Department of Chemical and Environmental Science, Synthesis and Solid State Pharmaceutical Centre (SSPC), Bernal Institute, University of Limerick, Castletroy, Ireland; Department of Chemical Engineering, KTH Royal Institute of Technology, Teknikringen 42, SE-10044 Stockholm, Sweden.
Department of Chemical Engineering, KTH Royal Institute of Technology, Teknikringen 42, SE-10044 Stockholm, Sweden.
J Pharm Sci. 2019 Jul;108(7):2377-2382. doi: 10.1016/j.xphs.2019.02.013. Epub 2019 Feb 23.
The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-propanol, 1-butanol, and toluene over the temperature range 268-298 K. Polymorph transition and melting temperatures, associated enthalpy changes, and the heat capacity of the solid forms and the supercooled melt have been measured by differential scanning calorimetry. Based on extrapolated calorimetric data, the Gibbs energy, enthalpy and entropy of fusion, and the activity of solid butamben (the ideal solubility) have been calculated from below ambient temperature up to the melting point. Activity coefficients of butamben at equilibrium in the different solvents have been estimated from solubility data and the activity of the solid, revealing that all investigated systems exhibit positive deviation from Raoult's law. Solubility data are well correlated by a semiempirical regression model. On a mass basis, the solubility is clearly higher in methanol than in the other solvents, but mole fraction solubilities are very similar across all 5 solvents. The 2 known polymorphs are enantiotropically related, and the transition point is located at 283 K. Polymorph interconversions occur within 0.3 K of the transition point even in the solid state, and the 2 forms exhibit strong similarities in investigated properties.
已通过重量法在 268-298 K 的温度范围内测量了特布他林在纯甲醇、1-丙醇、2-丙醇、1-丁醇和甲苯中的溶解度。通过差示扫描量热法测量了多晶型转变和熔点、相关焓变以及固相和过冷熔体的热容。基于外推的量热数据,从环境温度以下到熔点,计算了熔融的吉布斯自由能、焓和熵,以及固相特布他林的活度(理想溶解度)。从溶解度数据和固相活度估算了不同溶剂中平衡时特布他林的活度系数,表明所有研究的体系均表现出对拉乌尔定律的正偏差。溶解度数据通过半经验回归模型得到了很好的关联。按质量计,特布他林在甲醇中的溶解度明显高于其他溶剂,但在所有 5 种溶剂中,摩尔分数溶解度非常相似。2 种已知的多晶型物是反型相关的,转变点位于 283 K。即使在固态下,多晶型物的转化也发生在转变点的 0.3 K 内,并且这 2 种形式在研究的性质上表现出很强的相似性。