Enhancing the Pharmaceutical Behavior of Nateglinide by Cocrystallization: Physicochemical Assessment of Cocrystal Formation and Informed Use of Differential Scanning Calorimetry for Its Quantitative Characterization

• Published in: Journal of pharmaceutical sciences Vol. 108; no. 4; p. 1529
• Main Authors: Bruni, Giovanna, Maggi, Lauretta, Mustarelli, Piercarlo, Sakaj, Mirena, Friuli, Valeria, Ferrara, Chiara, Berbenni, Vittorio, Girella, Alessandro, Milanese, Chiara, Marini, Amedeo
• Format: Journal Article
• Language: English
• Published: United States 01-04-2019
• Subjects: Administration, Oral; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical - methods; Drug Liberation; Hydrogen-Ion Concentration; Hypoglycemic Agents - analysis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacokinetics; Nateglinide - analysis; Nateglinide - chemistry; Nateglinide - pharmacokinetics; Powder Diffraction; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; calorimetry (DSC); dissolution rate; solid-state NMR; FTIR; X-ray diffractometry; nateglinide; solvent evaporation; solubility; cocrystals
• ISSN: 1520-6017
• DOI: 10.1016/j.xphs.2018.11.033

The aim of this study was to synthetize cocrystals of nateglinide, an antidiabetic agent of biopharmaceutics classification system Class IIa, as a strategy to improve both the solubility and the dissolution rate of the drug. Benzamide was selected by a screening procedure as a suitable coformer, and binary mixtures with different compositions were prepared and analyzed by differential scanning calorimetry (DSC). An in-depth analysis of DSC data allowed obtaining both the eutectic mixture and cocrystal compositions. The rationale of such an analysis was highlighted and explained. Cocrystals were prepared by kneading and solvent evaporation. Their formation was proved by DSC and confirmed by X-ray powder diffraction, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. The functional groups involved in the interaction leading to cocrystals formation were investigated by spectroscopic techniques. The in vitro dissolution profiles show that cocrystals have definite better pharmaceutical performances than the pure drug.