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Nucleation inhibitors

In general, a nucleation inhibitor should be considered to improve the stability of the supersaturated solutions. The pharmaceutical polymers, complexing agents, and surfactants have been used widely forthis purpose (Brewster et al., 2007). [Pg.124]

Other examples of application of this concept are presented in Table 7.2. It should be mentioned that the resolutions described in Table 7.2 intentionally are performed in nonoptimized conditions. Therefore, further improvement of the resolution efficiency should be possible when nucleation inhibitors are applied. The procedure clearly offers the opportunity to improve the outcome of a classical resolution without the need for stoichiometric mixtures of resolving agents. The original DR procedure as well as molecular modeling calculations32 can help in identifying efficient nucleation inhibitors. [Pg.110]

The supramolecular assembly process can be controlled so that the precursor nuclei in solution adopt a structure that resembles the structure of the desired crystalline modification. " This concept has been used in the design of nucleation inhibitors to prevent growth of the stable polymorph and enhance the growth of the metastable polymorph. Davey and coworkers have explained the solvent dependent polymorph appearance of sulfathiazole by analyzing the intermolecular interactions in the various polymorphic structures, and comparing them with the supramolecular assemblies that could exist in the different solvents. In this case, however, the solvent dependent selective crystallization of a polymorph was not correlated with solubility. [Pg.843]

In this process, a feedstock containing drug (for example, 2%), with or without excipient(s) such as Pluronic FI27, nucleation inhibitors such as PVP... [Pg.2575]

Sato et al. (1981) measured the solubility of amorphous substance by adding a nucleation inhibitor, but the measured solubility could have been aflhcted by the presence of the nucleation inhibitor. [Pg.20]

Torbeev, V.Yu., Shavit, E., Weissbuch, Leiserowitz, L Lahav, M. Control of crystal polymorphism by tuning the structure of auxihary molecules as nucleation inhibitors. The /3-polymorph of glycine grown in aqueous soluhons, Crystal Growth Design. 5(6) (2005) 2190-2196. [Pg.191]

Nudelman E, Pieterse K, George A, Bomans PHH, Friedrich H, Brylka LJ et al (2010) The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors. Nat Mater 9 1004-1009... [Pg.342]

The rate of nucleation of a solution or melt can be affected considerably by the presence of mere traces of impurities in the system. However, an impurity that acts as a nucleation inhibitor in one case may not necessarily be effective in another indeed it may even act as an accelerator. No general rule applies and each case must be considered separately. [Pg.192]

Homogeneous nucleation rates can be controlled by gaseous additives. Particle morphologies, particle size, and size distributions as well as temperature thresholds for nucleation may vary considerably with small amounts of nucleation inhibitors or nucleation boosters as is shown in Figure 6.17 for the case of Ti02 formation by combustion of TiCL. ... [Pg.220]

The inclusion of nucleation inhibitors such as silicon dioxide can modulate nu-cleation process, thus prolonging the suspension stability. Particle size control of amorphous formulations is essential for homogeneity and withdrawability for dosing accuracy. [Pg.345]

For a weakly acidic drug, AMG009 with poor intrinsic solubility (0.6 (cg/mL), Bi et al. (2011a, 2011b) prepared solid dispersions by using various nucleation inhibitors, such as HPMCE5 LV, HPMC KlOO LV, plasdone K-17 (PVP K17) pH-modiflers, such as sodium carbonate, sodium bicarbonate, tromethamine, sodium acetate, sodium phosphate and sodium citrate dihydrate. Both the nucleation inhibitor and the pH modifier were necessary to increase the dissolution rate and maintain supersaturation of the drug in the dissolution media. [Pg.600]

Brasile MLG, Gelens E, Vries T, Kaptein B, Kellogg R. Structural aspects of nucleation inhibitors for diastereomeric resolutions and the relationship to Dutch resolution. Angew. chem. Int. Ed. 2008 47 1287-1290. [Pg.1681]

Two nucleation processes important to many people (including some surface scientists ) occur in the formation of gallstones in human bile and kidney stones in urine. Cholesterol crystallization in bile causes the formation of gallstones. Cryotransmission microscopy (Chapter VIII) studies of human bile reveal vesicles, micelles, and potential early crystallites indicating that the cholesterol crystallization in bile is not cooperative and the true nucleation time may be much shorter than that found by standard clinical analysis by light microscopy [75]. Kidney stones often form from crystals of calcium oxalates in urine. Inhibitors can prevent nucleation and influence the solid phase and intercrystallite interactions [76, 77]. Citrate, for example, is an important physiological inhibitor to the formation of calcium renal stones. Electrokinetic studies (see Section V-6) have shown the effect of various inhibitors on the surface potential and colloidal stability of micrometer-sized dispersions of calcium oxalate crystals formed in synthetic urine [78, 79]. [Pg.338]

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural... Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...
Achieving steady-state operation in a continuous tank reactor system can be difficult. Particle nucleation phenomena and the decrease in termination rate caused by high viscosity within the particles (gel effect) can contribute to significant reactor instabilities. Variation in the level of inhibitors in the feed streams can also cause reactor control problems. Conversion oscillations have been observed with many different monomers. These oscillations often result from a limit cycle behavior of the particle nucleation mechanism. Such oscillations are difficult to tolerate in commercial systems. They can cause uneven heat loads and significant transients in free emulsifier concentration thus potentially causing flocculation and the formation of wall polymer. This problem may be one of the most difficult to handle in the development of commercial continuous processes. [Pg.10]

Recent interest has focused on acidic phosphoproteins, such as bone sialoprotein, acting as sites of nucleation. These proteins contain motifs (eg, poly-Asp and poly-Glu stretches) that bind calcium and may provide an initial scaffold for mineralization. Some macromolecules, such as certain proteoglycans and glycoproteins, can also act as inhibitors of nucleation. [Pg.550]

Thermodynamic inhibitors Antinucleants Growth modifiers Slurry additives Anti-agglomerates Methanol or glycol modify stability range of hydrates. Prevent nucleation of hydrate crystals. Control the growth of hydrate crystals. Limit the droplet size available for hydrate formation. Dispersants that remove hydrates. [Pg.162]

The usual practice for avoiding the plugging of production facilities by hydrates is to add thermodynamic inhibitors, such as methanol or glycol. A newer concept is the injection of low-dosage additives either kinetic inhibitors, which delay nucleation or prevent the growth of hydrate crystals, or hydrate dispersants, which prevent the agglomeration of hydrate particles and allow them to be transported within the flow [880,1387]. Hydrate control is discussed extensively in Chapter 13. Classes of hydrate control agents are shown in Table 11-9, and additives are shown in Table 11-10. [Pg.162]

Knowledge concerning the mechanism of hydrates formation is important in designing inhibitor systems for hydrates. The process of formation is believed to occur in two steps. The first step is a nucleation step and the second step is a growth reaction of the nucleus. Experimental results of nucleation are difficult to reproduce. Therefore, it is assumed that stochastic models would be useful in the mechanism of formation. Hydrate nucleation is an intrinsically stochastic process that involves the formation and growth of gas-water clusters to critical-sized, stable hydrate nuclei. The hydrate growth process involves the growth of stable hydrate nuclei as solid hydrates [129]. [Pg.178]

A (3 fibril formation an identifiable nucleating species has yet be isolated. Direct observation has been made difficult by the small size of the (3 peptide, which has an effective hydrodynamic radius of 4 nm [98-100], and by the apparent low abundance of nucleating species due to the low probability of their formation. Such species would be formally akin to an enzyme transition state that is usually kinetically inferred or sometimes trapped with certain kinds of inhibitor. In disaggregated, ultrafiltered (20 nm pore size) preparations, less than 1% of the molar peptide concentration is inferred to be present as seeds or nuclei determined by the kinetics of fibril formation [101]. [Pg.259]

High-pressure liquid chromatographic (HPLC) analysis performed with a chiral mobile phase (57,58) confirmed in all the conglomerate systems that the S inhibitors are selectively occluded only in the bulk of the S substrate crystals, typically in amounts of 0.5-1% (and, by symmetry, occlusion of R occurs only in R crystals). The selective adsorption causes, furthermore, a drastic decrease in the growth (and possibly nucleation) rate of the affected enantiomer, leading to efficient kinetic resolution various conglomerate systems have been resolved by this method (54). [Pg.24]

We reported in the previous papers [8, 9] that the effect of the operational factors such as temperature and solvents on the polymorphic crystallization of a thiazole derivative - 2-(3 -Cyano-4-(2-methylpropoxy)-phenyl)-4-methyl-thiazole-5-car-boxylic acid (BPT) - which is an enzyme inhibitor. In this paper, we synthesized the esters of BPT and studied the effect of the molecular structure on polymorphic nucleation systemically, and at the same time we also examined the solvent effect on the polymorphic nucleation of the ester. [Pg.125]

In gallstone patients, the nucleation of supersaturated bile requires either an excess of promoters, or a deficiency of inhibitors, of crystallisation (or both). For the past 20 years, attempts have been made to identify these pro- and antinucleating agents - but so far without consensus. Suffice to say that the promoters and inhibitors are mainly proteins and that mucous glycoprotein is particularly important - not only as a promoter of nucleation but also because it forms a gel on the surface of the gallbladder mucosa, which is believed to trap cholesterol crystals and contribute to the stasis within the gallbladder. Table 8.1 gives a list of potential promoters and inhibitors. [Pg.144]

Table 8.1 Proven and putative promoters and inhibitors of nucleation of cholesterol microcrystals in gallbladder bile. Table 8.1 Proven and putative promoters and inhibitors of nucleation of cholesterol microcrystals in gallbladder bile.

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See also in sourсe #XX -- [ Pg.338 ]

See also in sourсe #XX -- [ Pg.220 ]




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Nucleation inhibitors, design

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