Solubility Measurement and Correlation of Probenecid in 12 Pure Organic Solvents and Thermodynamic Properties of Mixing of Solutions

Abstract

The solubility data of probenecid in 12 different organic solvents including methanol, methyl acetate, ethanol, ethyl acetate, n-propanol, n-butanol, butyl acetate, n-pentanol, isopropanol, isobutanol, acetone, and methyl tert-butyl ether was measured using the gravimetric method over the temperatures range from 283.15 to 323.15 K at 0.1 MPa. The acetone had much higher solubility to probenecid than to other solvents. Three models, including the modified Apelblat equation, the van’t Hoff model, and the nonrandom two-liquid (NRTL) model, were applied to correlate the measured solubility data. The correlation results were evaluated by the average relative deviation (ARD). All of the ARD values were less than 4.522%, which indicated that the three models have a satisfactory correlation. The thermodynamic properties of mixing of probenecid in 12 pure organic solvents including the enthalpy of mixing, Gibbs energy of mixing, and entropy of mixing were calculated by the NRTL model using the correlation results.

Particle Size and Crystal Habit Modification of Active Pharmaceutical Ingredient Using Cooling Sonocrystallization: A Case Study of Probenecid

“…To further screen the solvent from the viewpoint of theoretical recovery, the temperature dependences of solubility of probenecid in acetone, ethanol, ethyl acetate and methanol were acquired from the literature. [ 36 ] The solubilities of probenecid in the remaining two solvents, acetonitrile and dichloromethane, were determined experimentally in this study.…”

“…According to the solubility difference at high and low temperature, theoretical recovery of cooling crystallization can be evaluated. From the van't Hoff parameters acquired from the study of Shi et al., [ 36 ] and regressed from the solubility measurement in this study, solubility values of probenecid in acetone, acetonitrile, ethanol, ethyl acetate and methanol at 323.2 and 273.2 K, and solubility values of probenecid in dichloromethane at 303.2 and 273.2 K were calculated and listed in Table 4 . According to the solubility values, theoretical recovery was then calculated, and four solvents namely acetonitrile, ethanol, ethyl acetate and methanol were finally selected in sonocrystallization experiments since their theoretical recoveries were higher than 80%.…”

“…According to the study of Shi et al., solubility data of probenecid in various organic solvents were reported. [ 36 ] To extend the solubility database of probenecid, this study measured the solubilities of probenecid in acetonitrile and dichloromethane at 288.2–328.2 and 288.2–308.2 using a gravimetric method. Owing to the limitation of normal boiling temperature, the solubilities of probenecid in dichloromethane were measured up to 308.3 K. For solubility measurement using the gravimetric method, an excess amount of probenecid was added in acetonitrile or dichloromethane in a 50 mL glass vial.…”

Solubility Measurement and Data Correlation of Pentaerythritol in Four Binary Solvent Systems at Temperatures from 283.15 to 323.15 K

“…The solubility of APIs is the basis of solvent selection and design for the crystallization process, which plays an important role in the purity, crystal habit, and particle size of the product. − Moreover, solubility is the key factor that affects the pharmacological bioavailability and the therapeutic effects in the human body . According to the previous studies, the solubility of PE in water has been studied by some researchers. ,,, Yet, to the best of our knowledge, no solubility data of PE in binary solvents have been reported in the literature.…”

“…10−13 Moreover, solubility is the key factor that affects the pharmacological bioavailability and the therapeutic effects in the human body. 14 According to the previous studies, the solubility of PE in water has been studied by some researchers. 3,5,6,15 Yet, to the best of our knowledge, no solubility data of PE in binary solvents have been reported in the literature.…”