Comparative solubilization of Gliclazide in solutions of two anionic micelles with asymmetrical hydrophobic chain length: An experimental and theoretical analysis

Abstract

Gliclazide (GCL) is used widely for reducing hyperglycemia in diabetic patients. It has poor solubility which leads to low oral bioavailability because of significant first-pass metabolism. In this work, we have employed two anionic micellar solutions of different hydrophobic chain lengths to solubilize GCL. They are sodiumtetradecyl sulfate (STS) and sodiumdodecyl sulfate (SDS). Our results reveal that longer hydrophobic chain was better suited for solubilizing GCL. The drug-surfactant interactions were assessed through FT-IR, conductivity, UV-Spectrophotometry, dynamic light scattering and antioxidant study. The results were compared with computational studies. There was negative free energy of micellization and positive entropy of micellization GCL + STS and GCL + SDS systems predicting spontaneity of the processes as calculated from the conductivity experiments. From the UV spectral studies, using Benesi-Hildebrand (B-H) equation, the binding constants demonstrated higher value for GCL + STS (0.286 M−1) compared to GCL + SDS (0.0231 M−1). The antioxidant properties of the above two combinations show that STS (93.14 %) has higher radical scavenging activity (RSA %) compared to SDS (77.45 %). Protein binding studies too indicated higher binding constant for STS than SDS with the drug. The docking model also supported the above findings. The longer hydrophobic chain length facilitated the solubilization of GCL with improved properties. This study offers a novel drug formulation for widely used drug GCL.