Faculty of Science and Technology, Institute of Physics, University of Silesia in Katowice, SMCEBI, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland.
Mol Pharm. 2024 May 6;21(5):2315-2326. doi: 10.1021/acs.molpharmaceut.3c01095. Epub 2024 Apr 21.
The main purpose of our studies is to demonstrate that commercially available mesoporous silica (MS) can be used to control the physical state of aripiprazole (ARP). The investigations performed utilizing differential scanning calorimetry and broadband dielectric spectroscopy reveal that silica can play different roles depending on its concentration in the system with amorphous ARP. At low MS content, it activates recrystallization of the active pharmaceutical ingredient and supports forming the III polymorphic form of ARP. At intermediate MS content (between ca. 27 and 65 wt %), MS works as a recrystallization inhibitor of ARP. At these concentrations, the formation of III polymorphic form is no longer favorable; therefore, it is possible to use this additive to obtain ARP in either IV or X polymorphic form. At the same time, employing MS in concentrations >65 wt % amorphous form of ARP with high physical stability can be obtained. Finally, regardless of the polymorphic form it crystallizes into, each composite is characterized by the same temperature dependence of relaxation times in the supercooled and glassy states.
我们研究的主要目的是证明市售介孔硅（MS）可用于控制阿立哌唑（ARP）的物理状态。利用差示扫描量热法和宽带介电谱进行的研究表明，硅在含有无定形 ARP 的系统中，根据其浓度可以发挥不同的作用。在低 MS 含量下，它可以激活活性药物成分的再结晶，并支持 ARP 的 III 多晶型形式的形成。在中间的 MS 含量（约 27 至 65wt%）下，MS 是 ARP 的再结晶抑制剂。在这些浓度下，不再有利于形成 III 多晶型形式，因此，可以使用这种添加剂来获得 ARP 的 IV 或 X 多晶型形式。同时，在浓度>65wt%的情况下，可获得具有高物理稳定性的 ARP 无定形形式。最后，无论其结晶成哪种多晶型形式，每个复合材料在过冷和玻璃态的弛豫时间温度依赖性上都具有相同的特征。
