Polymer-Assisted Aripiprazole-Adipic Acid Cocrystals Produced by Hot Melt Extrusion Techniques.
Polymer-Assisted Aripiprazole-Adipic Acid Cocrystals Produced by Hot Melt Extrusion Techniques.
复制标题
DOI：
10.1021/acs.cgd.0c00020
复制
发表时间：
2020-07
影响因子：
3.8
通讯作者：
Repka MA
中科院分区：
文献类型：
--
作者：
Butreddy A;Sarabu S;Bandari S;Dumpa N;Zhang F;Repka MA
药物共晶是提高难溶性药物的溶解度和溶出速率的有前途的策略。然而，它们的制造过程需要大量的溶剂。本研究旨在通过无溶剂热熔挤出（HME）方法生产共晶，以提高其溶解度和溶解速率。阿立哌唑（ARP）和己二酸（ADP）分别用作弱碱性药物和酸性共形成物。研究了普通 ARP-ADP 物理混合物 (PM) 与含 5% Soluplus® (SOL) 的 PM 的加工性能。在 ARP-ADP 混合物中加入 5% SOL 可以降低加工扭矩并提高加工性能。研究了温度和螺杆转速对共晶形成的影响，并通过差示扫描量热法（DSC）、傅里叶变换红外光谱（FTIR）、核磁共振（NMR）光谱、粉末X射线衍射（PXRD）、扫描电子显微镜和热台显微镜对共晶进行了表征。 FTIR 光谱揭示了 ARP 和 ADP 之间的非共价相互作用，这一点得到了 NMR 光谱的证实。类似地，PXRD 数据显示出特征峰，证实了新晶体材料的形成。此外，结果表明，与纯 ARP 相比，共晶表现出更高的溶出率和改善的可压缩性，以及增强的流动特性，表明其适合开发固体剂型。通过热熔挤出技术聚合物辅助 ARP-ADP 共晶的示意图。
Pharmaceutical cocrystals are a promising strategy to increase the solubility and dissolution rate of poorly soluble drugs. However, their manufacturing process requires a large quantity of solvents. The present study aimed to produce cocrystals by a solvent-free hot melt extrusion (HME) method to improve their solubility and dissolution rate. Aripiprazole (ARP) and adipic acid (ADP) were used as a weakly basic drug and acidic coformer, respectively. The processability of a plain ARP-ADP physical mixture (PM) compared with a PM with 5% Soluplus® (SOL) was investigated. Incorporating 5% SOL into the ARP-ADP blend reduced the processing torque and improved processability. The effects of temperature and screw speed on the formation of cocrystals were studied, and cocrystals were characterized by differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy, and hot-stage microscopy. FTIR spectra revealed noncovalent interaction between ARP and ADP, which was confirmed by NMR spectra. Similarly, PXRD data exhibited characteristic peaks confirming the formation of new crystalline material. Further, the results indicated that cocrystals demonstrated higher dissolution rates and improved compressibility, as well as enhanced flow characteristics compared with pure ARP, suggesting its suitability in the development of solid dosage forms. Schematic representation of polymer assisted ARP-ADP cocrystals via hot melt extrusion technique.
登录
查看更多内容
影响因子：
4.9
作者：
Liu, Xu;Zhou, Lin;Zhang, Feng
通讯作者：
Zhang, Feng
影响因子：
5.8
作者：
Karimi-Jafari, Maryam;Ziaee, Ahmad;Walker, Gavin
通讯作者：
Walker, Gavin
影响因子：
4.6
作者：
Aher, Suyog;Dhumal, Ravindra;York, Peter
通讯作者：
York, Peter
影响因子：
3.4
作者：
Daurio, Dominick;Nagapudi, Karthik;Nunez, Fernando-Alvarez
通讯作者：
Nunez, Fernando-Alvarez
DOI：
10.1107/s2053229618017904
发表时间：
2019-02-01
影响因子：
0.8
作者：
Borodi, Gheorghe;Turza, Alexandru;Bende, Attila
通讯作者：
Bende, Attila