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Polymer-Assisted Aripiprazole–Adipic Acid Cocrystals Produced by Hot Melt Extrusion Techniques
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2020-06-02 , DOI: 10.1021/acs.cgd.0c00020
Arun Butreddy 1 , Sandeep Sarabu 1 , Suresh Bandari 1 , Nagireddy Dumpa 1 , Feng Zhang 2 , Michael A Repka 1, 3
Affiliation  

Pharmaceutical cocrystals offer 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 polymeric matrix (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 (SEM), and hot-stage microscopy. FTIR spectra revealed non-covalent 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 their suitability in the development of solid dosage forms.

中文翻译:

通过热熔挤出技术生产的聚合物辅助的阿立哌唑-己二酸共晶体

药物共晶体提供了增加难溶性药物的溶解度和溶解速度的有前途的策略。但是,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)方法生产共晶体,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辅酶。研究了普通ARP-ADP物理混合物(PM)与含5%Soluplus聚合物基质(SOL)的PM的可加工性。将5%SOL掺入ARP-ADP共混物中可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,通过差示扫描量热法(DSC),傅立叶变换红外(FTIR)光谱,核磁共振(NMR)光谱,粉末X射线衍射(PXRD),扫描电子显微镜(SEM)和热台显微镜对共晶体进行表征。FTIR光谱揭示了ARP和ADP之间的非共价相互作用,这已通过NMR光谱证实。同样,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,共晶具有更高的溶出速率和更高的可压缩性,以及增强的流动特性,表明它们适用于固体剂型的开发。扫描电子显微镜(SEM)和热台显微镜。FTIR光谱揭示了ARP和ADP之间的非共价相互作用,这已通过NMR光谱证实。同样,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,共晶具有更高的溶出速率和更高的可压缩性,以及增强的流动特性,表明它们适用于固体剂型的开发。扫描电子显微镜(SEM)和热台显微镜。FTIR光谱揭示了ARP和ADP之间的非共价相互作用,这已通过NMR光谱证实。同样,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,共晶具有更高的溶出速率和更高的可压缩性,以及增强的流动特性,表明它们适用于固体剂型的开发。
更新日期:2020-07-01
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