Formulation and characterization of solid dispersion adsorbate of Candesartan Cilexetil: in vitro dissolution and in vivo performance

Introduction Candesartan Cilexetil (CC) is a non-peptide angiotensin II type 1 receptor antagonist widely used in the treatment of hypertension. However, CC has poor aqueous solubility (0.006 ± 0.002 mg/mL), low oral bioavailability (15%) and undergoes significant first-pass metabolism. Methods Candesartan Cilexetil Solid Dispersion adsorbate (CC-SDAs) was formulated by the fusion method, employing polyethylene glycol (PEG) 4000 as a hydrophilic carrier and Neusilin® US2 as an adsorbent, to improve the solubility, dissolution, and oral bioavailability of CC. The formulation was optimized using a 3 2 factorial design. Results and Discussion The optimized SDA formulation exhibited the following properties: Carr’s index (9.86 ± 0.09%), Hausner’s ratio (1.10 ± 0.16) and angle of repose (26.00 ± 0.19°), which shows improved flow property. DSC and XRD studies confirmed the conversion of the crystalline drug into an amorphous form. The optimized SDA formulation achieved %CDR of 90.41 ± 0.95% at Q30 min, demonstrating a marked improvement in in vitro dissolution compared to the pure drug (%CDR of 57.20 ± 3.78% at Q30 min). Furthermore, in vivo pharmacokinetic studies revealed a 2.02-fold enhanced oral bioavailability of CC from the SDA formulation compared to the CC suspension. Therefore, the SDA technique proves to be a promising approach for enhancing the solubility and dissolution of poorly water-soluble drugs.