Polymer-Assisted Aripiprazole–Adipic Acid Cocrystals Produced by Hot Melt Extrusion Techniques

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.

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Arun Butreddy, Sandeep Sarabu, Suresh Bandari, Nagireddy Dumpa, Feng Zhang, and Michael A. Repka
Cryst. Growth Des. 2020,
https://doi.org/10.1021/acs.cgd.0c00020

SUBJECTS: Fourier transform infrared spectroscopy, Dissolution, Differential scanning calorimetry,