SYNTHESIS AND EVALUATION OF OLMESARTAN MEDOXOMIL COMPLEX WITH SBE7 Î²-CD FOR ENHANCED DISSOLUTION AND BIOAVAILABILITY
Keywords:Complexation, Molecular modelling, Relative bioavailability, Olmesartan medoxomil, Nil
Objective: Olmesartan is a BCS class II anti-hypertensive drug with limitations of low aqueous solubility and bioavailability. ÂÂPresent work was designed to use complexation as an approach to explore the ability of modified cyclodextrin such as sulphobutyl ether7 Î²-cyclodextrin (SBE7Î²-CD) to develop an inclusion complex with poorly soluble olmesartan medoxomil (OLM) for improving its dissolution rate and relative bioavailability.
Methods: Inclusion complexes were prepared by different techniques of physical mixing, kneading and lyophilisation. Prepared complexes were characterized by differential scanning calorimetry (DSC), powder x-ray diffractometry (X-RPD), proton nuclear magnetic spectroscopy (1H NMR) and fourier transforms infrared spectroscopy (FT-IR). Molecular interaction and encapsulation in an inclusion complex at the molecular level were considered using docking chemistry.
Results: Phase solubility analysis revealed 13 fold increase in aqueous solubility with stability constant Ks=249 Mâˆ’1at 1:1 stoichiometry of complexation. DSC and XPRD confirmed the reduction of crystallinity in complexes with improved solubility. 1H NMR and FT-IR studies depicted the interaction among functional groups with varied hydrogen shifts confirmed by molecular modelling. Dissolution studies of complexes have shown an improved dissolution rate when compared to plain OLM. Pharmacokinetic profile of OLM/SBE7Î²-CD has shown a significant enhancement in the relative bioavailability.
Conclusion: SBE7Î²-CD may be successfully used as a carrier for the oral administration of OLM with enhanced bioavailability subjected to future scale up.
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