Formation mechanism of amorphous drug nanoparticles using the antisolvent precipitation method elucidated by varying the preparation temperature
Formation mechanism of amorphous drug nanoparticles using the antisolvent precipitation method elucidated by varying the preparation temperature
复制标题
通过改变制备温度阐明反溶剂沉淀法非晶态药物纳米颗粒的形成机制
DOI：
10.1016/j.ijpharm.2021.121210
复制
发表时间：
2021
影响因子：
5.8
通讯作者：
Moribe Kunikazu
中科院分区：
文献类型：
--
作者：
Morikawa Chikako;Ueda Keisuke;Omori Masaki;Higashi Kenjirou;Moribe Kunikazu
本研究重点研究了制备温度对非晶态药物纳米粒物化性质的影响，以阐明其形成机理。采用两种抗溶剂沉淀法在4~40℃的温度下制备了无定形格列本脲纳米粒。在方法A中，将N，N-二甲基甲酰胺(DMF)溶液加入含有羟丙基甲基纤维素(HPMC)的水溶液中，得到纳米A悬浮液。在方法B中，通过在水中加入同时含有GLB和HPMC的DMF溶液来获得纳米B悬浮液。当制备温度高于25℃时，纳米A和纳米B具有相似的HPMC组成。然而，在低于20℃的温度下，与纳米A相比，纳米B含有大量的HPMC。纳米颗粒核心的玻璃性限制了HPMC从非晶态GLB纳米颗粒向水相的扩散，这表明由于非晶态GLB的纳米尺寸和吸水作用，整洁的非晶态GLB73°C的玻璃化转变温度(Tg)将显著降低。随着纳米颗粒中HPMC含量的增加，非晶态GLB纳米颗粒的物理稳定性提高。因此，通过考虑抗溶剂饱和的无定形药物纳米粒的玻璃化温度来确定制备温度是制备稳定的无定形药物纳米粒的关键。
The present study focuses on the effect of the preparation temperature on the physicochemical properties of amorphous drug nanoparticles to clarify their formation mechanism. Amorphous glibenclamide (GLB) nanoparticles were prepared at 4–40 °C using two antisolvent precipitation methods. In method A,N,N-dimethylformamide (DMF) solution of GLB was added to an aqueous solution containing hydroxypropyl methylcellulose (HPMC) to obtain nano-A suspensions. In method B, nano-B suspensions were obtained by adding DMF solution containing both GLB and HPMC into water. When the preparation temperature was above 25 °C, nano-A and nano-B showed similar HPMC compositions. However, nano-B contained a large amount of HPMC compared to nano-A at temperatures below 20 °C. The glassy nature of the nanoparticle cores restricts the diffusion of HPMC from amorphous GLB nanoparticles to the aqueous phase, indicating that the glass transition temperature (Tg) of neat amorphous GLB (73 °C) would be considerably decreased owing to the nanosizing and water sorption of amorphous GLB. The physical stability of amorphous GLB nanoparticles was improved with increased HPMC in the nanoparticles. Thus, setting the preparation temperature by considering theTgof the antisolvent-saturated amorphous drug nanoparticles is essential to develop stable amorphous drug nanoparticles.