Friedrich I, Reichl S, Müller-Goymann C C
Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstrasse 1, D-38106 Braunschweig, Germany.
Int J Pharm. 2005 Nov 23;305(1-2):167-75. doi: 10.1016/j.ijpharm.2005.09.007. Epub 2005 Oct 19.
Solidified reverse micellar solutions (SRMS), i.e. mixtures of lecithin and triglycerides, offer high solubilisation capacities for different types of drugs in contrast to simple triglyceride systems [Friedrich, I., Müller-Goymann, C.C., 2003. Characterisation of SRMS and production development of SRMS-based nanosuspensions. Eur. J. Pharm. Biopharm. 56, 111-119]. Nanosuspensions based on SRMS were prepared by homogenisation close to the melting point of the SRMS matrix. In a first step the SRMS matrices of 1:1 (w/w) ratios of lecithin and triglycerides were loaded with 17beta-estradiol-hemihydrate (EST), hydrocortisone (HC) or pilocarpine base (PB), respectively, and subsequently ground in liquid nitrogen to minimise drug diffusion later on. The powder was then dispersed in a polysorbate 80 solution using high pressure homogenisation. The drug loading capacities of the nanosuspensions were very high in the case of poorly water-soluble EST (99% of total 0.1%, w/w, EST) and HC (97% of total 0.5%, w/w, HC) but not sufficient with the more hydrophilic PB (37-40% of total 1.0%, w/w, PB). These findings suggest SRMS-based nanosuspensions to be promising aqueous drug carrier systems for poorly soluble drugs like EST and HC. Furthermore, in vitro drug permeation from the different drug-loaded nanosuspensions was performed across human cornea construct (HCC) as an organotypical cell culture model. PB permeation did not differ from the nanosuspension and an aqueous solution whereas the permeation coefficients of HC-loaded nanosuspensions were reduced in comparison to aqueous and oily solutions of HC. However, the permeated amount was higher from the nanosuspensions due to a much lower HC concentration in the solution than that in the nanosuspension (solution 0.02%, w/w, versus nanosuspension 0.5%, w/w). The high drug load of the nanoparticles provides prolonged HC release. Permeated amounts of EST were reduced in comparison to HC and only detectable with an ELISA technique. The EST release from nanosuspensions and different EST-loaded systems revealed a prolonged EST release from the nanoparticulate systems in contrast to a faster release of an oily solution of an equal EST concentration. With regard to an aqueous EST suspension of similar concentration which represents a depot system the release rate from the nanosuspensions revealed the same order of magnitude which points again to a prolonged release potential of the nanosuspensions.
固化反胶束溶液（SRMS），即卵磷脂和甘油三酯的混合物，与简单的甘油三酯体系相比，对不同类型药物具有高增溶能力[Friedrich, I., Müller-Goymann, C.C., 2003. SRMS的表征及基于SRMS的纳米混悬液的生产开发。欧洲药理学与生物药剂学杂志56, 111 - 119]。基于SRMS的纳米混悬液通过在接近SRMS基质熔点的条件下均质化制备。第一步，分别将1:1（w/w）比例的卵磷脂和甘油三酯的SRMS基质负载半水合17β-雌二醇（EST）、氢化可的松（HC）或毛果芸香碱碱（PB），随后在液氮中研磨以尽量减少后续药物扩散。然后使用高压均质化将粉末分散在聚山梨酯80溶液中。对于水溶性差的EST（占总0.1%，w/w，EST的99%）和HC（占总0.5%，w/w，HC的97%），纳米混悬液的载药量非常高，但对于亲水性更强的PB（占总1.0%，w/w，PB的37 - 40%）则不足。这些发现表明基于SRMS的纳米混悬液对于像EST和HC这样的难溶性药物是有前景的水性药物载体系统。此外，以人角膜构建体（HCC）作为器官型细胞培养模型，对不同载药纳米混悬液进行了体外药物渗透实验。PB的渗透与纳米混悬液和水溶液没有差异，而载HC纳米混悬液的渗透系数与HC的水溶液和油溶液相比有所降低。然而，由于溶液中HC浓度比纳米混悬液中低得多（溶液0.02%，w/w， versus纳米混悬液0.5%，w/w），纳米混悬液的渗透量更高。纳米颗粒的高载药量使HC释放延长。与HC相比，EST的渗透量降低，且仅用ELISA技术可检测到。与相同EST浓度的油溶液更快释放相比，纳米混悬液和不同载EST体系中EST的释放显示纳米颗粒体系中EST释放延长。对于代表长效制剂系统的类似浓度的EST水性混悬液，纳米混悬液的释放速率显示出相同的数量级，这再次表明纳米混悬液具有延长释放的潜力。
