Comparison of the Ability of Various Pharmaceutical Silicates to Amorphize and Enhance Dissolution of Indomethacin Upon Co-grinding

Abstract

The physical stability, dissolution rate, and solubility enhancement of indomethacin amorphized by co-grinding with 6 pharmaceutical silicates were investigated. Mixtures of indomethacin and silicates were co-ground to amorphous states at room temperature and 75% relative humidity (RH) in a rolling jar mill. The fraction of indomethacin amorphized was higher than would be expected for monolayer coverage on the silicate, suggesting additional stabilization of the amorphous drug in the mesopores of the silicate. The co-ground amorphous indomethacin was physically stable for 3 to 6 months at 40°C/75% RH. The physicochemical properties (surface area, crystallinity, presence and absence of metal ions such as Mg²⁺, Al³⁺, Ca²⁺) of the silicates affect the amorphization time, chemical stability, dissolution, and solubility.

Keywords:

• amorphization
• co-grinding
• indomethacin
• solubility
• silicate