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

Abstract

Purpose: 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.

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

Results: 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.

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

Keywords: candesartan cilexetil (CDST); dissolution; mesoporous silica; sodium carbonate; solvent evaporation method; stability.