Solubilization study of antihypertensive drug Irbesartan in EO-PO based polymeric nanomicelle and optimization of its release behavior

Abstract

Irbesartan (IRB) has low bioavailability due to its poor aqueous solubility and dissolution rate, thereby making it imperative to understand their absorption behavior. The present research work is aimed for improvement of solubilization of IRB, by investigating the effect of molecular characteristics/hydrophobicity of Pluronic® copolymers; P84 and F108 micelles with and without added salt (NaCl). The solubility of IRB was increased with copolymer concentration. Effect of added salt (NaCl) showed completely opposite behavior for both the copolymers; where F108 with NaCl has adverse effect on IRB solubilization and considerable decrease was observed. The micelle/water partition coefficient and the standard free energy change (∆G◦) were also evaluated from thermodynamic view point. The in vitro release kinetics of IRB drug was carried out for 1% P84 with and without 1 M NaCl and compared with its release in water. It was found that P84/NaCl reduces the release rate more efficiently for IRB compared to other systems. There are few reports about the solubilization improvement of IRB; but this is the first time where the study of Pluronic® micelle carried out for IRB solubilization with varying solvent condition as per best of our knowledge. This information can be useful to understand the solubilization behaviour of Pluronic® copolymers available in varieties of molecular weights and can be used to identify possible solvent condition for newer applications of Pluronic® copolymers in pharmaceutical field.