Determination and prediction of solubilities of active pharmaceutical ingredients in selected organic solvents

作者：Matsuda Hiroyuki^*; Mori Kanako; Tomioka Mariko; Kariyasu Nozomi; Fukami Toshiro; Kurihara Kiyofumi; Tochigi Katsumi; Tomono Kazuo

来源：Fluid Phase Equilibria, 2015, 406: 116-123.

DOI：10.1016/j.fluid.2015.07.032

• Solubility
• Pharmaceutical compounds
• Polymorphs
• Activity coefficient model
• Prediction

The aim of this work was to measure the solubilities of active pharmaceutical ingredients (APIs) in various organic solvents using the synthetic-visual method. Two non-steroidal anti-inflammatory drugs, i.e., acetylsalicylic acid and acetaminophen, and two histamine H-2 receptor antagonists, i.e., cimetidine and famotidine, were selected as the APIs. The solubilities of these APIs in different organic solvents, namely methanol, ethanol, 2-propanol, 1-octanol, and poly(ethylene glycol) 400, were determined in the temperature range of 260-360 K. Cimetidine and famotidine, which have several polymorphs, were characterized using powder X-ray diffraction, scanning electron microscopy, and differential scanning calorimetry before the solubility measurements. The experimental results for the APIs except famotidine show that the solubilities at a given temperature decreased with increasing carbon number of the alcohol. The solubility data were represented by two activity coefficient models: NRTL and UNIQUAC. In addition, predictions of the solubilities using the group contribution models Pharma Modified UNIFAC and modified UNIFAC (Dortmund) were also performed.

• 出版日期2015-11-25