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. 2023 Oct 30;24(21):15764. doi: 10.3390/ijms242115764

Table 1.

Advantages and disadvantages of preparation methods of LNPs.

Methods Advantages Disadvantages
Hot High-Pressure Homogenization Large scale production, absence of organic solvent, incorporation of lipophilic and insoluble drugs Temperature dependent degradation, intricacy of crystallization, unsuitable for heat-sensitive or hydrophilic drugs
Cold High-Pressure Homogenization Suitable method for thermolabile compounds Large particle size and broader size distribution
Ultrasonication Common laboratory equipment Wider size distribution, large amount of surfactant required, physical instability
Phase Inversion Temperature Temperature can be reduced by surfactant incorporation, narrow size distribution, high stability Thermolabile ingredients degradation
Precipitation Rapid and reproducible Toxicological issues due to solvent residue
Coacervation Simple, avoidance of organic solvent Applicable only to non-pH dependent drugs and alkaline nature lipids
Microemulsion Scale up method, thermodynamically stable formulation Multiple steps involved, diluted dispersion acquired
Double Emulsion Applicable to hydrophilic drugs Large particle size, low entrapment efficiency and drug loading
Emulsification High encapsulation efficiency, low energy input, no thermal stress Removal of organic solvent
Thin Film Hydration MLVs are prepared, good reproducibility Low encapsulation efficiency
Proliposome High encapsulation efficiency, fast, simple, large quantity production Poor reproducibility
Ether/Ethanol Injection Simple, large quantity production,
reproducible
Removal of organic solvent, poor encapsulation (in case of ethanol injection method)
Solvent Evaporation Avoidance of heat Solvent residue may cause toxicological problems, dilute suspension
Solvent Injection Easy and fast, small droplets Residual solvent, removal of organic solvent
Microfluidization Laboratory and industrial scale method High amount of solvent residue
Self-emulsifying system Enhanced solubility, prevent the biodegradation of lipophilic drugs Low drug loading capacity, drug leakage, low stability