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in precipitation, thereby demonstrating API:IP interactions are responsible for the phase formation (phase change). As a general trend, the IPs that caused precipitation are higher MW, more hydrophobic, and of a stronger acidic form compared to IPs that did not cause precipitation. These effects can be explained by the fact that more strongly hydrophobic IPs produce more hydrophobic API:IP com› plexes, and that IPs that ionically interact more strongly with the APis produce stronger API:IP complexes. In another method of quantification, IPs that caused precipitation have higher c Log P, and have acid forms with lower pKa. All IPs that caused precipitation have c Log P greater than 0.11; however one IP tested, sodium hexanoate, has a c Log P of 2.01 but did not cause precipitation. The acid form of sodium hexanoate is a weak acid with a pKa of 4.88. The comparatively poor ability of the acid form to ionize in solution limits its ability to ion pair with the API, since deprotonation of the acid is required for the required strong electrostatic interaction with the amine on the APL These results demonstrate that high IP hydrophobicity is a neces› sary, but not sufficient criteria of precipitating the APis. Both hydrophobicity and strong ionic interactions are necessary. 

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while - details no solids formed. In the organic dissolution test, ++ details complete dissolution, while + details non› 

complete dissolution. In the re-precipitation test, + details re-precipitation observed, and - details no re› 

precipitation observed. 

[0083] Out of the fifteen IPs tested with gentamycin, nine IPs resulted in the formation of precipitates; six IPs did not produce an observable precipitate (Tables 1 and 3). 

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while - details no solids formed. In the organic dissolution test, ++ details complete dissolution, while + details non› 

complete dissolution. In the reprecipitation test, + details reprecipitation observed, and - details no reprecipi› 

tation observed. 

[0084] After successfully identifying water-insoluble API: IP complexes, it was determined whether these new salt forms could be dissolved in THF for NC processing. Pellets formed from the previous step were incubated with THF at a 1 x volume equal to the starting volume of API in water. Of the eleven API:IP complexes tested, all complexes, except sodium decanoate and sodium deoxycholate, dissolved in THF. The IP sodium octanesulfonate, which has a hydro› phobic eight carbon chain pendant group, was sufficient for API:IP dissolution into THF, whereas sodium decanoate, which has a hydrophobic nine carbon chain pendant group, was not. The pKa of the acid form of sodium octanesulfonate is -0.40, while that of sodium decanoate is 4.0; this effect of pKa highlights differences in the ability of these two IPs to charge interact with the APis. Thus, although sodium decanoate is a more hydrophobic IP with a Log P of 2.01, sodium octanesulfonate with a Log P of 0.85 is a better IP agent due to its greater ability to ionically complex with APis. As a control, APis prepared without IP complexation were not soluble in THF, highlighting that association with hydrophobic IPs is necessary for solubility in organic sol› vents. These results demonstrated that IP reagents that are more hydrophobic are not necessarily better for API:IP complex formation, and IPs with lower acid form pKa can be better at forming hydrophobic salts. 

[0085] In the FNP process, API:IP complexes dissolved in organic solvents must rapidly precipitate when mixed against the water antisolvent. To assess whether the nine remaining API:IP salt complexes would behave accordingly, complexes dissolved from the previous step were rapidly mixed and diluted tenfold into water. 

[0086] The results of the tests are shown in FIG. 4, where the axes are the pKa of the IP agent and the calculated Log P of the compounds. Four of the IPs tested resulted in no observable precipitation upon mixing (diamonds in FIG. 4). Four of the IPs tested resulted in rapid precipitation and successful NC formation (squares); those IPs were sodium oleate (OA), pamoic acid disodium salt (PA), sodium dode› cylbenzene sulfonate (DBS), and sodium dodecyl sulfate (SDS). The IPs that failed to produce precipitates at this stage were the least hydrophobic among the group, with Log 

