CSD

The two major databases containing information obtained from X-ray structure analysis of small molecules are the Cambridge Structural Database (CSD) [25] and the Inorganic Crystal Structure Database (ICSD) [26] both are available as in-house versions. CSD provides access to organic and organometallic structures (mainly X-ray structures, with some structures from neutron diffraction), data which are mostly unpublished. The ICSD contains inorganic structures. 

The Cambridge Structural Database (CSD) contains crystal structure information... 

For each crystallographic entry in the CSD, the following information is stored ... 

CSD Cambridge Crystallographic Data Centre organic, me-talorganic crystal structures numeric 257000 experi- ments Cambridge Crystallographic Data Centre commercial CD-ROM periodi- cally www.ccdc.ca- rn.ac.uk... 

TA Instmments CSD Controlled Stress Rheometer D-E 10-2-10 10-2 -5 X 10 good TA Instmments, New Castle, Del. 

It is often important to control the CSD of pharmaceutical compounds, eg, in the synthesis of human insulin, which is made by recombinant DNA techniques (1). The most favored size distribution is one that is monodisperse, ie, all crystals are of the same size, so that the rate at which the crystals dissolve and are taken up by the body is known and reproducible. Such uniformity can be achieved by screening or otherwise separating the desired size from a broader distribution or by devising a crystallization process that will produce insulin in the desired form. The latter of these options is preferable, and considerable effort has been expended in that regard. 

Population density (n) has dimensions number/(volume)(length) it is a key quantity in the discussion of CSD, a function of the characteristic crystal dimension E, and it is defined so that it is independent of the magnitude of the system. When a total population density is used, the symbol is n and the units are number/length. Population density is defined by letting AiVbe the number of crystals per unit system volume in a size range from E to L + AL, so that... 

An average crystal size can be used to characterize a CSD. However, the average can be determined on any of several bases, and the basis selected must be specified for the average to be usehil. More than 20 different averaging procedures have been proposed, yet none is generally satisfactory or preferred (5). 

Preferential Removal of Crystals. Crystal size distributions produced ia a perfectiy mixed continuous crystallizer are highly constraiaed the form of the CSD ia such systems is determined entirely by the residence time distribution of a perfectly mixed crystallizer. Greater flexibiUty can be obtained through iatroduction of selective removal devices that alter the residence time distribution of materials flowing from the crystallizer. The... 

The effects of each selective removal function on CSD can be described in terms of the population density function n. It is convenient to define flow rates in terms of clear Hquor, which requires the population s density function to be defined on a clear-Hquor basis. In the present discussion, only systems exhibiting invariant crystal growth are considered. 

Add selected quantity of seed crystals having specified CSD. ... 

Uniform CSD spread closely around dominant size... 

Fig. 20. CSD characteristics from batch crystallization without seeding.

CSD is bimodal with distribution spread closely around dominant size of seed crystals and broadly around crystals formed... 

Mote quantitative relationships of the CSD obtained from batch operations can be developed through formulation of a population balance. Using a population density defined in terms of the total crystallizer volume rather than on a specific basis (n = nU), the general population balance given by equation 42 can be modified in recognition of there being no feed or product streams ... 

General solution of the population balance is complex and normally requires numerical methods. Using the moment transformation of the population balance, however, it is possible to reduce the dimensionality of the population balance to that of the transport equations. It should also be noted, however, that although the mathematical effort to solve the population balance may therefore decrease considerably by use of a moment transformation, it always leads to a loss of information about the distribution of the variables with the particle size or any other internal co-ordinate. Full crystal size distribution (CSD) information can be recovered by numerical inversion of the leading moments (Pope, 1979 Randolph and Larson, 1988), but often just mean values suffice. 

Solution enters the vessel (Figure 3.4) and is well-mixed throughout i.e. all eonditions - temperature, eoneentration, veloeity, turbulenee ete. are uniform (homogeneous). Supersaturation is generated (by evaporation, eooling, ete.) and nuelei form and grow into erystals. Sinee erystals have varying probabilities of residenee time in the vessel, however, the slurry exhibits a erystal size distribution (CSD). Produet slurry is eontinuously withdrawn and has exaetly the same eomposition as the vessel. 

The CSD from the continuous MSMPR may thus be predicted by a combination of crystallization kinetics and crystallizer residence time (see Figure 3.5). This fact has been widely used in reverse as a means to determine crystallization kinetics - by analysis of the CSD from a well-mixed vessel of known mean residence time. Whether used for performance prediction or kinetics determination, these three quantities, (CSD, kinetics and residence time), are linked by the population balance. 

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