Table 5.

Pros and cons of different lipid nanoparticles production.

Methods	Advantages	Disadvantages
Hot HPH	versatile, avoid organic solvent, easy scalability, and short production time	high temperature can cause degradation, conformational changes in protein, changes in particle size (coalescence of particles), burst release due to high emulsifiers concentration
Cold HPH	avoid thermal exposure of the drug; good for temperature-labile drugs or hydrophilic drugs	higher Polydispersity index (PDI)
Microemulsion	no need for specialized equipment (robust) and low energy for production	high concentrations of surfactants and co-surfactants, presence of large amounts of water in the system
Emulsification-solvent evaporation	avoid heat during production thus useful for thermolabile drugs; simple procedure	solvent residues
Emulsification/ultrasound/sonication	no organic solvent residue, no burst release, high lipid concentration, versatile, avoid use of organic solvent, better drug loading than HPH	metallic particle contamination, broader particle size (higher PDI)
Emulsification-solvent diffusion	simple procedure, fast drug release (drawback when slow release is required)	low lipid content, low EE and DL, organic solvent residue, lack of scale-up
Membrane Contactor	simple method, control of particle size by selection of process parameters (size of membrane pores)	limited scaling up possibility