The liquidus lines characterize the solubility of one compound in the other. Thus, the marked liquidus line is the solubility curve of A in B. The liquidus line of A also starts at the melting temperature of A, TF,A, and in ideal case is identical to the liquidus line of A in Figure 3. Thus, both phase diagrams, one repre- senting melt equilibria and the other solution equilibria of a component in a solvent, can be treated in the same way.
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Moreover, the liquidus line of A in the solvent in Figure 3. When rotating the phase diagram in Figure 3. In the following sections, with regard to their application and the differences in determination, melt and solution equilibria will be discussed separately. The system to be considered is an arbitrary substance A, where pure A in the solid phase, [A]0 , is in equilibrium with A in the liquid phase, [A] This equation describes the temperature dependence of the saturation activity of A in a binary system at constant pressure. Frequently it is found that the second term in Equation 3.
After calculating the liquidus lines for both components of the binary system, the eutectic composition in the phase diagram can be derived from the intersection of the two liquidus lines. To account for deviation from ideality, Equation 3. The liquidus line as demonstrated before corresponds to the ideal solubility line in an arbitrary solvent and hence, allows the prediction of solubilities only as a very rough estimate. Since it is not possible to represent the effects of three variables in a ternary system on a two-dimensional plot, one often considers conditions with constant temperature.
The three components can be graphically represented on a triangular diagram, which might be an equilateral triangle or a right-angled isosceles triangle, as shown in Figure 3. In both cases, the apexes of the triangle represent the pure components A, B, or C. Any convenient concentration unit can be used to scale the axes. Most frequently, weight or mol percent or weight or mol fractions are applied. The amounts of the components are represented by the distance from the triangle sides, as indicated by the grid lines in the phase diagrams in Figure 3.
Considering now this triangle to be the base of a prism and the axis perpen- dicular to the triangle to stand for the temperature variable, a three-dimensional representation of the ternary system is provided. The lowest with components A, B, and C. Shown are the equilibrium. The shaded area depicts an construction of grid lines and scales. The three given temperature. According to the phase rule, in maximum four phases can coexist in equilibrium leaving the system no degree of freedom.
This four-phase invariant is the ternary eutectic characterizing the lowest temperature in the system where the three components as solid phases are in equilibrium with a saturated solution of eutectic composition point P, Figure 3. However, since it is uncomfortable to work with the three- dimensional phase diagrams, often isothermal cuts as indicated by the shaded area in Figure 3.
Analogous to ternary systems, a quaternary system can be represented in a three- dimensional prism, but having a square as prism base with the four components at the corners. An example is given in Figure 3. In order to simplify the interpretation of such quaternary phase equilibria, as for ternary systems, usually isothermal slices of the three-dimensional represen- tation of the phase diagram are considered. Shown are the construction system in the phase diagram. As scale the amount of dimensional representation of a quaternary the particular ions is used.
The four vertical corners AX and BY. The same applies to faces of the prism correspond to the four binary mixtures of BX and AY. The SLE in such systems are most preferably represented as isothermal cuts of the three- dimensional phase diagram shown schematically in Figure 3. The four salts occupy the four corners of the square diagram. Much more information regarding the construction of ternary and quaternary phase diagrams and also other possibilities of their representation can be obtained from the monographs [1,2].
Also, Refs [3,4] should be recommended as excellent source of fundamental knowledge on heterogeneous phase equilibria. In Sections 3. When looking in the appropriate literature, there is a diversity of different forms of melt phase diagrams, in particular for inorganic and metallic systems. On the other hand, much less phase diagrams are reported and described for organic substances. In the context of binary organic mixtures, Figure 3. Generally, one distinguishes between systems exhibiting immiscibility or miscibility in solid state. The latter is the most frequently occurring type, to which more than half of the systems belong.
A simple eutectic system has already been discussed in Section 3. Intermediate compounds can occur as congruently type b or incongruently type c melting compounds characterized by a dystectic invariant open maximum in the phase diagram or by a peritectic invariant concealed maximum , respectively.
Miscibility in solid state, that is, the formation of solid solutions, is less frequent than immiscibility Figure 3. Complete miscibility may be represented in the phase diagram by a melting point minimum case d , a melting point maximum not shown , or, as depicted in case f, without an extreme value.
In addition, partial miscibility can occur in simple eutectic systems e. This might be attributed to i low levels of miscibility that are hardly detectable and ii the low mobility of molecules in solid state making equilibrium measure- ments almost unattainable. An example is described in Section 3. The phase diagrams in Figure 3. In addition, solid—solid equilibria e.
Here, a substance is subjected to a controlled temperature program and a physical or physicochemical property of this substance is measured as a function of temperature. Table 3. Apart from techniques of thermooptical analysis TOA that allow a qualitative or semiquantitative evaluation of the melting behavior, differential scanning calorimetry DSC is the most essential method to establish the binary phase diagram by providing the required detailed quantitative information.
Thus, it is possible to clearly identify, for example, phase transitions where the mass remains constant and degradation or dehydration processes that are connected with a mass loss. X-ray powder diffraction XRPD is a very powerful tool for solid-phase analysis and as temperature-resolved technique capable to directly relate a phase transition to the solid phases present. It supports the study of melt phase diagrams by gaining direct access to polymorphic transitions, the formation of solid solutions, cocrystals, and in case of solution equilibria to solvates.
Parameters measured Methods Optical properties e. With a linear temperature versus time program Figure 3. Due to heat capacity differences of reference and sample, there might be a small but constant deviation between TR and TS, as shown in Figure 3. As reference, an inert material that must not undergo any thermal transformation within the applied temperature range is used, such as alumina or air. Since the reference steadily follows the temperature program, the sample temperature devi- ates in case a thermal effect occurs.
For melting as an endothermal effect, it lags behind the reference temperature Figure 3. From the area enclosed by the DSC curve, the corresponding melting enthalpy can be derived. In the context of a hypothetical binary system, Figure 3. Four examples indicated in Figure 3. As already discussed, single peaks are always provided from a system in invariant state such as melting of a pure substance or an eutectic phase transition. Since D refers to the lowest temperature measured in the system, it can be related to an eutectic invariant at Teu,2.
DSC curve E characterizes the melting of a single Figure 3. The peak can be assigned to an eutectic at a temperature Teu,1, the subsequent broad effect to the dissolution of the excess component 1 in the melt, thus giving both Teu,1 and TLiquidus for the selected composition. Case 4 in Figure 3. It characterizes progressive melting of a solid solution with always two phases present in a binary and thus monovariant system.
The onset and the peak maximum of the thermal effect mark the position of the solidus and liquidus lines. The success of DSC measurements depends on careful sample preparation and selection of adequate measurement conditions. To account for thermal lag effects, a separate temperature calibration at each scan rate is recommended.
A critical point to be emphasized is the preparation of mixtures, which seems to be easy but in fact is really not a trivial task. For this system, it is known that at the 1 : 1 composition in the phase diagram, an intermediate compound a so-called racemic compound, see Figure 3. As obvious, the pattern b representing a 1 : 1 mixture of the two tartaric acid species grinded together matches the pattern of the enantiomer.
Hence, during grinding, no alloying connected with formation of the intermediate compound occurred. Thus, misleading results might be derived from an inadequate sample preparation. The same problem applies to systems with solid solutions. Melting is of course feasible only in case the substance does not undergo any degradation. When recrystallizing from a solvent e. The figure illustrates the L- and D-tartaric acids prepared via influence and the importance of an adequate dissolution and recrystallization from water sample preparation procedure for or acetone as solvent.
The epimers are obtained as an 1 : 1 mixture from chemical synthesis and have to be separated. The phase diagram derived from comprehensive DSC measurements is shown in Figure 3. The system is of simple eutectic type with an eutectic composition at a mol fraction of about 0. The melting temperature of The same applies to the melting enthalpies obtained with Symbols indicate measure- ment data for the liquidus and solidus curves. Their intersection does not perfectly match the experimentally determined eutectic temperature.
A better agreement is achieved when an average melting enthalpy of Arrows illustrate cooling of a melt of an 1 : 1 mixture of the epimers. Reproduced with permission from Ref. Figures 3. The missing eutectic melting in presence of 4. Furthermore, a high-resolution measurement with eight times longer measurement time indicates only trace amounts of the b-phase in the Thus, not always perfectly equilibrated solids could be afforded, although all samples were prepared via similar dissolution and slow recrystallization or freeze-drying procedures. A more adequate evaluation of misci- bility in solid state can be done via construction of a Tammann graph, plotting the heats of fusion of the eutectic effects in the DSC curves DFHeu versus the composition, as shown in Figure 3.
The DFHeu value is highest at the eutectic composition and decreases linearly to both sides of the phase diagram. The intersections with the x-axis i. These boundaries will limit the depletion of the unwanted component by crystallization. When cooling a melt of an 1 : 1 mixture of the epimers, at T0 Figure 3.
On further cooling, the composition of the a-mixed crystals and the melt alter along the solidus and liquidus lines as indicated by arrows. At the eutectic temperature Teu, a crystalline phase of composition C and amount A—B will be in equilibrium with a melt having eutectic composition A of amount B—C.
Shown is sample mass 7. The Setaram. Arrows indicate the boundaries of solubility in solid state. As will be described in Chapter 7, fractional crystallization is capable to further stepwise deplete the unwanted component in the product to the expense of yield. Since the pressure dependence is usually small, it is normally neglected, as already discussed in Section 3. A solution is saturated when the solute concentration is at its solubility limit.
In general, care should be taken when using data from different sources since the reference medium solvent or solution might be different. Furthermore, for interconversion between different composition units, it is recommended to have the density measured at the relevant temperature, in particular when volume-related units are applied. The example shows several possibilities to express a solution concentra- tion of 10 g sodium sulfate in g water.
When using hydrates or generally solvates , the solvent content in the solvate has to be considered in preparation of a solution. It provides information about the solubility of a substance in a particular solvent at different temperatures, and thus is of fundamental importance for development of crystallization processes. For a cooling crystallization, from the solubility difference in the temperature region covered, the possible yield can be determined.
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Thus, it also provides information about the possible phases crystallizing at a particular temper- ature such as solvates or certain polymorphs. As can be seen, different types of solubility— temperature relationships are possible. First, the solubility can strongly increase with temperature as observed for potassium nitrate. Rather smooth increasing solubilities are found for potassium chloride, while the solubility of sodium chloride in water is almost independent of temperature. The absolute solubility values are rather high as expected for those salts in water.
However, solubility can vary widely, even over several orders of magnitude. For example, the solubilities of calcium nitrate and calcium chloride respectively are and Not all solubility curves behave steadily as observed for sodium carbonate and sodium sulfate Figure 3. Dashed lines exemplarily constructed inorganic salts in water. The solubility is given in for the sodium sulfate case represent weight percent. The phases added specify the metastable solubility lines.
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While the solubility increases at low temperatures, at higher temperatures the so-called retrograde solubility occurs. A discontinuity in the solubility curve always denotes a phase change caused, for example, by solvate or polymorphic transitions. This means that above and below the phase transition temperature, different solid phases appear. At temperatures exceeding the transition temperature of In fact, the solubility curve depicted for sodium carbonate is not just one, but represents three solubility curves each belonging to a particular solid phase that intersect at the transition temperatures.
Extrapolated lines characterize metastable solubility curves that can be of importance for special crystallization processes using metastable equilibria for kinetically driven separations. In case of an endother- mal solution enthalpy, the equilibrium shifts with higher temperature to higher solubilities, and thus results in a positive slope of the solubility curve. On the other hand, an exothermal dissolution process leads to a retrograde solubility behavior.
In most cases, the heat of solution is positive, that is, most substances dissolve with absorption of heat. This means that the positive lattice enthalpy exceeds the negative solvation enthalpy or more energy has to be spent to break the lattice than is evolved by solvation.
It allows the prediction of solubilities only from DSC melting data of the compound of interest. For most inorganic substances, this value is known and can be extracted from databases; for organic compounds, less is reported and measurements are necessary. Since Equation 3. Here, the most frequent cases where solubility increases with temperature are shown. It becomes clear that when applying the melting enthalpy in Equation 3. Thus, retrograde solubility can only be explained with the solution enthalpy that can possess negative values. To relate now the solution enthalpy to the slope of solubility curves, in Table 3.
The steep increase of the solubility curve of potassium nitrate correlates with its comparatively high-positive solution enthalpy. Consistently, the weak positive temperature dependence of the sodium chloride solubility is expressed by a low also positive DSH1 value. Negative solution enthalpies occur for anhydrates of salts forming stable hydrates at room temperature such as sodium sulfate and sodium carbonate where hydration is connected with a strongly exothermal effect. Examples are sulfaguani- dine and sparteine, a complicated natural product, both in water.
Discontinuities in the solubility curve originating from polymorphic phase transitions are observed for enantiotropically related polymorphs. The transformation of one polymorph to the Table 3. Enantiotropic phase transitions other one form II with respect to form I , occur reversibly at the phase transition resulting in solubility curves that do not temperature Tt leading to a kink in the solubility intersect csat, saturation concentration.
In case of monotropy b , one of the other is reversible and occurs at the phase transition temperature Tt Figure 3. In contrast, the solubility curves of monotropic forms do not intersect. Independent on temperature one of the two polymorphs is always metastable with respect to the other and thus characterized by higher solubilities Figure 3. For more details, refer to Chapter 5. In Figure 3. Some solubilities exceed the ideal line, some fall below. The solubility in ethylacetate matches almost the ideal values; addition of heptane lowers the solubility successively.
The slopes of the real solubility lines seem to deviate not that much from the ideal case. However, the solution enthalpies derived from the curves slope vary between In solvates, the solvent is part of the crystal structure, that is, coordinated in or accommodated by the crystal structure, thus representing a single phase. According to the differences in the crystal structure, solvates and the appropriate unsolvated solid exhibit different physicochemical properties such as melting point, solubility, dissolution behavior, processability, and stability.
Sometimes the terms solvate and polymorph are mixed, which probably happens due to their behavior with respect to properties. However, both fall in different categories, as shown in Figure 3. Polymorphism always occurs in a unary system. The ideal solubility curve was Different polymorphs are just different crystalline forms of the same chemical compound having same chemical formula.
Thus, they are all represented on the pure compound side of the phase diagram Figure 3. Contrarily, solvates refer to the binary system of a compound and a solvent and, therefore, are represented as intermediate compounds between the pure compound and the solvent in the phase diagram Figure 3. Hence, they differ in chemical formula. Each solvate may have own polymorphic forms of same chemical formula , which then again belong to the unary system of the intermediate compound.
As already introduced, phase transitions between different solvates or between a solvate and the unsolvated compound as well as polymorphic transformations can be recognized by discontinuities in the solubility curves. Examples are shown in Figure 3. Cocrystals are intermediate compounds of two or more discrete neutral molecular species that are, in their pure forms, solids at ambient temperature. This distinguishes cocrystals from solvates where one of the constituents of the intermediate compound is a solvent that is liquid at ambient temperature.
Each hydrate has its own solubility characterized by their solubility curves in water. Solvates are indicated by vertical common. The existence regions are bordered by lines in the binary system, thus characterizing horizontal lines starting from the pure intermediate compounds that can melt component side specifying the phase transition congruently or incongruently. In the case temperatures of the particular polymorphs, Tt shown, different hydrates of magnesium nitrate 1, 2,.
Thus, they are represented in the phase diagram similar to solvates. Since the building blocks are neutral molecular species, cocrystals are no salts. In the last years, cocrystals as a particular solid-state form have become an increasingly popular issue in the pharmaceutical industry, since they offer an opportunity to improve and tailor the physicochemical characteristics of drugs, such as solubility, shelf life, dissolution rate, and bioavailability.
An example was recently demonstrated in Ref. The solvent most often used is water due to its distinct solvent properties and, from application-oriented view, as it is readily available, cheap, and harmless. It is the preferred solvent for crystallization of inorganic compounds and whenever feasible also for organic substances. Sometimes mixed solvents, that is, mixtures of two or more solvents, show more favorable solution properties for a particular solute than just one solvent. Therefore, like temperature, the solvent composition is a common variable in designing a crystallization process.
In antisolvent crystallization, the application of an additional solvent antisolvent is targeted to the reduction of the solubility of a substance in order to cause its crystallization. In case of a weak solubility—temperature relationship, as e. For example, in the well-known hot leaching process, potassium chloride as target compound is separated from its mixtures with sodium chloride using the differences in the solubility functions Figure 3.
Impurities can also affect the solubility of a solute of interest. Here, both a solubility enhancement and a solubility decrease occur. When electrolytes are involved, the terms salting-in and salting-out apply. Small impurity contents might be evaluated together with the solvent. The representation and application of ternary SLE will be addressed in Section 3. Even then measured solubilities can vary since the solid substance could originate from diverse batches and, therefore, be of different purity. Most industrial crystallization processes involve solutions with impurities and both their identity and content might vary, for example, due to alterations in the production process or the heterogeneous composition of ores as starting material.
Therefore, it is desirable to know the solubility of a given solute in the actual working solution with the impurities present and it is very unlikely that such data are available in the literature. This particular solubility solutions lines 3 and 4. The figure illustrates behavior is used in the so-called hot leaching both the influence of a further compound process to separate KCl and NaCl from sylvinite considered as impurity on solubility of a crude salts. It is obvious from the solubility certain substance and the application of curves that cooling a solution saturated with different solubility behaviors for separation both salts point of intersection of lines 3 and 4 purposes.
Furthermore, contrary to the solubility curve of Reproduced with permission from Ref. The most suitable method for a given system depends on various subjects such as available amount of substance which is often a limiting factor during early development stages , kind of solvent e. Generally, solubility data can be determined in two ways, as illustrated in Figure 3.
The two approaches differ in the temperature regime applied. In case 1 , the sample is analyzed at a constant temperature isothermal technique ; in case 2 , the sample is subjected to a slow controlled heating polythermal technique. In the following sections, examples of isothermal and polythermal techniques for solubility measurement are presented. Here, advantages and weaknesses of the particular methods as well as the question, how to guaranty equilibrium conditions, are addressed. Particles from the solid phase pass into the liquid phase and vice versa Figure 3.
Here, diffusion resistances in the solution—crystal interface and surface integration resistances have to be overcome. This could be a real obstacle when working with heavily viscous solvents. Achieving equilibrium conditions in solubility equilibria might take a considerable period of time, in particular when the dissolution kinetics is low. Dissolution rates generally become slow close to saturation points. In isothermal measurements, the time required to establish equilibrium condi- tions teq can be determined in a simple experiment illustrated in Figure 3. The solvent is thermostated at the desired temperature and stirred at moderate rate.
After introducing an excess amount of solid into the solvent, samples of clear solution are removed at different times and analyzed for concentration subsequently. When the solution concentration reaches a constant value, saturation is achieved and the minimal equilibration time for that temperature can be derived from the concen- tration—time plot, as given in Figure 3. For polythermal measurements, different heating rates must be checked for the particular system in order to determine the optimal one.
Often a compromise between a very low heating rate with weak signal strength and a higher heating rate with stronger signal strength but probably nonequilibrium conditions has to be made. It involves the following steps: 1 Sample preparation and sample pretreatment. The measurement is performed in a closed sample vessel to prevent loss of solvent by evaporation.
The solvent and an excess of the solute or solutes are introduced in the sample vial and the stirred solution is subjected to the pretreatment step described in Section 3. After recrystallization, the measure- ment temperature is adjusted. The suspension is kept at constant temperature for at least the equilibration time teq already determined. Optimal mixing of the suspension should be examined repeatedly during equilibration.
Slight inaccuracies of the temperature affect the correctness of the solubility value in particular for strong solubility— temperature relationships. The identity of the solid phase should be characterized as fast as possible after solid—liquid separation in order to catch e.
Saturation concentrations measured in solubility experiments always refer to the solid phase that was in equilibrium with the solution analyzed. In case of multicomponent systems, that is, more than one solute in the saturated solution, additional analysis of the solid-phase composi- tion allows to verify the overall mass balance. Usually it is also feasible to measure multiple csat—T data pairs with one initial suspension provided the suspension density is not too high. The temperature is stepwise increased after each equilibration and concentration measurement.
In addition, the presence and identity of the solid phase have to be ensured and checked, respectively. For higher throughput of samples, a certain automation of solubility measure- ments is feasible. For all vials, electromagnetic stirring is provided. Furthermore, since four vials are always arranged in a separate reactor block, four different temperature levels can also be applied simultaneously.
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For detection, visual observation e. Since it is a dynamic method, the results depend on dissolution kinetics of the particular system. In general, polythermal measurements are easier to automate since just a temperature has to be followed and no special analytical technique is required. The above-mentioned Crystal16TM multiple reactor system can also be used to perform such kind of measurements. The dis- advantage of such a kind of measurements is that there is no characterization of the solid phase involved. Therefore, separate experiments for solid-phase analysis must be considered to properly reassign the saturation temperatures measured to the appropriate solid phases.
The same applies when using calorimetric detection techniques. Here, on heating, the heat consumed during dissolution of a known amount of solute in a certain amount of solvent is measured. When ensuring close-to-equilibrium experiments, from the thermal dissolution effect, i the saturation temperature of the mixture analyzed Tend Figure 3. The latter requires knowledge of the solubility at T1. Such measurements can be performed in reaction calorimeters or classical DSC instruments. Reaction calorimetry usually necessitates higher sample amounts, but allows stirring the mixtures.
From previous experiments, heating rates between 0. More information may be extracted from literature sources [9,10]. Shown is the heat flow HF corresponds to the course of the solubility measured along a linear heating program. On curve. The end of the thermal effect Tend heating, the solute dissolves in the solvent, and marks the saturation temperature of the under equilibrium conditions, the amount mixture studied. Thus, for systems forming either polymorphs or solvates, these techniques do offer some room for error.
The same applies to the references added to extract more information.
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A more general overview of model development by means of the most frequently applied models in process development is given in Ref. An application-oriented introduc- tion is given in Ref. In principle, such methods are recommended to be applied as complementary tools to experimental solubility determination that can help to reduce the experimental efforts required. Lei, B. Chen, C. Li, H. Liu, Chem. Hahnenkamp, G. Graubner, J. Gmehling, Int. Weidlich, J. Gmehling, Ind. Gmehling et al. Klamt, In: P. Schleyer Ed. Lin, S. Sandler, Ind. Grensemann, J. Kleiner, F. Tumakaka, G.
Sadowski, In: X. Lu, Y. Ruether, G. Sadowski, J. Tumakaka, I. Prikhodko, G. Sadowski, Fluid Phase Equilib. Gmehling, B. Renon, J. Chen, P. Crafts, Ind. Deviations between the ideal and real curves slopes e. Furthermore, a reasonable linearity of the plot allows extraction of solubility data in the temperature range studied. It is caused by a miscibility gap in liquid state, as illustrated in Figures 3. A miscibility gap in liquid state is frequently observed when an organic compound with hydrophobic properties is mixed with water, or vice versa, a salt of an organic component with hydrophilic properties is added to an organic hydrophobic solvent.
A miscibility gap can occur under stable equilibrium condi- tions, and thus is represented in the equilibrium phase diagram, or might charac- terize metastable equilibria. Therefore, the knowledge of the phase diagram of the particular system is essential i to identify the presence of a miscibility gap in liquid state and the corresponding liquid—liquid phase boundary and ii to derive possible existence regions of metastable miscibility gaps. At Tm, a third phase, monotectic phase transition in a binary system. This three-phase invariant is When cooling a liquid of a composition called monotectic invariant, and the between x1 and x2 and reaching the phase corresponding temperature Tm monotectic boundary of the miscibility gap, a second liquid temperature.
The dashed lines extrapolating the phase appears. On further cooling, the phase boundary of the miscibility gap indicate compositions of the two liquid phases l1 and l2 metastable equilibria that may impair a alter along the phase boundary of the miscibility particular separation process.
In case nucleation is initiated. If the phase boundary The two liquid phases differ in their of the miscibility gap is closely related to the composition specified by the tie line and metastable zone here of A , the liquid—liquid nucleation may occur in both phases. A reasonable explanation is the existence of a metastable miscibility gap located below the solubility curve of the solute which is passed when nucleation starts. This situation is illustrated in Figure 3.
Oiling-out, in particular when unexpected, that is, in metastable conditions, is undesired in industrial applications. The high supersaturation present at the onset of nucleation can lead to very small particles, subsequent agglomeration, low purity of the crystals obtained, and the formation of unwanted polymorphs. In case of a stable miscibility gap in the phase diagram, one can check if it is reasonable to work at conditions outside the liquid—liquid phase boundary e.
If not, different solvents might have to be considered. More practical aspects are addressed in Ref. A very interesting case of oiling- out for an API intermediate has recently been published in Ref. Examples are a single impurity in a solute—solution system, the separation of diastereomeric salts or the two enantiomers of a chiral system, and the application of two solvents where often the solute is highly soluble in one and only slightly soluble in the other e.
In these industries, the request for pure enantiomers instead of the racemates containing the enantiomers in an 1 : 1 ratio as mostly provided from chemical synthesis is steadily increasing. In this chapter, the ternary system of the two enantiomers and a solvent will be considered as an example of ternary solution equilibria. Since the two enantiomers of a chiral system have same melting points and melting enthalpies, their melt phase diagrams are symmetrical to the 1 : 1 i.
The same applies to the solubility diagrams of the enan- tiomers as shown in Figure 3. Therefore, in general only one half of the phase diagram has to be measured. The latter are denote the two enantiomers. As can be seen, the shape of the solubility isotherms in the ternary system is clearly related to the liquidus curves in the binary system. The light gray areas in the ternary phase diagrams represent the existence regions of the appropriate enantiomers, where in equilibrium the pure enantiomer as solid phase can be crystallized.
The dark gray area below the solubility isotherm of the racemic compound corresponds to the existence region of this intermediate compound, that is, the racemic compound is the solid phase crystallizing from solutions of compositions in that region. The two-phase regions are separated by a three-phase region, where a pure enantiomer can only be crystallized under kinetically driven, out-of-equilibrium conditions. We could read books on the mobile, tablets and Kindle, etc. Hence, there are lots of books coming into PDF format.
Right here websites for downloading free PDF books which you could acquire as much knowledge as you wish. Today everybody, young and aged, should familiarize themselves along with the growing eBook business. Ebooks and eBook readers provide substantial benefits more than traditional reading.
Ebooks slice down on the make use of of paper, as advocated by environmental enthusiasts. There are no fixed timings for study. In demarcation to alternative PAT in the field of industrial crystallization, advantages, potentials, and limits are outlined and discussed with particular reference to the applicability of the technology and the material systems together with the transferability to other substances as well as the scale-up ability of the underlying mathematical model.
Additionally, the reliability of the UCM technique is validated by comparing the results with established and commercially available PAT for the solid phase. Process Res.
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