SELF-ASSOCIATION OF PHENOTHIAZINE DRUGS - INFLUENCE OF THE COUNTERIONON THE MODE OF ASSOCIATION

The association characteristics of the phenothiazine drug trimeprazine tartrate in water and aqueous electrolyte solution have been examined using static and dynamic light scattering techniques and compared wit h those reported for the structurally related drug promethazine hydroc hloride, to identify differences in association pattern arising from d ifferences in the counterions of the two drugs. The association of tri meprazine tartrate was micellar in water and the the presence of added electrolyte. A progressive increase of aggregation number and micella r radius was observed with increase of sodium chloride concentration o ver the range 0.05 to 0.60 M NaCl. This behavior is in contrast to tha t of promethazine hydrochloride which exhibits continuous association above the critical concentration in electrolyte of concentrations grea ter than or equal to 0.2 M NaCl. Moreover, static light scattering cur ves for trimeprazine tartrate showed a single discontinuity correspond ing to the onset of micellization, whereas the association behavior of promethazine hydrochloride (and other phenothiazine drugs with chlori de counterions), in water and dilute electrolyte (0.05-0.1 M NaCl), is complex, with discontinuities in solution properties at several criti cal concentrations. The results of this study highlight the influence of the counterion on the association characteristics of this class of amphiphile. (C) 1996 Academic Press, Inc.