(727h) Cryogenic Crystallization Vs Conventional Crystallisation

We explore in the work and establish the novel concept of cryo-crystallization—the formation of nuclei around transiently lived cold-spots in warm supersaturated liquid that surrounds them but does not nucleate on its own. Each super-cold drop of dispersed phase helps create a super-cold zone around it with high degree of supersaturation favoring nucleation. Once the nuclei born reach the surrounding warm and supersaturated liquid, the crystals grow at high growth rates prevailing at high temperatures. The cold spots introduced by dispersing ultra-cold fluid rapidly eventually warm up and cease to play any role, but in their short low temperature life, they generate nuclei.

We have chosen mannitol-water system for this purpose as it offers a large metastable region in its phase diagram. Cryogens such as liquid nitrogen (LIN)/cold liquid hexane are dispersed directly into the mother liquor to serve as transiently lived cold spots.

The decoupling of nucleation and growth mechanism is tested by comparing conventional industrial crystallization with cryogenic crystallization (driven by mixture of liquid nitrogen and its vapors and cold hexane) in a 1-L laboratory-scale batch reactor. Cryogenic crystallization demonstrates a superior performance. The cryogenic systems induce nucleation at comparatively higher bulk temperature than that required for primary nucleation to occur. The particles obtained with cryogenic crystallization are much smaller in mean size with narrower size distribution, and reach a given yield of crystals in less process time. Both cryogenic and conventional methods produced needle-like β polymorph crystals with varied aspect ratio (from stunted to long needles). The spread in the width of needle like particles demonstrated that nucleation for conventional crystallization occurs over a prolonged time while in the case of cryogenic crystallization it is intense and short-lived. The average ratio of length to width is needles is about ten but only about seven for seeded crstallization. A set of carefully designed experiments unraveled negligible role of nucleation on the interfaces between immiscible fluids. The experimental study provides the first proof-of-concept for cryo-crystallization on laboratory scale.

A nucleation-growth model for a well-mixed vessel to gain insights into the measurements---nearly constant rate of decrease in solute concentration with time. To begin, the model represents the growth of needle-shaped particles of different sizes by the growth of an average-sized spherical particle. The screening methods help identify the constitutive relations that fit the measurements for the unseeded mode of crystallization. The diffusion-controlled growth of particles is too fast to capture the dynamics of the process completion. The surface process-controlled particle growth can fit the dynamics, but it predicts accelerated solute consumption with time because of an increase in the surface area of particles; however, the experiments show near-constant solute consumption. Incorporating particle breakup in the model further increases the surface area for growth and accelerates the solute consumption at an earlier time. The model suggests that the accelerated solute consumption due to the increase in surface area needs to be counter-acted through the sensitive dependence of growth rate on supersaturation, which decreases with time.