Co-Crystal of Paracetamol and Trimethylglycine Prepared by a Supercritical CO2 Anti-Solvent Process

Paracetamol (PCA) and trimethylglycine (TMG) were co-crystallized and micronized by means of the supercritical anti-solvent (SAS) process to improve the tabletability of PCA. The effects of operating conditions on particle properties were investigated in detail. Characterizations were performed to confirm the co-crystal state of PCA-TMG. The results indicated that the same crystal form with different crystal habits was prepared. The optimal PCA-TMG co-crystals presented a much larger tensile strength, higher drug content of PCA, and smaller particle size than those obtained using the ball milling (BM) process. The SAS-processed PCA-TMG co-crystals showed an enhanced solubility, dissolution rate, and tableting performance compared to that of BM.