Effect of Cryoprotectant and Freeze-Drying Process on the Stability of W/O/W Emulsions

Abstract

In order to protect a hydrophilic drug and to prolong its further delivery, the formulation of multiple emulsions could be worthy. However, the double emulsions are not stable, their structure can change, leading to the formation of a single emulsion as the destruction of the system, and the drug can release easily from the globules in liquid state. The freeze-drying technology could be used to produce dry emulsion, the powder form being much more stable. The aim of this work was to study the influence of a cryoprotectant and a freeze-drying process on the stability of W/O/W emulsions. Samples were frozen at two different freezing rate (ν _f  = 0.55°C/min and 1.25°C/min) and successively dried at two different sublimation temperature (T _s  = − 10°C and − 20°C). The particle size distributions were measured by granulometer and UV spectrophotometer was performed to investigate the leakage of internal constituent. The glass transition temperature (T _g ) of the double emulsions was analyzed by DSC. The particle sizes became even smaller after freeze drying, except when κ-carrageenan is used as a cryoprotectant. In that case, the particles became aggregated after freeze drying, whatever the process conditions. The mean size is considerably reduced when the globules are diluted at low concentration in glucose and trehalose solution. When the concentration is increased, the size distribution is not significantly affected. The leakage of the internal aqueous phase to the external one during freeze drying was measured as an indicator of the structure stability. It is affected by the nature of the cryoprotectant and the conditions of the freeze-drying process. The leakage of the internal phase was smaller when cycle III (ν _f  = 1.25°C/min, T _s  = − 10°C) was processed. From our experiments, we suppose that the water transfer from the inner phase to the outer aqueous phase results in the diminution of the globules size in double emulsion. The T _g of the double emulsions diluted with trehalose and glucose were determined at − 33.8°C and − 47.1°C. In contrast, the T _g of double emulsion with κ-carrageenan and HES did not appear.

Keywords:

• Cryoprotectant
• Freeze drying
• Freezing rate
• Stability
• Sublimation temperature
• W/O/W emulsions

Notes

¹The major peak.

²Secondary peak.

³Ternary peak.