Increasing the Dissolution Rate of a Low-Solubility Drug Through a Crystalline-Amorphous Transition: A Case Study with Indomethicin

Abstract

The purpose of this research is to further the understanding of the crystalline to amorphous phase transition (amorphization) that occurs when some crystalline drugs are dry blended with porous adsorbents. Indomethacin (IMC) and three grades of silica gel (SGs) were used in the study. Amorphization of crystalline IMC occurs rapidly during dry mixing with SG and was independent of mixing intensity and time. Extent of amorphization increases with lower ratios of IMC:SG and with decreased IMC and SG particle size. Blocking H-bonding silanol groups on SG by chemical modification reduced the extent of amorphization. IMC-SG mixtures showed improved dissolution rates over crystalline IMC, the improvement being directly related to the extent of amorphization. To preserve the improved dissolution rate, mixtures should be protected from moisture and heat. This approach holds promise as a mean of improving the dissolution rate of sparingly soluble drugs such as IMC.

Keywords:

• amorphization
• quantitative analysis
• phase transition
• differential scanning calorimetry
• dissolution
• X-ray powder diffractometry
• indomethacin
• silica gel
• amorphous
• crystalline
• hydrogen bonding