Effect of Soluplus® on γ-cyclodextrin solubilization of irbesartan and candesartan and their nanoaggregates formation

Abstract

The poor aqueous solubility of irbesartan (IRB) and candesartan cilexetil (CAC) may hamper their bioavailability when orally or topically administered. Among several attempts, the promising nanoaggregate formation by gamma-cyclodextrin (gamma CD) complexation of drugs in aqueous solution with or without water-soluble polymers was investigated. According to phase solubility studies, Soluplus (R) showed the highest complexation efficiency (CE) of drug/gamma CD complexes among the polymers tested. The aqueous solubility of IRB and CAC was markedly increased as a function of Soluplus(R) concentrations. The binary drug/gamma CD and ternary drug/gamma CD/Soluplus(R) complex formations were supported and confirmed by solid-state characterizations, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FT-IR) spectroscopy. The true inclusion mode was also proved by proton nuclear magnetic resonance (H-1-NMR) spectroscopy. The nanoaggregate size and morphology of binary and ternary systems were observed using dynamic light scattering (DLS), and transmission electron microscopy (TEM) techniques. The size of these nanocarriers depends on the concentration of Soluplus(R). The use of Soluplus(R) could significantly enhance drug solubility and stabilize complex nanoaggregates, which could be a prospective platform for drug delivery systems.