Crystallization common problems

Because of their importance as basic primary centers, we will now discuss the optical bands associated with the F centers in alkali halide crystals. The simplest approximation is to consider the F center - that is, an electron trapped in a vacancy (see Figure 6.12) - as an electron confined inside a rigid cubic box of dimension 2a, where a is the anion-cation distance (the Cr -Na+ distance in NaCl). Solving for the energy levels of such an electron is a common problem in quantum mechanics. The energy levels are given by... 

Crystallization processes can be used for separation, purification, or concentration of a solute, or because a particular product needs to be used in solid form, or as a component of an analytical procedure. Common requirements for accomplishing these functions are that the crystals must be produced with a particular size distribution and having a specified shape and purity. Almost all crystallizer operating problems are defined in terms of the product not meeting one of these criteria. 

Simple crystallization of an impure solid is a routine operation, which nevertheless requires care and good judgement if good results are to be obtained. The basic procedure can be broken down into six steps, which are listed below, together with some tips on how to overcome common problems. 

Karl Fischer Titration Moisture content of reference standards is commonly and accurately determined by Karl Fischer (KF) titration. KF titration determines total water content, including both the free water and water of hydration trapped in the crystal structure. Coulometric KF-titration is the most sensitive application of the method and is normally used for the small amounts of water found in reference standards. A volumetric technique is available for samples containing large amounts of water. Interference is a relatively common problem in KF titration and thus, due caution must be exercised in the interpretation of KF results. Reagents have been designed to cope with interfering functional groups.48-50... 

A common problem in macromolecular crystallization is inducing crystals to grow that have never previously been observed. The single major obstacle to obtaining any crystals at all is, however, ensuring the formation of stable nuclei of protein crystals. In cases where the immediate problem is growing crystals, attention must be thus directed to the nucleation problem, and any approach that can help promote nucleation should be considered. 

Honey is natural, but jam and syrup are artificial supersaturated solutions in which sugar is the main solute. For example, syrup, a highly concentrated solution of sucrose (table sugar) in water, is made by heating the solution to almost the boiling point. The crystallization of the excess solute, sugar, is a common problem for these substances. 

As discussed in Chapter 1, polymorphism is a common problem encountered in the synthesis of pharmaceuticals. In the process development for a drug candidate of reverse transcriptase inhibitor, six crystal forms were identified. The first pilot plant batch produced all Form III, not the desired Form I. The purpose of this example is to illustrate the development of a robust crystallization process to consistently grow the desired crystal form. 

Here are some of the common problems that arise with the crystals, and how they are dealt with. To spot these possible problems, the crystals are first left on the plate to dry out, and then transferred to glass jars or plastic baggies. 

The candy technologist, in manufacturing the various types of product ranging from hard candy and caramel to liquid-center chocolates, employs many of the physical and chemical properties of sucrose (71). In hard candies, crystallization and stickiness are the two most common problems limiting shelf life (23). Use of the proper amount of an acidic doctor, such as cream of tartar, causes enough... 

Data on the effective metastable limit at the conditions you are interested in (composition, cooling rate, and stirring) are important because you normally wish to operate a crystallizer away from the edge of the effective metastable zone. As we will see in later chapters, formation of small crystals, which are known as fines, is a common problem. Fines cause filtration problems and... 

There are several common problems encountered in the use of crystallization in the pharmaceutical industry (1) the control of supersaturation (and PSD) in a batch crystallizer (2) the effective use of seed (3) efficient measurement of solubilities in multiple solvent systems to maximize purification and yield and (4) identification and retention of the most stable polymorphic form. 

This section will give a brief summary of common problems in crystal structures. 

The following chapters are intended to address the most common problems in a way that can easily be understood by scientists who have basic crystallographic knowledge and a minimum of experience refining simple crystal stmctures. 

A tailored modifier does not always have to be deliberately added to a crystallizing system it may already exist, e.g., as a synthesis by-product of a chemical reaction. If its presence causes a crystal habit problems, it must be removed or deactivated. On the other hand, it may have a beneficial effect. These are both commonly encountered cases in the manufacture of organic chemicals. A simple, but industrially important, example is the effect of biuret on the crystallization of urea (Davey, Fila and Garside, 1986). In the synthesis of urea (NH2CONH2) from ammonia and carbon dioxide a small amount of biuret (NH2CONHCONH2), a condensation dimer, is formed. The presence of biuret is actually beneficial because from pure aqueous solution urea crystals form as elongated [001] needles that are difficult to process. Biuret retards growth in the... 

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