Phase Inversion Temperature

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Several methods have been used in lipid nanoparticles (LNPs) production. Among developed approaches for the preparation of lipid nanoparticles, low-energy approaches give the possibility to develop LNPs without high shear and pressure. Recently, the phase inversion temperature (PIT) has become a hot spot for producing LNPs, especially nanoemulsions. Creative Biolabs has rich experience in this field and is willing to provide professional services to our customers.

Introduction of Phase Inversion Temperature

The PIT is mainly based on the specific solubility of nonionic surfactants at different temperatures. The nonionic surfactant exhibits hydrophilicity at low temperatures, while it becomes lipophilic at high temperatures. However, in the process of changing from hydrophilic properties to lipophilic properties, there was a temperature that showed neither lipophilicity nor hydrophilicity. The temperature is called PIT. With this method, an emulsion inversion from oil-in-water (O/W) macro-emulsion to a water-in-oil (W/O) emulsion, then the O/W nanoemulsion was formated while cooling. Furthermore, nanoemulsions produced by the PIT method have the advantages of low solubility, low-viscous, fine disperse emulsion concentrates, and the nanoemulsions can be diluted with maintaining their fine dispersity and long-term stability.

Schematic view of phase inversion temperature.Fig.1 Schematic view of phase inversion temperature. (Saffarionpour, 2019)

Phase Inversion Temperature for LNPs Development

In the last decades, many carriers have been proposed for drug delivery, LNPs are one of the most widely used carriers. Compared with other systems, LNPs present the advantages of improving drug stability, increasing bioavailability, incorporating drugs with different properties. The PIT method has been explored to prepare LNPs for many years. This method will get LNPs with small particle size, good stability, and good loading capacity. The PIT method is particularly promising because it is an organic solvent-free and low-energy method. In addition, the process of PIT is simple and low-energy consuming, it is easy industrial scale-up.

Previous studies have shown that LNPs obtained from the PIT method may improve the stability and increase the bioavailability of the beta-carotene. Moreover, the encapsulated vitamin D within LNPs generally improved bioavailability. More importantly, protein nanoparticles can be formed by the PIT way. This approach offers an alternative to existing methods of fabricating protein nanoparticles and microparticles used in different industries. Even though numerous ways have been reported for the preparation of LPs, the PIT process is the most preferred one, as there is no organic solvent involved in the preparation process.


  • Lower diameter with higher emulsification efficiency
  • Without organic solvent
  • Simple process and low consumption
  • Easy industrial production

Based on the above advantages, the preparation of LNPs for encapsulation of different drugs applying low-energy methods is considered a newly emerging approach. If necessary, please contact us to get the most suitable service for your project.


  1. Saffarionpour, S. Preparation of Food Flavor Nanoemulsions by High- and Low-Energy Emulsification Approaches. Food Engineering Reviews 2019, 11: 259-289.
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