Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol

A thorough, systematic study into the effect that structurally related impurities have on both the process and product quality during the crystallization of an active pharmaceutical ingredient is presented. The presence of acetanilide and metacetamol influences the crystallization and product quality of paracetamol. Where high concentrations of either impurity were present in the crystallization feed, product recovery decreased by up to 15%. Acetanilide is included in the final product through adsorption onto the particle surface in concentrations up to 0.79 mol%, which can be reduced to acceptable levels through product reslurrying. The presence of metacetamol results in much higher concentrations—up to 6.78 mol% in the final product, of which approximately 1 mol% is incorporated into the crystal lattice, resulting in the perturbation of the unit-cell dimensions. The incidental crystallization and subsequent isolation of metastable Form II paracetamol increased product purity in the presence of a low metacetamol concentration. This metastable product converts to stable paracetamol Form I through reslurrying, offering an efficient metacetamol impurity rejection route. The morphology of the product is modified consistently by both impurities. An elongation of the normal prismatic shape is observed, which in the extreme case of high metacetamol contamination results in the isolation of fine, fragile needles. This problematic morphology is also improved by a reslurrying of the crystallization product to give a more equilateral shape. This systematic study of the influence of acetanilide and metacetamol on the crystallization of paracetamol builds a well-rounded picture of the concomitant impact of impurities on the principal quality attributes of a crystallization product.

Interfacial Microstructure in W/2024Al Composite and Inhibition of W-Al Direct Reaction by CeO2 Doping: Formation and Crystallization of Al-Ce-Cu-W Amorphous Layers

In this work, interfacial microstructure in W/2024Al composite and inhibition of the W-Al direct reaction by CeO2 doping were investigated. The composites were prepared through powder sintering, and after preparation the composites were treated by annealing at 823 K. For the prepared W/2024Al composite, a multi-phase thin layer composed of WAl12 and WAl5 compounds were formed at the interface due to the W-Al direct reaction. While doping CeO2 in the composite, Al-Ce-Cu-W amorphous substituting of W-Al compounds were formed at the interfacial reaction layer. In an annealed state, the composite with CeO2 doping shows a significant inhibitory effect on W-Al compounds, which was attributed to the crystallized layer that evolved from Al-Ce-Cu-W amorphous as an interfacial obstacle. The crystallization product for Al-Ce-Cu-W amorphous layer was identified as bcc-structure Al-Ce-Cu-W phase without any binary/ternary Ce-containing phases. Therefore, by doping CeO2 in W/2024Al composite, W-Al direct reaction was markedly inhibited during both preparation and annealing.

Organic matrix-induced formation of a discrete cyclic [Cl2(H2O)2]2− cluster

Reaction of 6-NH2-Py-2-NHC(S)NHP(S)(OiPr)2 with DMFA·2HCl leads to the co-crystallization product of 2,6-di(4H-1,2,4-triazol-4-yl)pyridine and 2,6-diaminopyridinium chloride monohydrate (1) and N-(diisopropoxythiophosphoryl)-N′-(6-(4H-1,2,4-triazol-4-yl))pyridin-2-ylthiocarbamide (2).

Synthesis and Antimicrobial Activity of Silver Citrate Complexes

Formation of silver citrate/citric acid complexed solutions was investigated. Although, silver citrate is minimally soluble in water, it can successfully be dissolved in citric acid solutions. The maximum concentration of Ag(I) in solution is estimated at 23 to 25 g/L if the concentration of citric acid is at least 4 mol/L or higher. The dissolution of silver citrate in citric acid solutions was attributed to the formation of silver citrate complexes of a general formula[Ag3(C6H5O7)n+1]3n−. The silver citrate/citric acid solutions, containing more than about 13 g/LAg+ion, have exhibited a decrease in Ag(I) concentration in solution over time, due to crystallization. The crystallization product was attributed to the formation of[Ag3C6H5O7]x⋅nH2O. Importantly, the diluted silver citrate/citric acid complexed solutions have exhibited very strong bacteriostatic and bactericidal activities.

Effect of the Supercooled Liquid Region on Al85Ni7Gd8 Metallic Glass Crystallization Products

ABSTRACTThe effect of the supercooled liquid region on the primary crystallization of Al85Ni7Gd8 metallic glass, which exhibits a clear glass transition before its primary crystallization, was evaluated systematically under different annealing conditions, including isothermal annealing at different temperatures and non-isothermal annealing employing different heating rates. It was found that isothermal annealing within the supercooled liquid region and non-isothermal annealing at small heating rates (≤ 5 °C/min) result in the co-precipitation of fcc-Al and Al compound(s). When isothermal annealing is done at temperatures where partial crystallization is involved, or non-isothermal annealing is carried out at a larger heating rate, the primary crystallization product is a single phase of fcc-Al. The effect of the supercooled liquid region on the crystallization product is discussed in detail.