Precipitation inhibition

With preformed ACP at ratios of only one PL molecule per 30-50 Ca atoms, phosphatidyl serine markedly delays HA crystal formation. When phosphatidyl serine is present during ACP precipitation, inhibition of conversion to HA is less pronounced, but crystal habit and aggregation are greatly altered resulting in stacks of thin, membrane-like sheets approximately 3—42 A thick. Phosphatidyl serine... 

Acidic polypeptides which inhibit the precipitation of calcium oxalate in urine contain gla residues. Other precipitating-inhibiting proteins found in saliva which are rich in tyrosine and proline residues have been discussed in Section 62.1.3.4.8. 

Liu, R., Qu, J., Xia, S. et al. (2007a) Silicate hindering in situ formed ferric hydroxide precipitation inhibiting arsenic removal from water. Environmental Engineering Science, 24(5), 707-15. 

In the next section, we consider what is really happening at the atomistic scale, namely dissolution and precipitation. Inhibition of grain growth by solid-phase inclusions has been observed for MgO additions to AI2O3 and for CaO additions to Th02. 

Figure 3.22. Precipitation inhibition of calcium carbonate by polycarboxylates as a function of temperature and soda concentration (3.04 X 10 mold calcium ions) (1) 105 mg/1 polycar-boxylate (2) 210 mg/1 polycarboxylate (18)...

Although solvent-shift method enjoys simplicity and versatility in selection of the polymer, the outcome of this study is somewhat questionable as the organic solvent may interfere with precipitation kinetics and thermodynamics, and may not reflect amorphous solid system. In addition, supersaturation or precipitation inhibition potential of specific polymers is highly concentration dependent. Since local in vivo drug-polymer concentrations are difficult to predict, it is thus challenging to define suitable biorelevant polymer concentrations for in vitro experiments. 

Petrusevska M, Urleb U, Petemel L (2013) Evaluation of a high-throughput screening method for the detection of the exdpient-mediated precipitation inhibition of poorly soluble drugs. Assay Dmg Dev Technol 11 117-129... 

As Fig. 9.10 shows, the microcentrifuge test is also used (1) to quantify precipitation inhibition for compounds that rapidly crystallize and (2) to compare dissolution rates for SDDs of more lipophilic compounds, which tend to dissolve more slowly as particle size increases during process scale-up. A simulated gastric exposure step before dissolution in simulated intestinal media can also be added. This option is useful when evaluating weakly basic compounds that have pH-dependent solubility (Mathias et al. 2013). 

Fig. 9.10 Representative drug properties and data for a wide range of SDD formulations from a solubilization technology map (a), showing how the microcentrifuge test can be used to qutmtify precipitation inhibition (b), and to show negative impacts on dissolution rate for properties such as increased particle size (c)...

Since transport across the biological membrane of weak bases will be more pronounced in the small intestine (uptake of the unionized form), sufficient precipitation inhibition (polymer) is required upon transfer of the supersaturated solution to the intestine. Therefore, one cannot rely on dissolution studies at constant acidic pH to predict the performance of formulations of weak bases in vivo (Miller et al. 2007). For instance. Six et al. (2005) observed a discrepancy between the results of in vitro dissolution tests in acidic medium and in vivo absorption for four solid dispersions of ITR faster release and increased supersaturation in acidic medium correlated with lower bioavailability. Presumably, this effect can be explained by differences in crystallization rate upon transfer to the small intestine (increased driving force for precipitation in case of higher supersaturation). Thus, it is crucial to simulate the GI pH shift during supersaturation dissolution testing of weak bases to evaluate whether supersaturation is maintained in the small intestine. 

As a result of change in pressure, composition, and temperature to a lesser degree, the micellar size shown in Figs. 5.10 and 5.11 may change (Nielsen, et al., 1994). The equilibrium between the precipitated phase and the bulk-liquid phase will be effected as a result of the micellar size. This is one main reason that cubic equations such as the PR-EOS, which have been used so successfully in vapor-liquid equilibria, may not be suitable for asphaltene-precipitation and asphaltene-precipitation inhibition calculations. This point will become clear later. 

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