Anomalous solution behavior of 2-palmitate esters of lincomycin and clindamycin

The aqueous solubilities of lincomycin and clindamycin 2-palmitate esters are compared. Clindamycin 2-palmitate hydrochloride has an unusually high solubility at 25 degrees, which is due to micelle formation. Both compounds are surface active with relatively low critical micelle concentrations. However, since the Krafft point of lincomycin palmitate is approximately 43 degrees, it does not form micelles below that temperature and appears to be quite insoluble until heated above 43 degrees. The experimental monomeric solubilities of the two compounds agree with calculations based on group contributions to lipophilicity. Clindamycin 2-palmitate hydrochloride solutions are quite sensitive to ions, being salted out as unprotonated base in the form of oily droplets. Salting out correlates well with anionic strength, which is quite constant for the various salts studied. A viscosity maximum occurs with increasing salt addition, with the peaks of the different salts occurring at the same anionic strengths.