Rodríguez-Hornedo N, Murphy D
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan 48109-1065, USA.
J Pharm Sci. 2004 Feb;93(2):449-60. doi: 10.1002/jps.10496.
The influence of two structurally different anionic surfactants on the anhydrous-to-dihydrate transformation of carbamazepine (CBZ) was investigated. The surfactants studied were sodium lauryl sulfate (SLS), a surfactant commonly used in compendial dissolution methods, and sodium taurocholate (STC), an important surfactant in the solubilization and absorption of drugs and lipids in the gastrointestinal tract. Results show that both surfactants promoted the crystallization of CBZ dihydrate [CBZ(D)] during dissolution of the anhydrous monoclinic polymorph [CBZ(A)]). Examination of crystal surfaces showed that SLS facilitated the surface-mediated nucleation of CBZ(D) on CBZ(A) crystals at surfactant concentrations below the critical micelle concentration (cmc). Solubilization of a dye and related color changes provided visual evidence for adsorbed SLS assemblies on CBZ(A) crystal faces below the cmc. Above the cmc, both surfactants promoted the transformation by increasing the bulk nucleation of CBZ(D). STC changed the crystal morphology of CBZ(D) from acicular to prismatic, depending on STC concentration. Such morphology changes originate from interactions between STC and molecular structures of CBZ(D) crystal faces that interfere with the formation of a hydrogen-bonded chain of water molecules and carboxamide dimers.
研究了两种结构不同的阴离子表面活性剂对卡马西平（CBZ）从无水物向二水合物转变的影响。所研究的表面活性剂为月桂醇硫酸酯钠（SLS），一种在药典溶出方法中常用的表面活性剂，以及牛磺胆酸钠（STC），一种在胃肠道药物和脂质增溶及吸收中起重要作用的表面活性剂。结果表明，在无水单斜晶型[CBZ(A)]溶解过程中，两种表面活性剂均促进了CBZ二水合物[CBZ(D)]的结晶。晶体表面检查表明，在表面活性剂浓度低于临界胶束浓度（cmc）时，SLS促进了CBZ(D)在CBZ(A)晶体上的表面介导成核。染料的增溶及相关颜色变化为cmc以下CBZ(A)晶面上吸附的SLS聚集体提供了直观证据。在cmc以上，两种表面活性剂均通过增加CBZ(D)的本体成核来促进转变。STC根据其浓度将CBZ(D)的晶体形态从针状变为棱柱形。这种形态变化源于STC与CBZ(D)晶面分子结构之间的相互作用，这种相互作用干扰了水分子和羧酰胺二聚体氢键链的形成。
