https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/ejoc.201700961

Mechanochemistry for Organic Chemists: An Update

Mechanochemistry deals with reactions induced by the input of mechanical energy – for example by impacts within a vibratory ball mill. The technique has a long history with significant contributions from Ostwald, Carey Lea and, notably, Faraday. Mechanochemistry has subsequently seen application in a variety of areas of materials science including mechanical alloying in metallurgy, the synthesis of complex organic molecules and, more recently, the discovery and development of new solid forms of active pharmaceutical ingredients. This paper overviews the broad areas of application of mechanochemistry, some key features which make it a particularly attractive approach to materials synthesis and some mechanistic aspects highlighted within the literature. A significant part, however, will focus on recent applications in the area of pharmaceuticals and its important role in exploring the rich variety of solid forms available for small, drug-like, molecules.

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Introductory Lecture: Mechanochemistry, a versatile synthesis strategy for new materials

The multiparameter model comprising 1D and 2D QSPR/QSAR descriptors was proposed and validated for phenolic acid binary systems. This approach is based on the optimization of regression coefficients for maximization of the percentage of true positives in the pool of systems comprising either simple binary eutectics or cocrystals. The training set consisted of 58 eutectics and 168 cocrystals. The solid dispersions collection used for model generation comprised literature data enriched with our new experimental results. From all 1445 descriptors computable in PaDEL, only 13 orthogonal descriptors with the highest predicting power were taken into account. The analysis revealed the importance of the parameters characterizing atom types (naaN, SHsOH, SsssN, nHeteroRing, maxHBint6, C1SP2), autocorrelation functions (ATSC1i, AATSC1v, MATS8m, GATS1i), and also other molecule structure measures (WTPT-5, MLFER_A, MDEN-22). The proposed approach is very simple and requires only information about the structure encode...

Distinguishing Cocrystals from Simple Eutectic Mixtures: Phenolic Acids as Potential Pharmaceutical Coformers

Spectroscopic investigation on cocrystal formation between adenine and fumaric acid based on infrared and Raman techniques.

Raman and terahertz spectroscopical investigation of cocrystal formation process of piracetam and 3-hydroxybenzoic acid

Using terahertz time-domain spectroscopical technique to monitor cocrystal formation between piracetam and 2,5-dihydroxybenzoic acid

Pharmaceutical cocrystal can improve physical and chemical properties of active pharmaceutical ingredient (API), meanwhile this feature has shown great potential in improving the pharmaceutical's properties and characteristics. In this study, cocrystal formation between piracetam and 3-hydroxybenzoic acid (3HBA) using grinding method has been characterized by Fourier transform infrared (FTIR), Raman and terahertz (THz) spectroscopical techniques. The vibrational modes of different motions are obtained by the assignment of the peaks in the spectra of the starting materials and the cocrystal components. FTIR, Raman and THz spectroscopical results show that the vibrational modes of the cocrystal are different from those of the starting materials. In addition, the dynamic process of the above cocrystal formation is investigated in-depth with Raman and THz spec- tra. Piracetam-3HBA cocrystal is formed pretty fast in first several minutes, and then the formation rate becomes slow. After 35 minutes, such formation process has been completed. The results offer the theoretical benchmark and unique means for real-time monitoring pharmaceutical cocrystal formation and also the corresponding quantitative analysis in the pharmaceutical field.

Yi Xia

Papers

Using terahertz time-domain spectroscopical technique to monitor cocrystal formation between piracetam and 2,5-dihydroxybenzoic acid

Raman and terahertz spectroscopical investigation of cocrystal formation process of piracetam and 3-hydroxybenzoic acid

[Spectral Analysis about the Pharmaceutical Cocrystal Formation of Piracetam and 3-Hydroxybenzoic Acid].