Solventless granulation and spheronization of indomethacin crystals using a mechanical powder processor: Effects of mechanically induced amorphization on particle formation
Solventless granulation and spheronization of indomethacin crystals using a mechanical powder processor: Effects of mechanically induced amorphization on particle formation
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使用机械粉末加工机对吲哚美辛晶体进行无溶剂造粒和滚圆：机械诱导的非晶化对颗粒形成的影响
DOI：
10.1016/j.ejpb.2020.07.031
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发表时间：
2020
影响因子：
4.9
通讯作者：
Toshiyuki Niwa
中科院分区：
文献类型：
--
作者：
Keita Kondo;Koki Miyamoto;Sayaka Miura;Toshiyuki Niwa
我们的目的是揭示机械诱导非晶化对药物晶体无溶剂团聚和滚圆化的影响。该工艺可提供100%含药物的球形颗粒。采用不同夹套温度对吲哚美辛晶体进行机械处理，并用颗粒和晶体分析对所得颗粒进行表征。并对非晶态吲哚美辛的粘附性能和力学性能进行了测试。在20℃时，吲哚美辛晶体在加工过程中破碎、非晶化，说明无粘附性的玻璃态吲哚美辛不会形成团聚或球化。在40℃时，由于机械诱导的非晶态相在玻璃化转变温度附近从非粘接玻璃转变为粘接过冷液体而发生团聚。然而，在较高温度下，非晶表面的再结晶抑制了团聚体的形成。在60℃时，由于颗粒表面的变形，吲哚美辛晶体致密、球化，这与60℃以上非晶态吲哚美辛刚度突然下降的结果一致。非晶相的寿命随着温度的升高而降低，这是由于再结晶的增强，从而降低了球化的程度。综上所述，机械诱导非晶相的玻璃化转变温度和再结晶影响团聚和球化。
Our aim was to reveal the effects of mechanically-induced amorphization on the solventless agglomeration and spheronization of drug crystals using a mechanical powder processor. This process can provide spherical particles comprising 100% drug. Indomethacin crystals were mechanically treated using various jacket temperatures and the resulting particles were characterized using particle and crystalline analyses. Also, the adhesive and mechanical properties of amorphous indomethacin were examined. At 20 °C, the indomethacin crystals fragmented and amorphized during processing, indicating that glassy-state indomethacin with no adhesiveness does not contribute to agglomeration or spheronization. At 40 °C, agglomeration occurred due to the transformation of mechanically-induced amorphous phases from non-adhesive glass to an adhesive supercooled liquid at around the glass transition temperature. However, at higher temperatures, the formation of agglomerates was suppressed by recrystallization of the amorphous surface. At 60 °C, the indomethacin crystals compacted and spheronized due to deformation of the particle surface, consistent with results showing that the stiffness of amorphous indomethacin decreased suddenly above 60 °C. The lifespan of the amorphous phase decreased due to enhanced recrystallization as the temperature increased, thereby reducing the degree of spheronization. In conclusion, agglomeration and spheronization are affected by the glass transition temperature and recrystallization of the mechanically-induced amorphous phase.