Study of phospholipid-induced phase-separation in amphiphilic drugs

Phase separation of five amphiphilic drugs in 10 mM phosphate buffer with added phospholipids has been studied. The drugs used are tricyclic antidepressants (amitriptyline hydrochloride, imipramine hydrochloride, and clomipramine hydrochloride) and phenothiazines (promethazine hydrochloride and promazine hydrochloride). Depending on the nature and structure of studied compounds, the phospholipids caused different effects on the clouding behavior. Cardiolipin decreased the cloud point for all drugs. With amitriptyline, all the additives lowered the cloud points, whereas the clomipramine showed opposite tendency. Imipramine and promethazine led to similar extremal behaviour of cloud point, although promazine, which is structurally similar to promethazine, did not show the same tendency. Thermodynamic analysis of the experimental data suggested that the process of clouding is entropically driven.