Enhancement of Valsartan Oral Bioavailability by Preparing a Microwave-Irradiated Inclusion Complex with Sulfobutyl Ether β-Cyclodextrin Using a Central Composite Face Design for Optimising Process Parameters

The purpose of the study is to investigate the influence of sulfobutyl ether beta-cyclodextrin (SBE7-beta-CD) on the bioavailability of valsartan. Phase solubility investigations showed an A(L) type curve. The estimated apparent stability constant for valsartan SBE7-beta-CD is 427 +/- 0.32 M-1. Inclusion complexes of valsartan SBE7-beta-CD in equal molar ratio were prepared by microwave irradiation technique. The process parameters were optimised with a central composite face design. Response surface graphs and contour plots showed how process factors affected drug content. The inclusion complexes prepared by optimising process variables are characterised. The DSC and X-ray diffraction confirm the formation of inclusion complexes and the drug's transition from a crystalline to an amorphous state. FTIR suggests hydrogen bonding between valsartan and SBE7-beta-CD. SEM showed changes in drug morphology and shape. The dissolution rate of the prepared SBE7-beta-CD complex using microwave irradiation was 2.85 times that of pure valsartan. The inclusion complex was formulated into tablet dosage forms F-1 to F-4. Furthermore, oral bioavailability studies in rats with tablet formulation F-3 were carried out and compared to the marketed Diovan (R) tablet as a reference standard. The F-3 tablet formulation exhibited significantly higher values of AUC(0-infinity) and C-max than the reference. Finally, the microwave-irradiated valsartan SBE7-beta-CD inclusion complex converted into tablet dosage form may be a promising approach to increasing valsartan oral bioavailability.