Correlating the phase behaviour of semi-synthetic antibiotics and their precursors in water+1-butanol mixtures

In this contribution we present experimental data on the solubilities of two semi-synthetic antibiotics (amoxicillin (amox), ampicillin (ampi)) and their precursors (d-phenylglycine (PG), d-(p-hydroxy) phenylglycine (HPG), 6-aminopenicillanic acid (APA)) in pure water at varying temperature and pH, and in water+1-butanol mixtures at 298 K. The solubilities in water as a function of the temperature and the pH are described successfully with the help of a simplified perturbed hard sphere theory (SPHST) [M.K. Khoshkbarchi, J.H. Vera, Ind. Eng. Chem. Res., 35 (1996) 4319-4327.]. The solubilities in the mixed solvent system are described reasonable with the gE-model proposed by Gude et al. [M.T. Gude, L.A.M. van der Wielen, K.Ch.A.M. Luyben, Fluid Phase Equilibria, 116 (1996) 110-117; M.T. Gude, H.H.J. Meeuwissen, L.A.M. van der Wielen, K.Ch.A.M. Luyben, Ind. Eng. Chem. Res., 35 (1996) 4700-4712.]. This model, based on an excess-solubility approach, contains only one adjustable interaction parameter which correlates with the hydrophobicity in a similar manner as it was observed for amino acids. However, the increasing relative solubility in the aqueous phase, which was observed for the systems containing amox and ampi, cannot be represented by this model. However, when the combinatorial term of the Gude model was extended, a good representation of this kind of phase behaviour is obtained as well.