A Method to Evaluate the Effect of Contact with Excipients on the Surface Crystallization of Amorphous Drugs

作者：Zhang Si Wei; Yu Lian; Huang Jun; Hussain Munir A; Derdour Lotfi; Qian Feng; de Villiers Melgardt M^*

来源：AAPS PHARMSCITECH, 2014, 15(6): 1516-1526.

DOI：10.1208/s12249-014-0178-8

• amorphous
• drugs
• growth rate
• nucleation rate
• tablet excipients

Amorphous drugs are used to improve the solubility, dissolution, and bioavailability of drugs. However, these metastable forms of drugs can transform into more stable, less soluble, crystalline counterparts. This study reports a method for evaluating the effect of commonly used excipients on the surface crystallization of amorphous drugs and its application to two model amorphous compounds, nifedipine and indomethacin. In this method, amorphous samples of the drugs were covered by excipients and stored in controlled environments. An inverted light microscope was used to measure in real time the rates of surface crystal nucleation and growth. For nifedipine, vacuum-dried microcrystalline cellulose and lactose monohydrate increased the nucleation rate of the beta polymorph from two to five times when samples were stored in a desiccator, while D-mannitol and magnesium stearate increased the nucleation rate 50 times. At 50% relative humidity, the nucleation rates were further increased, suggesting that moisture played an important role in the crystallization caused by the excipients. The effect of excipients on the crystal growth rate was not significant, suggesting that contact with excipients influences the physical stability of amorphous nifedipine mainly through the effect on crystal nucleation. This effect seems to be drug specific because for two polymorphs of indomethacin, no significant change in the nucleation rate was observed under the excipients.

• 出版日期2014-12
• 单位清华大学