Intermolecular hydrogen transfer and solubility tuning in multi-component molecular crystals of the API piroxicam

Twelve multi-component molecular crystals of the active pharmaceutical ingredient (API) piroxicam (PX) are described contrasting those with basic N-heterocycles with those formed with strong haloanilic acids. The effect on the solubility of this API is discussed, with evidence of enhanced solubility in the multi-component crystals formed.</p

Tuning crystal morphology of succinic acid using a polymer additive

The effect of the triblock copolymer Pluronic P123 (PP123) on the growth of succinic acid crystals from aqueous solutions is reported at two batch process scales: 10 and 350 mL. The presence of small quantities of PP123 is shown to modify the crystal morphology from plate-like crystals to block-like crystals, in a fully reproducible manner. Increasing the quantity of polymer present, or the concentration of succinic acid used, produces needle-like crystals that are less favorable for processing. In-line process analytical tools (FBRM, PVM, and Raman) were implemented for the larger volume batch processes, allowing the crystallization to be monitored in real time. The effect of the polymer on the metastable zone width (MSZW) has also been determined in designing the crystallization experiments and is presented. In addition, the effect of the individual blocks of the copolymer, poly(ethylene glycol) and poly(propylene glycol), on the crystal morphology was examined, and these findings, together with face indexing and knowledge of the underlying crystal structure, have allowed a possible mechanism to be constructed for the interaction of the polymer with the crystal surface. This mechanism is supported by subsequent recrystallization experiments following washing of the block-like crystals with a nonpolar solvent

Design and Evaluation of a Mesoscale Segmented Flow Reactor (KRAIC)

The design and development of a mesoscale flow reactor is presented, together with initial performance evaluation. The custom-designed KRAIC (kinetically regulated automated input crystallizer) uses liquid-segmented flow to achieve plug flow and mixing throughout the reactor length while helping prevent encrustation issues experienced by other precipitation reactors and crystallizers. Evaluation of the reactor for production of solid-state particle products has been carried out using cooling crystallization of fast growing succinic acid to explore the potential of the KRAIC design to mediate blocking caused during the precipitation process. The segmented flow environment is successful in preventing encrustation during an unseeded 2 h cooling crystallization experiment

Design and Evaluation of a Mesoscale Segmented Flow Reactor (KRAIC)

The design and development of a mesoscale flow reactor is presented, together with initial performance evaluation. The custom-designed KRAIC (kinetically regulated automated input crystallizer) uses liquid-segmented flow to achieve plug flow and mixing throughout the reactor length while helping prevent encrustation issues experienced by other precipitation reactors and crystallizers. Evaluation of the reactor for production of solid-state particle products has been carried out using cooling crystallization of fast growing succinic acid to explore the potential of the KRAIC design to mediate blocking caused during the precipitation process. The segmented flow environment is successful in preventing encrustation during an unseeded 2 h cooling crystallization experiment