Multicomponent crystalline solid forms of aripiprazole produced via hot melt extrusion techniques: An exploratory study
Multicomponent crystalline solid forms of aripiprazole produced via hot melt extrusion techniques: An exploratory study
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DOI：
10.1016/j.jddst.2021.102529
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发表时间：
2021-04-24
影响因子：
5
通讯作者：
Repka, Michael A.
中科院分区：
文献类型：
--
作者：
Butreddy, Arun;Almutairi, Mashan;Repka, Michael A.
多组分结晶固体形式（盐、共晶和共晶）是增强难溶性药物的溶出行为的有前景的手段。本研究表明，多组分固体形式的阿立哌唑（阿普）的制备与琥珀酸（SA）和烟酰胺（NA）作为共成型剂，使用热熔挤出（HME）技术的发展。采用差示扫描量热法（DSC）、热台显微镜（HSM）、傅里叶变换红外光谱（FTIR）、粉末X射线衍射（PXRD）和扫描电子显微镜（SEM）对热机械处理后的样品进行了表征和分析。DSC和HSM分析揭示了固体形式的特征性单一熔融温度，其不同于单个组分的熔点。ARP-SA的FTIR（酰胺C-O伸缩）和PXRD结果中的可辨别的变化证实了新的结晶固体形式的形成。在ARP-NA的情况下，这些变化不太突出，没有峰的出现或消失，表明晶格没有变化。SEM图像显示了HME处理样品与单个母代组件之间的形态差异。体外溶出度和微环境pH值测量研究表明，ARP-SA显示出更高的溶出速率，这可能是由于共形成物赋予的酸性微环境pH值。本研究的观察结果证明了HME技术用于开发阿普多组分固体形式的适用性。
Multicomponent crystalline solid forms (salts, cocrystals and eutectics) are a promising means of enhancing the dissolution behavior of poorly soluble drugs. The present study demonstrates the development of multicomponent solid forms of aripiprazole (ARP) prepared with succinic acid (SA) and nicotinamide (NA) as coformers using the hot melt extrusion (HME) technique. The HME-processed samples were characterized and analyzed using differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and HSM analyses revealed a characteristic single melting temperature in the solid forms, which differed from the melting points of the individual components. The discernible changes in the FTIR (amide C--O stretching) and PXRD results for ARP-SA confirm the formation of new crystalline solid forms. In the case of ARP-NA, these changes were less prominent, without the appearance or disappearance of peaks, suggesting no change in the crystal lattice. The SEM images demonstrated morphological differences between the HME-processed samples and the individual parent components. The in vitro dissolution and microenvironment pH measurement studies revealed that ARP-SA showed a higher dissolution rate, which could be due to the acidic microenvironment pH imparted by the coformer. The observations of the present study demonstrate the applicability of the HME technique for the development of ARP multicomponent solid forms.