LAUSR

Abstract A fixed-dose combination of Candesartan cilexetil (CAN) and Hydrochlorothiazide (HCTZ) is commonly used for the management of hypertension. CAN (BCS class II) and HCTZ (BCS class IV) suffer from inadequate oral bioavailability. Herein, the study aims to design a self-nano emulsifying drug delivery system (SNEDDS) containing a fixed-dose combination of both drugs to enhance their dissolution rate and hence oral bioavailability. Formulation of fixed-dose combination-loaded SNEDDS was carried out using various oils, surfactants, and co-surfactants, and phase diagrams were plotted using different ratios. In vitro characterizations of drug-loaded SNEDDS were achieved through optical clarity, emulsification efficiency, globule size, morphology, viscosity, drug-excipient interactions, and thermodynamic stability. The in vitro release profiles of both drugs from optimized SNEDDS and their in vivo biological activity compared to free drugs and a marketed product were studied. Optimized formulas showed a percentage transmittance greater than 90%, emulsification time less than 1 min, globule size in the nanometric range of (27–69 nm), and superior thermodynamic stability after dilution and at different pH values. Fourier Transform Infra-Red (FTIR) studies demonstrated the absence of physicochemical interactions between drugs and additives. Transmission electron microscopy (TEM) images revealed spherical, non-aggregated globules that were consistent with the results of size analysis. Optimized SNEDDS showed a better release profile for both drugs than those of pure drugs and marketed products and therefore, higher biological activity was observed in hypertensive rats. SNEDDS can be used as a promising drug delivery carrier for improvement of the dissolution rate and the pharmacodynamic activity of the antihypertensive fixed-dose combination of CAN/HCTZ.