Alternatives to using sugars like sucrose or trehalose for lyophilizing 15% TPGS polymeric micelles include other carbohydrates, sugar alcohols, polymers, and cyclodextrins

. The best choice depends on the specific micelle formulation, the drug payload, and your required cake properties and reconstitution time.

Alternative carbohydrates

• Maltose: This is a disaccharide like sucrose and trehalose. It can serve a similar function by forming a glassy matrix to prevent aggregation and maintain micelle structure during freeze-drying.
• Raffinose: As an oligosaccharide, raffinose can also act as a non-reducing carbohydrate lyoprotectant to stabilize nanoparticles.

Polyols

• Mannitol and sorbitol: These sugar alcohols can prevent micelle aggregation and promote easy reconstitution. However, unlike amorphous sugars, they crystallize during freeze-drying and must be used with caution. A common strategy is to combine them with an amorphous excipient like a sugar to create a sturdy cake structure.
• Glycerol: This is a polyol cryoprotectant that can be used to stabilize micelle structures, but it is better for liquid freezing protocols rather than lyophilization, as it is difficult to remove and has a low glass transition temperature.

Polymers

• Polyethylene glycol (PEG): Certain molecular weights of PEG can be used to stabilize micelles by preventing aggregation through steric hindrance. This effect is particularly useful for PEG-based block copolymer micelles where the PEG chain can extend from the surface to repel other particles.
• Hydroxyethyl starch (HES): A large, non-penetrating synthetic polymer, HES can increase the viscosity of the freezing medium and protect the micelles from mechanical stress during lyophilization.
• Poly(vinylpyrrolidone) (PVP): This polymer is a traditional excipient with anti-fouling properties. It stabilizes micelle suspensions by steric repulsion, which helps prevent aggregation.

Cyclodextrins

• Hydroxypropyl-β-cyclodextrin (HPβCD): Often used in pharmaceutical formulations, HPβCD can provide excellent cryoprotection for certain micelle systems. Studies on other polymeric micelles have shown HPβCD to be an effective choice for stabilizing micelles during lyophilization.

Screening for the best alternative

Because TPGS micelles can be sensitive to formulation changes, a screening process is necessary to identify the best cryoprotectant for your specific product.

Hi!

Other than those.. Sucrose can be an another option as it serve as an effective cryoprotectant for lyophilizing 15% TPGS micelles, it forms an amorphous glassy matrix and minimizes micelle destabilization.

Glycine is another option, providing cryoprotection by reducing ice-induced stress during freeze-drying.

Reference in support:

https://doi.org/10.1016/S0378-5173(00)00423-3

https://doi.org/10.1016/0378-5173(90)90231-R

Katherine Hermida

Lyophilization is the sublimation of a solvent (water). All proposed cryoprotectants reduce the temperature at which a dispersed system transforms into a crystalline structure.

It's not clear from your question what you're trying to improve.