Friedrich I, Müller-Goymann C C
Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany.
Eur J Pharm Biopharm. 2003 Jul;56(1):111-9. doi: 10.1016/s0939-6411(03)00043-2.
Solidified reverse micellar solutions (SRMS), i.e. binary mixtures of 30-60% (w/w) lecithin and two different hard fats, were investigated regarding their physicochemical properties and the influence of lecithin on solid lipids. For this purpose, the systems were characterized with X-ray and thermal analysis, transmission electron microscopy (TEM) and photon correlation spectroscopy. The melting point (m.p.) of the solid lipids, which is a crucial parameter of the solid state, was not altered up to a lecithin concentration of 50% whereas reverse micelles were likely to be frozen still in the solid state. In addition, solubilities of 17beta-oestradiol-hemihydrate, pilocarpine base and hydrochloride in the SRMS melt were studied for evaluation of the drug carrier potency. Drug solubilization in the SRMS melt increased linearly with rising amount of lecithin. SRMS-based nanosuspensions were developed with a given lecithin/hard fat ratio of 1:1 (w/w). High-pressure homogenization was applied on cold to avoid lecithin loss. Optimization of the systems in terms of a variation of the homogenizing parameters such as pressure, number of cycles and temperature resulted in nanoparticulate systems with a polysorbate 80/SRMS ratio of 1:5 (w/w), and a total amount of 5 and 15% (w/w) SRMS, respectively. Production temperatures near the lipid m.p. proved best to be maintained by varying the pressure, yielding small nanoparticles with a narrow particle size distribution. The solid lipid nanoparticles were characterized with X-ray and thermal analysis as well as TEM. The crystalline particles (beta modification) are of anisometrical shape and have transition temperatures far below the bulk m.p. due to the colloidal character of the systems.
研究了固化反胶束溶液（SRMS），即30 - 60%（w/w）卵磷脂与两种不同硬脂的二元混合物的物理化学性质以及卵磷脂对固体脂质的影响。为此，采用X射线和热分析、透射电子显微镜（TEM）和光子相关光谱对该体系进行了表征。固体脂质的熔点（m.p.）是固态的关键参数，在卵磷脂浓度达到50%之前未发生改变，而反胶束可能仍以固态冻结。此外，研究了17β - 雌二醇半水合物、毛果芸香碱碱和盐酸盐在SRMS熔体中的溶解度，以评估药物载体效能。药物在SRMS熔体中的增溶量随卵磷脂含量的增加呈线性增加。以给定的1:1（w/w）卵磷脂/硬脂比例开发了基于SRMS的纳米混悬液。对冷态样品进行高压均质以避免卵磷脂损失。通过改变均质参数如压力、循环次数和温度对体系进行优化，得到了聚山梨酯80/SRMS比例为1:5（w/w）、SRMS总量分别为5%和15%（w/w）的纳米颗粒体系。通过改变压力证明最好保持接近脂质熔点的生产温度，从而得到粒径分布窄的小纳米颗粒。用X射线、热分析以及TEM对固体脂质纳米颗粒进行了表征。由于体系的胶体性质，结晶颗粒（β晶型）呈不等轴形状，其转变温度远低于整体熔点。
