title: Enhanced solubility and intestinal absorption of candesartan cilexetil solid dispersions using everted rat intestinal sacs.
abstract: OBJECTIVE
  Candesartan cilexetil (CAN) is a poor aqueous soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These key factors are responsible for its incomplete intestinal absorption.
  
  
  METHODS
  In this study, we investigated to enhance the absorption of CAN by improving its solubility and inhibiting intestinal P-gp activity. A phase solubility method was used to evaluate the aqueous solubility of CAN in PVP K30 (0.2-2%). Gibbs free energy [Formula: see text] values were all negative. Solubility was enhanced by the freeze drying technique. The in vitro dissolution was evaluated using the USP paddle method. The interaction between drug and carrier was evaluated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) studies. Naringin was selected as P-gp inhibitor. Absorption studies were performed using the everted gut sac model from rat jejunum. The drug analysis was performed by HPLC.
  
  
  RESULTS
  FTIR spectra revealed no interaction between drug and PVP K30. From XRD and DSC data, CAN was in the amorphous form, which explains the cumulative release of drug from its prepared systems. We noticed an enhancement of CAN absorption by improving its solubility and inhibiting the P-gp activity. The significant results (p < 0.05) were obtained for freeze dried solid dispersions in the presence of P-gp inhibitor than without naringin (15 mg/kg) with an absorption enhancement of 8-fold.
  
  
  CONCLUSIONS
  Naringin, a natural flavonoid, has no undesirable side effects. Therefore, it could be employed as an excipient in the form of solid dispersions to increase CAN intestinal absorption and its oral bioavailability.
authors: Department of Pharmacology, KLE University, Belgaum - Karnataka, India.
authors: S
authors: S
authors: Gurunath
authors: Department of Pharmaceutics, KLE University, Belgaum - Karnataka, India.
authors: Baswaraj K
authors: BK
authors: Nanjwade
authors: Department of Pharmacology, KLE University, Belgaum - Karnataka, India.
authors: P A
authors: PA
authors: Patila
keywords: Candesartan cilexetil; Flavonoid; Intestinal absorption; Naringin; P-gp inhibitor