Adsorption and Micellization Behavior of Mixtures of Amphiphilic Drugs with Small Amounts of Bile Salts

Abstract

AbstractBile acid salts are the most important biological surfactant-like molecules. These compounds play an active role in the cholesterol and lipid solubilization. They are also used as drug carriers. The salts give anionic amphiphilic moiety in aqueous solution and will interact strongly when mixed with cationic amphiphiles. With this aim we have investigated mixed systems of three bile acid salts (sodium cholate (NaC), sodium deoxycholate (NaDC) and sodium taurocholate (NaTC)) with two cationic drugs (adiphenine hydrochloride (ADP) and clomipramine hydrochloride (CLP)) by surface tension measurements. It was found that the two components mix nonideally, i.e., the cmc values of the mixtures decrease with the stoichiometric mole fraction (α1) of bile salts and are lower than cmc* values (cmc at ideal mixing condition). The interaction parameters, βm and βσ, come out to be negative and large in magnitude which is obvious from the fact that the two components are of opposite charge and would experience attractive interactions. The results suggest that the contribution of bile salts in the mixed micelles (X1m) is greater than both the α1 and X1id (the contribution in ideal mixing condition). These components also form mixed interface where the contribution of bile salts is more than α1 (i.e., X1σ > α1). The minimum area occupied by a monomer decreases with increase in the content of bile salts in the solution. This confirms that the opposite charges on the two components decrease the repulsion among the head groups. All the evaluated thermodynamic parameters (i.e., ΔG0m, ΔGex, ΔG°ads and Gmin) support the above explanations.