Fehér A, Urbán E, Eros I, Szabó-Révész P, Csányi E
Department of Pharmaceutical Technology, University of Szeged, Eötvös Street 6, Szeged, Hungary.
Int J Pharm. 2008 Jun 24;358(1-2):23-6. doi: 10.1016/j.ijpharm.2008.02.025. Epub 2008 Feb 29.
The aim of our study was to develop water-free lyotropic liquid crystalline preconcentrates, which consist of oils and surfactants with good physiological tolerance and spontaneously form lyotropic liquid crystalline phase in aqueous environment. In this way these preconcentrates having low viscosity can be injected into the periodontal pocket, where they are transformed into highly viscous liquid crystalline phase, so that the preparation is prevented from flowing out of the pocket due to its great viscosity, while drug release is controlled by the liquid crystalline texture. In order to follow the structure alteration upon water absorption polarization microscopical and rheological examinations were performed. The water absorption mechanism of the samples was examined by the Enslin-method. Metronidazole-benzoate was used as active agent the release of which was characterized via in vitro investigations performed by means of modified Kirby-Bauer disk diffusion method. On the grounds of the results it can be stated that the 4:1 mixture of the investigated surfactants (Cremophor EL, Cremophor RH40) and oil (Miglyol 810) formed lyotopic liquid crystalline phases upon water addition. Polarization microscopic examinations showed that samples with 10-40% water content possessed anisotropic properties. On the basis of water absorption, rheological and drug release studies it can be concluded that the amount of absorbed water and stiffness of lyotropic structure influenced by the chemical entity of the surfactant exerted major effect on the drug release.
我们研究的目的是开发无水溶致液晶预浓缩物,其由具有良好生理耐受性的油和表面活性剂组成,并在水性环境中自发形成溶致液晶相。通过这种方式,这些低粘度的预浓缩物可以注入牙周袋,在那里它们转变为高粘度的液晶相,从而由于其高粘度防止制剂从袋中流出,同时药物释放由液晶结构控制。为了跟踪吸水后的结构变化,进行了偏振显微镜和流变学检查。通过恩斯林法研究了样品的吸水机制。甲硝唑苯甲酸酯用作活性剂,其释放通过采用改良的 Kirby-Bauer 纸片扩散法进行的体外研究来表征。根据结果可以表明,所研究的表面活性剂(聚氧乙烯蓖麻油 EL、聚氧乙烯蓖麻油 RH40)和油(Miglyol 810)的 4:1 混合物加水后形成了溶致液晶相。偏振显微镜检查表明,含水量为 10-40% 的样品具有各向异性特性。基于吸水、流变学和药物释放研究可以得出结论,表面活性剂的化学性质影响的吸水量和溶致结构的硬度对药物释放有主要影响。