Microcosmic mechanisms of amorphous indomethacin crystallization and the influence of nano-coating on crystallization

Amorphous drugs have higher solubility, better oral bioavailability and are easier to be absorbed than their crystalline counterparts.  However, the amorphous drugs, with weak stability, are so easy to crystallize that they will lose the original advantages.  Polarization microscope, scanning electron microscope, differential scanning calorimetry, X-ray diffractomer and Raman spectroscopy were used to study the microcosmic crystallization mechanisms of amorphous indometacin and the performance of the drug crystals.  The results showed that the growth rate of amorphous indometacin crystals at the free surface was markedly faster than that through the bulk, and that the crystal growth rate decreased observably after spraying an ultrathin melting gold (10 nm) at the free surface of the drug.  These results indicated that the high growth rates of amorphous drugs crystals at the free surface were the key to their stability and that an ultrathin coating could be applied to enhance the stability of amorphous drugs.