Crystals surface area

It has been shown that an increase in crystallizer residence time, or decrease in feed concentration, reduces the working level of supersaturation. This decrease in supersaturation results in a decrease in both nucleation and crystal growth. This in turn leads to a decrease in crystal surface area. By mass balance, this then causes an increase in the working solute concentration and hence an increase in the working level of supersaturation and so on. There is thus a complex feedback loop within a continuous crystallizer, illustrated in Figure 7.11. 

It was suspected that two mechanisms could lead to an increase in the impurity content of crystals as supersaturation increased. The first is through nucleation i.e., an increase in supersaturation leads to greater nucleation rate and, concomitantly, larger numbers of crystals and higher crystal surface areas. As the crystals recovered in the present experiments were washed with acetone, surface impurities are not thought to have been important in the results presented here. 

The main processing options open to the crystallizer designer are the solubility gap (transition temperature, acid content), the operating temperature and the values of the rate coefficients (affected by Impurities) and crystal surface areas (eg. altering crystal content). The computer model generated In this study allows these effects to be evaluated. 

Ice Crystal Growth. In order to quantify these results for the production of large disc and spherical crystals, seversd batch experiments on 6% lactose solutions were undertaken. The experimental conditions and results are shown in Table II. In these experiments, nuclei were generated at -2.5 C (except for Run Sa at -4.0°C) and input to the batch crystallizer controlled at various refirigerant temperatures. As these crystals grew, the total crystal surface area was controlled manually in order to maintain a heat balance for a constant value of the refrigerant temperature. Slurry removal rate for these experiments... 

A = crystal surface area per litre of the crystallizer content (m2/l)... 

The crystal surface area. A, could be calculated from the specific crystal surface area. As (m2/g of crystals) by equation (3). 

As, the specific crystal surface area (m2/g of solids) can be obtained by the method recommended in the Coulter Counter Model D Operating Manual ... 

Equation (6) indicates that secondary nucleation is significantly affected by the crystal surface area A (m2/l). The nucleation process is usually viewed as a process where copious amounts of fines are produced, resulting in a corresponding increase in the specific crystal surface area (m2/g) and crystal surface areaA olume of the crystallizer content (m /l). Results obtained in this study concur with this nucleation view. However, Brown (9) reported that nucleation can be suppressed at high crystal surface areas ( 20 m2/l). Brown s observation was not evident in this study though the seed density of 200 g/litre used in this study had a surface area of 25 m2/l. The lower dependence of second nucleation on supersaturation or concentration driving force, AC, in comparison to crystal surface area. A, is obvious from equation (6). 

At a given temperature, the crystal surface area has a bigger contribution to the nucleation rate than AC. The low dependence of the nucleation rate on the concentration driving force implies that the secondary nucleation of alumina trihydrate is removal-limited. 

Suppose that the batch crystallizer is seeded with a mass of crystals with a uniform size of Lseed. The number of seed crystals is Nseed, and, as the operation is to be free from nucleation, the number of crystals in the system remains the same as the number of seed crystals. The initial values of total crystal length, total crystal surface area, total... 

A Crystal surface area d. Equivalent spherical diame-... 

The black compound which is oxidized to goethite has large platy crystals (surface area ca. 10 m /g), shows two strong basal reflections at 1.04 and 0.504 nm, and has an Fe /Fe ratio of ca. 0.8-1. Thus, it appears to be a hitherto unknown layer compound akin to the well-known green rust phases (see chap. 13). 

The results of the base case simulation are depicted in Figure 5 and 6. It can be seen that crystals with a mean size of 265 pm can be produced with a solid fraction of 27%. The supersaturation and growth rate show a peak in the beginning which can be explained by the supersaturation build up from the increasing concentration in the ML compartment and supersaturation consumption by the increasing crystal surface area. 

Although widely practiced for production of industrial chemicals, continuous evaporation for crystallization is rarely if ever used in pharmaceutical operations. Although continuous operation has the advantages of using massive seeding and increased control of supersaturation and the crystal surface area, the throughput necessary for its application is rarely, if ever, achieved for final bulk drug substances. In addition, continuous operation to achieve the conditions for crystallization (as discussed above for resolution of optical isomers) is often not... 

Both nucleation and growth almost always proceed simultaneously. In general, nucleation will dominate when supersaturation, either local or global, is close to or greater than the upper limit of the metastable region. Growth can dominate at low supersamration and in the presence of a sufficient crystal surface area. 

Goals. Consistent control of crystal surface area and crystal shape without charging dry seed from hatch to batch... 

This crystallization procedure ensures a growth-dominant strategy in order to consistently reach the desired purity and final PSD. The goal of this example was to control the final crystal surface area and shape in order to optimize the dissolution rate of the compound. 

---