Vardenafil Hydrochloride with Saccharides as A Way to Enhance Dissolution Rate and Permeability

To improve physicochemical properties of vardenafil hydrochloride (VAR), its amorphous form and combinations with excipients—hydroxypropyl methylcellulose (HPMC) and β-cyclodextrin (β-CD)—were prepared. The impact of the modification on physicochemical properties was estimated by comparing amorphous mixtures of VAR to their crystalline form. The amorphous form of VAR was obtained as a result of the freeze-drying process. Confirmation of the identity of the amorphous dispersion of VAR was obtained through the use of comprehensive analysis techniques—X-ray powder diffraction (PXRD) and differential scanning calorimetry (DSC), supported by FT-IR (Fourier-transform infrared spectroscopy) coupled with density functional theory (DFT) calculations. The amorphous mixtures of VAR increased its apparent solubility compared to the crystalline form. Moreover, a nearly 1.3-fold increase of amorphous VAR permeability through membranes simulating gastrointestinal epithelium as a consequence of the changes of apparent solubility (Papp crystalline VAR = 6.83 × 10−6 cm/s vs. Papp amorphous VAR = 8.75 × 10−6 cm/s) was observed, especially for its combinations with β-CD in the ratio of 1:5—more than 1.5-fold increase (Papp amorphous VAR = 8.75 × 10−6 cm/s vs. Papp amorphous VAR:β-CD 1:5 = 13.43 × 10−6 cm/s). The stability of the amorphous VAR was confirmed for 7 months. The HPMC and β-CD are effective modifiers of its apparent solubility and permeation through membranes simulating gastrointestinal epithelium, suggesting a possibility of a stronger pharmacological effect.