Novel Glutaric Acid Cocrystal Formation via Cogrinding and Solution Crystallization

Abstract

An efficient and reliable approach to discover new pharmaceutical cocrystals in the early development stage is proposed and used to develop cocrystals of piracetam with some aliphatic diacids. A 1:1 cocrystal of piracetam and glutaric acid was screened by a mechanochemical method and identified by powder X‐ray diffraction and differential scanning calorimetry. Followed by solution crystallization, this cocrystal was reproduced. To better understand the mechanism of cocrystal formation in solution crystallization, process analytical technologies including focused beam reflectance measurement, attenuated total reflectance‐Fourier transform infrared, and particle vision measurement were applied to investigate the cocrystallization process of piracetam with glutaric acid. The mechanism of cocrystal formation during solution‐mediated phase transformation is discussed in detail.

PAT-based design of agrochemical co-crystallization processes: A case-study for the selective crystallization of 1:1 and 3:2 co-crystals of p-toluenesulfonamide/triphenylphosphine oxide

“…Co-crystallization can be an effective crystal engineering approach for modifying the crystal structure and properties of an active ingredient [8], [9]. However, many of the current methods used to isolate co-crystal forms such as neat and liquid assisted grinding [10], [11], slurry conversion [12], [13], supercritical fluid enhanced atomization [14], and evaporative co-crystallization [13], [15], [16] cannot be scaled to industrial production capacity. Cooling crystallization is perhaps the most viable route to scale-up, yet there are only a few studies that have explored this method to isolate co-crystals [17]- [19].…”

Extensive Analyses on Expanding the Scope of Acid–Aminopyrimidine Synthons for the Design of Molecular Solids

“…In all the synthesized products of 4-halobenzoic acids and 2-AP, both CO and OH peaks shifted to higher frequencies, while CO peaks shifted to lower frequency. Moreover, there was an absence of the symmetric carboxylate CO stretching band (around 1377 cm –1 ) in all the synthesized products that indicated the presence of hydrogen bonding, rather than proton transfer, leading to the formation of cocrystals. , …”

“…Moreover, there was an absence of the symmetric carboxylate CO stretching band (around 1377 cm −1 ) in all the synthesized products that indicated the presence of hydrogen bonding, rather than proton transfer, leading to the formation of cocrystals. 68,69 PXRD Analyses. PXRD is a popular method of estimating the crystallinity in starting materials and their ground mixture.…”

Application of Multivariate Adaptive Regression Splines (MARSplines) Methodology for Screening of Dicarboxylic Acid Cocrystal Using 1D and 2D Molecular Descriptors

“…The cocrystallization phenomenon can be quite tricky, since it not only depends on the thermodynamic aspects, but kinetic agents can also be crucial . A number of different supramolecular synthesis methods were developed including various solvent evaporation techniques, − antisolvent, − slurry, , melting, or mechanochemical approaches. ,− In the experimental part of this paper, the latter method was applied.…”