Table 3 Different types of excipients commonly used as lyoprotectants in freeze-drying of nanoformulations
Excipients as lyoprotectants | Molecular weight (g/mol or kDa) | Optimum concentration of lyoprotectants (% w/w or mM) | Glass transition temperature (Tg, ℃) | Functions | References |
|---|---|---|---|---|---|
Bulking agents | |||||
Glycine | 75.07 | 10 | − 70 to − 90 ℃ | Provide bulk to the formulation, particularly if the product concentration to freeze-dry seems to be very low | |
Hydroxyethyl starch | 670 kDa | 12.5 | 44 ℃ | ||
Lactose | 342.3 | 1–2 | 101 ℃ | ||
Mannitol | 182.18 | 6 | 13 ℃ | ||
Sucrose | 342.3 | 2.5 | − 46 ℃ | ||
Trehalose | 378.33 | 20 | 106 ℃ | [47] | |
Buffers | |||||
Citrate | 192.12 | NA | 105 ℃ | Adjust and maintain pH changes during freezing | [56] |
Histidine | 155.15 | 3.5 mM | − 32 ℃ | ||
Phosphate | 94.97 | 20 mM | NA | [59] | |
Tris HCl | 121.14 | NA | − 81 ℃ | [60] | |
Stabilizers | |||||
Alanine | 89.09 | 1–5 | − 10 to 35 ℃ | Offer protection from freezing and drying stresses during the freeze-drying process | |
Dextran | 40–70 kDa | 2 | 68.2℃ | ||
glycerol | 92.09 | NA | NA | ||
Polyethylene glycol 400 | 380–420 g/mol | 25–35 | − 63 ℃ | ||
Polyvinyl pyrrolidone | NA | 7.5 | NA | ||
Sodium chloride | 58.44 | 5 M | NA | ||
Tonicity adjusters | |||||
Glycine | 75.07 | 10 | − 70 to − 90 ℃ | Produce an isotonic solution while controlling osmotic pressure | |
Glycerol | 92.09 | NA | NA | ||
Mannitol | 182.18 | 6 | 13 ℃ | ||
Sucrose | 342.3 | 2.5 | − 46 ℃ | ||
Sodium chloride | 58.44 | 5 M | NA | ||
Collapse temperature modifiers | |||||
Hydroxypropyl-β-cyclodextrin | 1387 | 5–10 | 418 ℃ | Raise the product's collapse temperature to attain optimal drying temperatures | [65] |