Physicochemical and mechanical properties of paracetamol cocrystal with 5-nitroisophthalic acid

• Published in: International journal of pharmaceutics Vol. 497; no. 1-2; pp. 106 - 113
• Main Authors: Hiendrawan, Stevanus, Veriansyah, Bambang, Widjojokusumo, Edward, Soewandhi, Sundani Nurono, Wikarsa, Saleh, Tjandrawinata, Raymond R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.01.2016
• Subjects: 5-Nitroisophhthalic acid; Acetaminophen - chemistry; Chemical Phenomena; Cocrystal; Crystallization; Crystallography, X-Ray; Dissolution rate; Drug Liberation; Drug Stability; Mechanical Phenomena; Mechanical properties; Paracetamol; Phthalic Acids - chemistry; Solubility; Potassium dihydrogen phosphate (PubChem CID: 516951); Sodium hydroxide (PubChem CID: 14798); Paracetamol; 5-Nitroisophthalic acid (PubChem CID: 12069); Dissolution rate; Cocrystal; Mechanical properties; 5-Nitroisophhthalic acid; API; Paracetamol (PubChem CID: 1983); Acetonitrille (PubChem CID: 6342); Methanol (PubChem CID: 887)
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2015.12.001

[Display omitted] We report novel pharmaceutical cocrystal of a popular antipyretic drug paracetamol (PCA) with coformer 5-nitroisophhthalic acid (5NIP) to improve its tabletability. The cocrystal (PCA-5NIP at molar ratio of 1:1) was synthesized by solvent evaporation technique using methanol as solvent. The physicochemical properties of cocrystal were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), fourier transform infrared spectroscopy (FTIR), hot stage polarized microscopy (HSPM) and scanning electron microscopy (SEM). Stability of the cocrystal was assessed by storing them at 40°C/75% RH for one month. Compared to PCA, the cocrystal displayed superior tableting performance. PCA-5NIP cocrystal showed a similar dissolution profile as compared to PCA and exhibited good stability. This study showed the utility of PCA-5NIP cocrystal for improving mechanical properties of PCA.