Effect of wet milling process on the solid state of Indomethacin and Simvastatin.

Abstract

The aim of this study was to investigate the effect of wet milling on the solid state of indomethacin (IMC) and simvastatin (SIM). Wet milling was performed using high pressure homogenization (HPH). Polyvinylpyrrolidone-K25 (PVP) and poloxamer 407 (P407) were used as suspension stabilizers. Samples were characterized before and after wet milling using particle size analyzer, scanning electron microscopy (SEM), infrared (IR) spectroscopy and modulated temperature differential scanning calorimetry (MTDSC) techniques. After wet milling of IMC, physical appearance and IR spectra indicated surface amorphization; however, the solid state of SIM remained unaffected. MTDSC could not detect surface amorphization in IMC, suggesting that if present, it was only at very low levels. These results are in contradiction to the previous reports where dry milling of IMC and SIM resulted in amorphization of crystalline particles. Moreover, cryogrinding of IMC in the absence of water resulted in an amorphous form while presence of water using the same cryogrinding conditions resulted in a solid state similar to that obtained after wet milling. These results signify the role of water in inhibiting the amorphization during wet milling of crystalline drugs.