Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, 06269, USA.
AAPS PharmSciTech. 2011 Sep;12(3):909-16. doi: 10.1208/s12249-011-9656-4. Epub 2011 Jul 6.
Forming a salt is a common way to increase the solubility of a poorly soluble compound. However, the solubility enhancement gained by salt formation may be lost due to solution-mediated phase transformation (SMPT) during dissolution. The SMPT of a salt can occur due to a supersaturated solution near the dissolving surface caused by pH or other solution conditions. In addition to changes in pH, surfactants are also known to affect SMPT. In this study, SMPT of a highly soluble salt, haloperidol mesylate, at pH 7 in the presence of a commonly used surfactant, sodium lauryl sulfate (SLS), was investigated. Dissolution experiments were performed using a flow-through dissolution apparatus with solutions containing various concentrations of SLS. Compacts of haloperidol mesylate were observed during dissolution in the flow-through apparatus using a stereomicroscope. Raman microscopy was used to characterize solids. The dissolution of haloperidol mesylate was significantly influenced by the addition of sodium lauryl sulfate. In conditions where SMPT was expected, the addition of SLS at low concentrations (0.1-0.2 mM) reduced the dissolution of haloperidol mesylate. In solutions containing concentrations of SLS above the critical micelle concentration (CMC) (10-15 mM), the dissolution of haloperidol mesylate increased compared to below the CMC. The solids recovered from solubility experiments of haloperidol mesylate indicated that haloperidol free base precipitated at all concentrations of SLS. Above 5 mM of SLS, Raman microscopy suggested a new form, perhaps the estolate salt. The addition of surfactant in solids that undergo solution-mediated phase transformation can add complexity to the dissolution profiles and conversion.
形成盐是提高难溶性化合物溶解度的常用方法。然而，盐形成带来的溶解度提高可能会由于溶解过程中的溶液介导的相转变（SMPT）而丧失。盐的 SMPT 可能由于溶解表面附近的过饱和溶液而发生，这是由 pH 或其他溶液条件引起的。除了 pH 的变化外，表面活性剂也已知会影响 SMPT。在这项研究中，研究了在常用表面活性剂十二烷基硫酸钠（SLS）存在下，pH 为 7 时高溶解度盐氟哌啶醇甲磺酸盐的 SMPT。使用包含各种 SLS 浓度的溶液在流通式溶解装置中进行溶解实验。使用立体显微镜在流通式装置中观察到氟哌啶醇甲磺酸盐在溶解过程中的片剂。拉曼显微镜用于对固体进行表征。加入十二烷基硫酸钠显著影响氟哌啶醇甲磺酸盐的溶解。在预期发生 SMPT 的条件下，低浓度（0.1-0.2mM）添加 SLS 会降低氟哌啶醇甲磺酸盐的溶解。在 SLS 浓度高于临界胶束浓度（CMC）（10-15mM）的溶液中，与 CMC 以下相比，氟哌啶醇甲磺酸盐的溶解增加。从氟哌啶醇甲磺酸盐溶解度实验回收的固体表明，在所有 SLS 浓度下都有游离氟哌啶醇碱沉淀。在 SLS 浓度高于 5mM 时，拉曼显微镜表明存在一种新的形式，可能是酯盐。在经历溶液介导的相转变的固体中添加表面活性剂会使溶解曲线和转化复杂化。
