Crystallization processes solvent

Gas AntisolventRecrystallizations. A limitation to the RESS process can be the low solubihty in the supercritical fluid. This is especially evident in polymer—supercritical fluid systems. In a novel process, sometimes termed gas antisolvent (GAS), a compressed fluid such as CO2 can be rapidly added to a solution of a crystalline soHd dissolved in an organic solvent (114). Carbon dioxide and most organic solvents exhibit full miscibility, whereas in this case the soHd solutes had limited solubihty in CO2. Thus, CO2 acts as an antisolvent to precipitate soHd crystals. Using C02 s adjustable solvent strength, the particle size and size distribution of final crystals may be finely controlled. Examples of GAS studies include the formation of monodisperse particles (<1 fiva) of a difficult-to-comminute explosive (114) recrystallization of -carotene and acetaminophen (86) salt nucleation and growth in supercritical water (115) and a study of the molecular thermodynamics of the GAS crystallization process (21). 

Crystalline polyesters are highly important as adhesive raw materials. They are normally crystalline waxes and are highly symmetrical in nature, which can aid the crystallization process [26]. Poly(hexamethylene adipate) and poly(caprolactone), shown in Table 2, are only two of the many crystallizable backbones. Poly(ethylene adipate) and poly(letramethylene adipate) are also commonly used in urethane adhesives. The crystalline polyesters are used in curing hot melts, waterborne polyurethanes, thermoplastic polyurethanes, and solvent-borne urethane adhesives. The adipates are available mostly as diols. The poly(caprolactones) are available as diols and triols. 

That benzene hexachloride isomer mixture is then the raw material for lindane production. The production of lindane per se is not a chemical synthesis operation but a physical separation process. It is possible to influence the gamma isomer content of benzene hexachloride to an extent during the synthesis process. Basically, however, one is faced with the problem of separating a 99%-plus purity gamma isomer from a crude product containing perhaps 12 to 15% of the gamma isomer. The separation and concentration process is done by a carefully controlled solvent extraction and crystallization process. One such process is described by R.D. Donaldson et al. Another description of hexachlorocyclohexane isomer separation is given by R.H. Kimball. 

Figure 10-14. The SNIA BPD process for producing caprolactam (1) toluene oxidation reactor, (2) fractionator, (3) hydrogenation reactor (stirred autoclave), (4) multistage reactor (conversion to caprolactam), (5) water dilution, (6) crystallizer, (7) solvent extraction, (8) fractionator.

On the other hand, the crystallization process of diolefin compounds often plays a significant role in determining their topochemical behaviour, by changing their crystal structure or by forming solvent inclusion complexes. Furthermore, topochemical photoreactions of crystals with )8-type packing are accompanied by thermal processes under moderate control by the reacting crystal lattice (see p. 140). These factors seriously complicate the whole reaction scheme. 

Aseptic Crystallization and Dry Powder Filling. Aseptic crystallization is primarily used for manufacture of sterile aqueous suspensions. However, if the physical form of the drug is critical to quality of the final product, better control over physical form can be attained by aseptic crystallization because a large variety of organic solvents can be used to control the crystallization process. In aseptic crystallization, the drug is... 

If mixtures of two or more potential guest molecules are offered, the host lattice of 1 allows the selective accommodation of solvent molecules 2). In many cases, a pra-tically 100% discrimination of one guest species (>95% by NMR integration) is achieved by a single crystallization process using /, e.g. from an equimolar two-component solvent mixture. Table 2 summarizes important results (Entries 1-15). 

When we look at the spontaneity of the crystallization process, we need to consider two entropy terms (i) the solute (which decreases during crystallization) and (ii) the concurrent increase as solvent is freed. In summary, the entropy of the solute decreases while the entropy of the solvent increases. 

The crystallization process involves a system (which we are interested in) and the surroundings. In terms of the component entropies in this example, we say AS,iSyiSlcm, is the entropy of the solute crystallizing and that A.S liSlllTOimdmgiS I represents the entropy change of the solvent molecules released. 

The preferred choice for an API crystallization process is a cooling crystallization from a single solvent. This is because temperature and cooling rate are relatively easy to control and to scale up consistently. The decision criteria is based on the solubility profile with temperature and the available yield and productivity. 

The ideal solubility equation (Eq. 2) is the simplest form of model that is applicable to solvent based crystallization process design. Even though the equation excludes non-ideal interactions in the liquid phase, it is still a useful tool in certain circumstances. 

The non-random two-liquid segment activity coefficient model is a recent development of Chen and Song at Aspen Technology, Inc., [1], It is derived from the polymer NRTL model of Chen [26], which in turn is developed from the original NRTL model of Renon and Prausznitz [27]. The NRTL-SAC model is proposed in support of pharmaceutical and fine chemicals process and product design, for the qualitative tasks of solvent selection and the first approximation of phase equilibrium behavior in vapour liquid and liquid systems, where dissolved or solid phase pharmaceutical solutes are present. The application of NRTL-SAC is demonstrated here with a case study on the active pharmaceutical intermediate Cimetidine, and the design of a suitable crystallization process. 

NRTL-SAC has been demonstrated through the case study on Cimetidine as a valuable aid to solubility data assessment and targeted solvent selection for crystallization process design. The average model error is typically 0.5 Ln (x) [1] and is sufficient as a solvent screening tool. Methods that can deliver greater accuracy would increase the value and utility of these techniques. It is impressive in the case of Cimetidine that the NRTL-SAC correlation is capable of reasonable accuracy and predictive capability on the basis of just 2 fitted parameters. Further work to extend the solvent database and optimize the descriptive parameters will be beneficial, and are planned by the developers. 

Polymorphs and solvated crystals is generally observed in pharmacentical indnstry [1], The bioavailability, stability, solnbility, and morphology of the pharmacentical products are very influenced by polymorphs [2-7], therefore the control of the polymorphic crystallization is very important. The crystallization process of polymorphs and solvated crystals is composed of competitive nucleation, growth, and transformation from a meta-stable form to a stable form [4], Furthermore, the crystallization behavior is influenced by various controlling factors such as temperature, supersaturation, additives and solvents [8], In order to perform the selective crystallization of the polymorphs, the mechanism of each elementary step in the crystallization process and the key controlling factor needs to be elucidated [8], On the other hand, we reported for L-Glutamic acid and L-Histidine system previously [4] that the nucleation and transformation behaviors of polymorphs depend on the molecular stractures. If the relationship between molecular stmcture and polymorphic crystallization behavior is known, the prediction of the polymorphism may become to be possible for the related compound. However, detail in such relationship is not clearly understood. 

F. Lewiner, J.P. Klein, F. Puel and G. Fevotte, On-hne ATR-FTIR measurement of supersaturation during solution crystallization processes. Calibrations and applications on three solute/solvent systems, Chem. Eng. Sci., 56, 2069-2084 (2001). 

This is a process mainly used in power plants for separation of solute from liquid by crystallizing the solvent. Either direct refrigeration, or indirect refrigeration can be used. The process removal efficiency is over 99.5%. 

The limited results obtained are not inconsistent with a 1.25 dependence on supersaturation as proposed by Shiau and Berglund (10). The dependence on solvent composition and temperature appears complex and is probably related to the solution viscosity which varies considerably over this range. It thus appears that mass transfer plays a significant part in the crystallization process. Further work needs to be done to clarify these effects. 

Platellke a-form crystals easily separate from the solvent In commercial operation but halrllke 3-form crystals are troublesome because their suspension Is extremely viscous. So the main purpose of this work Is to develop a modified crystallization process to obtain a-form crystal selectively. 

Results for Commercial Operations The content of a-form was up to 99% and average size of the crystal was about 24-35 jum. The formation of 3-form crystal In commercial operation Induced considerable Increase of the viscosity of the suspension. The features of the semi-batch cooling crystallization process are as follows. Even if crystallization temperature is considerably lowered in order to avoid the formation of 3-form crystal, and also even if the feed solution is highly concentrated at high temperature above -SSSK, obtained crystal size is large enough to separate the solvent by centrifuge. 

The monazite sand is heated with sulfuric acid at about 120 to 170°C. An exothermic reaction ensues raising the temperature to above 200°C. Samarium and other rare earths are converted to their water-soluble sulfates. The residue is extracted with water and the solution is treated with sodium pyrophosphate to precipitate thorium. After removing thorium, the solution is treated with sodium sulfate to precipitate rare earths as their double sulfates, that is, rare earth sulfates-sodium sulfate. The double sulfates are heated with sodium hydroxide to convert them into rare earth hydroxides. The hydroxides are treated with hydrochloric or nitric acid to solubihze all rare earths except cerium. The insoluble cerium(IV) hydroxide is filtered. Lanthanum and other rare earths are then separated by fractional crystallization after converting them to double salts with ammonium or magnesium nitrate. The samarium—europium fraction is converted to acetates and reduced with sodium amalgam to low valence states. The reduced metals are extracted with dilute acid. As mentioned above, this fractional crystallization process is very tedious, time-consuming, and currently rare earths are separated by relatively easier methods based on ion exchange and solvent extraction. 

Thorium sulfate, being less soluble than rare earth metals sulfates, can be separated by fractional crystallization. Usually, solvent extraction methods are applied to obtain high purity thorium and for separation from rare earths. In many solvent extraction processes, an aqueous solution of tributyl phosphate is the extraction solvent of choice. 

The interaction between solvents is important. For example, the development of a successful crystallization process for purification and isolation of an organic compound requires the selection of a suitable solvent or solvent mixture to date, no logical method has been estabhshed for determining the best solvent combination. The process chemist or engineer often employs a trial-and-error procedure to identify an appropriate solvent system, the success of which is dependent on experience and intuition. One approach utilizes a group-contribution method (UNIFAC) to predict a... 

Crystallizing particles arriving at the surface will diffuse onto the surface (surface diffusion). As this occurs, some may return to the ambient phase, while some will be caught at kinks or steps (see Section 3.6) on the surface and will be incorporated into the crystal. When these particles are incorporated into the crystal, the solvent component will be dissociated. This process is called desolvation. In solution growth, this process will determine the growth rate. At certain points in these processes, it is necessary to overcome the energy barriers required to climb the respective steps (Fig. 3.5). 

Because the handling of solids is difficult, particularly that of soft organic crystals, several crystallization processes have been developed in which solids do not appear outside the crystallizing equipment, and the product leaves the equipment in molten form. For organic substances, crystalline form and size usually are not of great importance as for products of crystallization from aqueous solutions. If needed, the molten products can be converted into flakes or sprayed powder, or in extreme cases they can be recrystallized out of a solvent. 

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