Suspensions crystal growth

Gahn, C. and Mersman, A., 1999b. Brittle fracture in crystallization processes Part B. Growth of fragments and scale-up of suspension crystallizers. Ibid. pp. 1283-1292. 

Chapters 15 through 17 are devoted to mathematical modeling of particular systems, namely colloidal suspensions, fluids in contact with semi-permeable membranes, and electrical double layers. Finally, Chapter 18 summarizes recent studies on crystal growth process. 

Stabilization of emulsions Stabilization of suspensions Stabilization of foams Control of crystal growth... 

Pharmacists should also take a dim view of changes in the particle size, size distribution, or particulate nature of semisolid suspensions. They are the consequence of crystal growth, changes in crystalline habit, or the reversion of the crystalline materials to a more stable polymorphic form. Any crystalline alteration can lead to a pronounced reduction in the drug-delivery capabilities and therapeutic utility of a formulation. Thus, products exhibiting such changes are seriously physically unstable and unusable. 

JE Carless. Dissolution and crystal growth in aqueous suspension of cortisone acetate. J Pharm Pharmacol... 

A surfactant is a surface-active agent that is used to disperse a water-insoluble drug as a colloidal dispersion. Surfactants are used for wetting and to prevent crystal growth in a suspension. Surfactants are used quite extensively in parenteral suspensions for wetting powders and to provide acceptable syringability. They are also used in emulsions and for solubilizing steroids and fat-soluble vitamins. 

Growth and nucleation interact in a crystalliser in which both contribute to the final crystal size distribution (CSD) of the product. The importance of the population balance(37) is widely acknowledged. This is most easily appreciated by reference to the simple, idealised case of a mixed-suspension, mixed-product removal (MSMPR) crystalliser operated continuously in the steady state, where no crystals are present in the feed stream, all crystals are of the same shape, no crystals break down by attrition, and crystal growth rate is independent of crystal size. The crystal size distribution for steady state operation in terms of crystal size d and population density // (number of crystals per unit size per unit volume of the system), derived directly from the population balance over the system(37) is ... 

This results In a set of first-order ordinary differential equations for the dynamics of the moments. However, the population balance Is still required In the model to determine the three Integrals and no state space representation can be formed. Only for simple MSMPR (Mixed Suspension Mixed Product Removal) crystallizers with simple crystal growth behaviour, the population balance Is redundant In the model. For MSMPR crystallizers, Q =0 and hp L)=l, thus ... 

It Is unknown whether suspended a-form crystal or 3-form crystal In the saturated solution displays a solid-solid transformation or not. The reason for above experimental results may be assumed as follows In the standpoint of Industrial crystallization. Since 3-form crystal Is less soluble than a-form crystal at high temperature above 284K. The state that a-form crystal Is suspended In the saturated solution Is considered to be supersaturated for 3-form crystal. So the state has the potential to take place primary nucleatlon and crystal growth for the 3-form. In this way, 3-form crystal may be produced In the suspension of a form crystal. Rewarding to the formation of 3-form crystal, a part of a-form crystal suspended may be dissolved. Opposite phenomena may take place at low temperature below 284K. 

Since cortisone acetate exists in several polymorphic forms, when aqueous suspensions are prepared, all particles should be converted to the most stable form to prevent undesirable crystal growth [64]. 

Similarly to the solubility of active drugs, the solubility of surfactants that were used in CFC systems has significantly changed. Surfactant solubility in HFA 134a ranges from 0.005% to 0.02% w/v, much lower than the concentration required to stabilize suspensions (0.1-2.0% w/v) (24,42). The surfactants can be solubilized with the addition of cosolvents such as ethanol. However, it is most likely that cosolvents will be incompatible with suspension formulations because drug solubility will also be promoted and crystal growth will occur. 

In an alternative process, the starting material consists of needle-shaped particles of a-Fe203 instead of FeOOH pigments [5.9], [5.10]. The synthesis is carried out in a hydrothermal reactor, starting from a suspension of Fe(OH)3, and crystal growth is controlled by means of organic modifiers. 

K for 24 h. The crystalline material was recovered after suspension in 5% NaOH solution by filtration (Kuznicki, 1989, 1990 Kuznicki et al., 1991a, 1991b, 1991c, 1993). The synthesis of ETS-10 has also been carried out by the use of tetramethylammonium salts, with a significant acceleration of crystal growth (Valtchev et al., 1994). These titanium silicates contain Tilv in octahedral coordination and do not have the catalytic properties of the titanium silicates discussed previously (see Sections III and VI). 

Since many undesirable changes in pharmaceutics arise from nucleation and crystal growth, impurities (either added intentionally or inadvertently) can modulate or suppress these processes. This may give rise to inhibition of crystal growth in suspensions, emulsions, and ointments, and may also inhibit polymorphic transitions. 

In his analysis of this system, Saeman (SI) made the following basic assumptions (a) The suspension is completely mixed, (b) The system is operating at steady state, (c) The numerical rate of withdrawing product plus fines equals the nucleation rate, (d) The weight rate of withdrawing product plus fines equals the crystallization rate, (e) The shape factor is constant (linear crystal size proportional to cube root of volumetric size). (f) The linear rate of crystal growth is constant and proportional to the supersaturation. 

Crystal growth of ZnS can be achieved by using a hydrothermal process instead of by calcination. The raw lithopone is precipitated with a slight excess of sulfide at pH 8.5. The pH is then adjusted to 12-13 with sodium hydroxide solution, and 0.5% sodium carbonate is added. The suspension is then autoclaved for ca. 15-20 min at 250-300 °C. In contrast to the wurtzite structure of the calcined product. 

Ziller, K.H. Rupprecht, H. Control of crystal growth in drug suspensions 1. Design of a control unit and application to acetaminophen suspensions. Drug Dev. Ind. Pharm. 1988, 14, 2341-2370. 

The influence of crystal habit on performance of suspension dosage form can be envisaged to be more pronounced than other dosage forms because of greater space available for reorientation and packing of dispersed particles. Furthermore, selection of a stable habit is essential to avoid crystal growth that leads to physical instability during the shelf life of suspensions. 

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