Bile Salts Aggregation Behavior at Various Temperatures under the Influence of Amphiphilic Drug Imipramine Hydrochloride in Aqueous Medium

Abstract

The aim of this investigation is the characterization of interaction of different bile salts – sodium cholate (NaC), sodium deoxycholate (NaDC) and sodium taurocholate (NaTC) with amphiphilic drug imipramine hydrochloride (IMP) because the bioavailability of lipophilic drugs following oral administration strongly depends on the presence of food components. These bile salts improve the bioavailability of poorly absorbable drugs by lowering the surface tension of the gastrointestinal fluid or by solubilization. The interactions in the binary systems (drug and bile salts) were studied by determining various physicochemical parameters like critical micelle concentration (cmc), ideal cmc (cmc^id), counterion dissociation (g), standard Gibbs free energy (ΔG_m⁰), enthalpy (ΔH_m⁰), and entropy of micellization (ΔS_m⁰), micellar mole fractions of bile salt (X₁^Rub, X₁^M, X₁^Rod), micellar mole fraction of bile salt in ideal state (X₁^id), interaction parameter (β), activity coefficients (f₁, f₂), and excess free energy of mixing (ΔG_ex) of the mixed micelles using Clint's, Rubingh's, Motomura's and Rodenas's theories for mixed micellar systems. All the results point out synergism and attractive interactions in the mixed systems of drug and bile salts. NaDC is more effective in reducing the cmc of drug IMP as compared to NaC and NaTC because it binds strongly to the positively charged drug ions and reduces the head group area more in comparison to other. This study will give insight into the selection of drugs in different applications as their properties get modified by interaction with bile salts, thus influencing their solution behavior which, in turn, modifying the phase-forming behavior, microemulsion, clouding phenomenon, besides solubilization. The modification of solubilization ability in a medium can be exploited for the purpose of selective encapsulation and release.