Structural evolution is tracked as a charged surfactant, cetyltrimethylammonium chloride (CTAC), is titrated into a solution of oppositely charged polyelectrolyte, sodium poly(styrenesulfonate), to form polyelectrolyte-surfactant complexes. At surfactant-to-polymer molar charge ratio [r] less than 0.5, small-angle neutron scattering of the soluble complexes reveals bound spherical CTAC micelles of radii 21-24 Å, slightly less than for pure CTAC. At such small [r], the number of spherical micelles per chain grows with [r] but never becomes large (<2). At [r] ∼ 0.5, if salt concentration is low (<100 mM), cylindrical micelles of radii 20-22 Å and aspect ratio at least 5:1 replace the spherical micelles. Irrespective of salt concentration, at [r] ∼ 0.7 precipitation occurs, with X-ray scattering revealing CTAC arranged into hexagonally close-packed cylinders. At even higher [r], the hexagonal phase transforms into the Pm3n cubic phase. Raising ionic strength diminishes NaPSS-CTAC attraction, delaying onset of insolubility and disrupting precipitate order.

In a recent food effect clinical study, the authors concluded that a meal consisting of ≥500 kcal, regardless of fat content, produced the maximal bioavailability for ziprasidone. Using GastroPlus™, a commercially available pharmacokinetic simulation software, a semiphysiological model-a kind of physiologically based pharmacokinetic (PBPK) absorption model-was developed that could predict the concentration-time profiles when ziprasidone was administered with any one of the five test meals or fasting. Ziprasidone intravenous pharmacokinetics and oral absorption permeability were determined from clinical studies following the intravenous and duodenal infusion of ziprasidone to volunteers. From the detailed dietary information of each meal provided in the previously published food effect study, the stomach pH, volume, and gastric emptying could be predicted. Incorporating these meal-specific parameters into the model improved the predictions beyond the default fed/fasted parameters commonly used in the software. Compared to the default models, the improved models resulted in an improved prediction of the average ziprasidone concentration-time profile for each meal. Using this type of semiphysiological absorption model, we have shown that the dietary contents of the meals should be taken into account to predict food effects for ziprasidone and perhaps other BCS class I or II compounds.