Characterization of complex coacervates of some tricyclic antidepressants and evaluation of their potential for enhancing transdermal flux

Complex coacervation is the separation of an aqueous mixture of oppositely charged ions into a dense coacervate oil phase, rich in ionic complex, and a dilute equilibrium phase. Coacervation was investigated between cationic tricyclic antidepressants (amitriptyline, imipramine and doxepin) and counter-ions of anionic bile salts sodium cholate (NaC) and sodium deoxycholate (NaD), and the surfactant sodium lauryl sulfate (SLS). Systems were analyzed by microscopy, HPLC, Karl Fischer titration, thermogravimetric analysis and particle size analysis. Two systems were selected to investigate the potential of this formulation for enhancing transdermal flux of charged species - amitriptyline (AMI) with NaD, which separates into two distinct phases, and AMI with SLS which remains as a sol. Octanol/vehicle partition coefficients were determined and the AMI:NaD coacervate produced an 18-fold increase and AMI:SLS 22-fold compared with aqueous solution. Permeation experiments were performed using human epidermal membrane with an aqueous receptor and the flux from a 0.025 M aqueous solution which is above the critical micelle concentration (0.015 M) was 3.0 +/- 0.54 mu g/cm(2)/h (S.E.M., n = 10). The flux from an AMI:NaD coacervate donor was 6.6 +/- 0.71 mu g/cm(2)/h (S.E.M., n = 8), which represents a significant 2.2-fold increase (t-test, P = 0.01). The AMI:SLS system, however, reduced the flux compared with the aqueous solution. Permeation studies were repeated using silastic membrane to exclude simple enhancing effects of the counterions and similar differences in flux were obtained indicating that the changes were due to the formulation. The results indicate that the increased lipophilicity of the coacervate oil phase can increase the transdermal flux of charged species.