Lee Tu, Zhang Chyong Wen
Department of Chemical and Materials Engineering, National Central University, 300 Jhong-Da Rd, Jhong-Li City 320, Taiwan, Republic of China.
Pharm Res. 2008 Jul;25(7):1563-71. doi: 10.1007/s11095-008-9554-y. Epub 2008 Feb 27.
The aim of this paper is to enhance the dissolution rate of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate via a bio-inspired method of growing mesocrystals.
Mesocrystals of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate were successfully prepared from a supersaturated aqueous solution of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate having the initial degree of supersaturation, S ( 0 ), of 1.326 and the initial saturated concentration, C*, of 0.986 mol/l at 25 degrees C with sodium dodecyl sulfate (SDS) at a concentration of 0.10 g/l. Dynamic light scattering, scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and optical microscopy with cross polarizers were employed to understand the formation mechanism and to characterize the superstructures of the SDS generated mesocrystals.
The SDS generated mesocrystals were the assembly of the oriented attachment of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate nano-sized platelets under the mediation of the side-to-side interaction between SDS and racemic (R,S)-(+/-)-sodium ibuprofen dihydrate. The SDS generated mesocrystals contained a mixture of the racemic compounds in alpha- and beta-forms and the resolved racemic conglomerate in gamma-form with no detectable amount of SDS. The dissolution rate of the SDS generated mesocrystals was more rapid than the one of its counterpart made by conventional crystallization pathway.
The crystallization of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate in the presence of SDS yielded well-faceted, well-separated, but almost perfectly three-dimensionally aligned nano-sized platelets. This kind of bio-inspired mesocrystal superstructure has definitely opened a new doorway for crystal engineering and pre-formulation design in pharmaceutical industry. The future work is to study the mesocrystal formation of some other active pharmaceutical ingredients in organic solvent systems and to develop an efficient method for screening the additives.
本文旨在通过一种受生物启发的生长介晶方法提高外消旋（R，S）-（±）-布洛芬二水合钠的溶解速率。
以外消旋（R，S）-（±）-布洛芬二水合钠的过饱和水溶液成功制备了外消旋（R，S）-（±）-布洛芬二水合钠介晶，该过饱和水溶液在25℃下的初始过饱和度S(0)为1.326，初始饱和浓度C*为0.986 mol/l，含有浓度为0.10 g/l的十二烷基硫酸钠（SDS）。采用动态光散射、扫描电子显微镜、粉末X射线衍射、差示扫描量热法以及带有交叉偏振器的光学显微镜来了解形成机制并表征SDS生成的介晶的超结构。
SDS生成的介晶是外消旋（R，S）-（±）-布洛芬二水合钠纳米尺寸薄片在SDS与外消旋（R，S）-（±）-布洛芬二水合钠之间的侧向相互作用介导下定向附着的聚集体。SDS生成的介晶包含α-和β-形式的外消旋化合物混合物以及γ-形式的拆分外消旋聚集体，且未检测到SDS。SDS生成的介晶的溶解速率比通过传统结晶途径制备的对应物更快。
在SDS存在下外消旋（R，S）-（±）-布洛芬二水合钠的结晶产生了晶面良好、分离良好但几乎完美三维排列的纳米尺寸薄片。这种受生物启发的介晶超结构无疑为制药行业的晶体工程和预制剂设计打开了一扇新的大门。未来的工作是研究一些其他活性药物成分在有机溶剂体系中的介晶形成，并开发一种筛选添加剂的有效方法。
