Study of the cloud point of an amphiphilic antidepressant drug: Influence of surfactants, polymers, and non-electrolytes

The clouding phenomenon has been studied in an amphiphilic antidepressant drug (amitriptyline, AMT) solution prepared in 10 mM sodium phosphate (SP) buffer in the presence of various additives. The pH variation has also been carried out in the solution containing a fixed amount of the drug (50mM) and various surfactants (sodium dodecylsulfate, SDS, 5mM, cetylpyridinium bromide, CPB, 0.5mM, and t-octylphenoxypolyethoxyethanol, TX-100, 2 mM). Cloud point (CP) was found to decrease with increasing pH with or without surfactants. However, when surfactants were added to 50 mM AMT solutions at fixed pH (6.7), the CP behavior was found to vary according to the ionic nature of the surfactant. Similarly, with polyether type nonionic surfactants (Brij 35, TX-100, Tween 20, Tween 40, Tween 60, Tween 80) the CP was found to increase more distinctly with the surfactant having lower oxyethylene chains (i.e., TX-100). Urea and alkylureas were found to decrease the CP, which was found to be dependent upon the number of methyl groups present in the urea molecules. Contrary to this, thioureas increased the CP slightly. However, the presence of methyl group(s) has similar effect as in alkylureas. The effect of amino acids on CP of AMT solution depended upon their acidic/basic as well as polar/non-polar characteristics. All the sugars caused a decrease in CP. However, the effect of polymers on CP was found to be dependent upon the number of units present in a particular polymer of polyvinylpyrrolidone (PVP) category. The overall behavior can be interpreted in terms of variations in drug-aggregate morphology as well as modifications in the background solvents. (c) 2006 Elsevier B.V. All rights reserved.