University of Applied Sciences and Arts Northwestern Switzerland, Institute of Pharmaceutical Technology, Gründenstr. 40, CH-4132 Muttenz, Switzerland.
Int J Pharm. 2013 Mar 25;446(1-2):70-80. doi: 10.1016/j.ijpharm.2013.02.005. Epub 2013 Feb 10.
Lipid-based formulations that disperse in water as nano-droplets are of considerable pharmaceutical interest. However, there is a recent debate on which systems form stable swollen micelles rather than other thermodynamically unstable nano-emulsions. This study introduces stability categories for nano-dispersions by considering theoretical arguments of particle size and polydispersity. In a second step, 20 pharmaceutical nano-emulsifying formulations were investigated with respect to the physical stability of the aqueous dispersions. Thermo-reversibility was studied using dynamic laser light scattering, ultrasonic resonator technology and near-infrared (NIR) analytical centrifugation. As a result, the majority of the dispersions were indeed nano-emulsions that exhibited only kinetic stability. Dispersions that were stable following the heat stress test were then further evaluated with respect to an alternative compounding other than dilution from a preconcentrate. Seven dispersions were hereafter deemed to be stable in the thermodynamic sense because they exhibited the same light scattering results independent of their compounding method. In conclusion, the proposed stability categories were shown to successfully assign dispersions. This has a general importance and can, for example, be applied when nano-dispersions are used as pre-clinical formulations.
以纳米液滴形式分散在水中的脂质制剂具有相当大的药物学兴趣。然而，最近有一场关于哪种系统形成稳定的溶胀胶束而不是其他热力学不稳定的纳米乳剂的争论。本研究通过考虑粒径和多分散性的理论论点，为纳米分散体引入了稳定性类别。在第二步中，研究了 20 种制药纳米乳剂制剂相对于水相分散体的物理稳定性。使用动态激光光散射、超声谐振器技术和近红外（NIR）分析离心法研究了热可逆性。结果表明，大多数分散体确实是纳米乳剂，仅表现出动力学稳定性。在热应力测试后稳定的分散体随后根据除从预浓缩物稀释之外的替代化合物进一步进行评估。此后，有 7 种分散体被认为在热力学意义上是稳定的，因为它们表现出相同的光散射结果，而与它们的复合方法无关。总之，所提出的稳定性类别成功地分配了分散体。这具有普遍的重要性，例如，当纳米分散体用作临床前制剂时，可以应用。
