Sodium deoxycholate mediated enhanced solubilization and stability of hydrophobic drug Clozapine in pluronic micelles

In this report, the solubilization behaviour of a hydrophobic drug Clozapine (CLZ) in micellar suspensions of pluronics having different hydrophilic lipophilic balance (HLB) ratios viz. P84, F127 and F108 in the absence and presence of bile salt sodium deoxycholate (SDC) has been studied. UV-Vis spectroscopy has been exploited to determine the solubilization capacity of the investigated micellar systems in terms of drug loading efficiency, average number of drug molecules solubilized per micelle (n_s), partition coefficient (P) and standard free energy of solubilization (∆G^°). The morphological and structural changes taking place in pluronics in different concentration regimes of SDC and with the addition of drug CLZ has been explored using dynamic light scattering (DLS) and small angle neutron scattering (SANS) measurements. The SANS results revealed that aggregation behaviour of pluronic-SDC mixed micelles gets improved in the presence of drug. The micropolarity measurements have been performed to shed light on the locus of solubilization of the drug in pure and mixed micellar systems. The compatibility between CLZ and drug carriers (pluronics and SDC) was confirmed using powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) techniques. Among the investigated systems, P84-SDC mixed system was found to be highly efficient for CLZ loading. The long term stability data indicated that CLZ loaded P84-SDC mixed micellar formulation remained stable for 3months at room temperature. Further, it was revealed that the CLZ loaded P84-SDC mixed micelles are converted into CLZ loaded pure P84 micelles at 30-fold dilutions which remain stable up to 48-fold dilutions. The results from the present studies suggest that P84-SDC mixed micelles can serve as suitable delivery vehicles for hydrophobic drug CLZ.