Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana, USA.
Pharm Res. 2012 Oct;29(10):2738-53. doi: 10.1007/s11095-012-0759-8. Epub 2012 May 12.
To examine the precipitation and supersaturation behavior of ten weak bases in terms of the relationship between pH-concentration-time profiles and the solid state properties of the precipitated material.
Initially the compound was dissolved at low pH, followed by titration with base to induce precipitation. Upon precipitation, small aliquots of acid or base were added to induce slight subsaturation and supersaturation respectively and the resultant pH gradient was determined. The concentration of the unionized species was calculated as a function of time and pH using mass and charge balance equations.
Two patterns of behavior were observed in terms of the extent and duration of supersaturation arising following an increase in pH and this behavior could be rationalized based on the crystallization tendency of the compound. For compounds that did not readily crystallize, an amorphous precipitate was formed and a prolonged duration of supersaturation was observed. For compounds that precipitated to crystalline forms, the observed supersaturation was short-lived.
This study showed that supersaturation behavior has significant correlation with the solid-state properties of the precipitate and that pH-metric titration methods can be utilized to evaluate the supersaturation behavior.
通过考察 pH-浓度-时间曲线与沉淀物质的固态特性之间的关系，研究十种弱碱的沉淀和过饱和度行为。
首先将化合物在低 pH 下溶解，然后用碱滴定诱导沉淀。沉淀后，加入少量的酸或碱以分别诱导轻微的亚饱和和过饱和，并确定所得的 pH 梯度。通过质量和电荷平衡方程，计算未离解物种随时间和 pH 的浓度。
观察到在 pH 增加后，过饱和度的程度和持续时间呈现出两种行为模式，这种行为可以根据化合物的结晶倾向进行合理化解释。对于不易结晶的化合物，形成无定形沉淀，观察到过饱和度持续时间较长。对于沉淀为结晶形式的化合物，观察到的过饱和度是短暂的。
本研究表明，过饱和度行为与沉淀的固态特性有显著的相关性，并且 pH 滴定法可用于评估过饱和度行为。
