Development of Candesartan Cilexetil-sodium Carbonate Anhydrate-mesoporous Silica Solid Dispersion in Polymer-free...

Candesartan cilexetil (CDST) is used to treat hypertension; the drug belongs to the Biopharmaceutics Classification System (BCS class II) due to its low solubility in aqueous solutions. The commercial product, Atacand®Tab, contains 16 mg of CDST in a small tablet weighing approximately 130 mg. This study developed a polymer-free system by using a CDST solid dispersion (SD) of sodium carbonate anhydrate and mesoporous silica.

The SD formulation was developed to ensure solubilization and stability of CDST using a solvent evaporation method.

The dissolution (%) of CDST in the optimal formulation (SD1) at 60 min in pH1.2 medium, pH4.0 buffer, distilled water (DW), and pH6.8 buffer without polysorbate 20 increased by 35.2-, 45.5-, 34.4-, and 28.1-fold compared to that of Atacand®Tab and by 63.4-, 37.5-, 1.7-, and 46.9-fold, respectively, compared to the physical mixture (PM1). The dissolution of SD1 formulation was over 98% in DW and pH6.8 buffer after 60 min. The physicochemical properties of the SD1 formulation changed the melting point, drug-excipient interaction, and crystallinity of CDST. Additionally, the stability of SD1 formulation for 12 months was secured.

The SD1 formulation improved the dissolution of CDST and secured stability by changes in its physicochemical properties.