Powder form and stability of Pluronic mixed micelle dispersions for drug delivery applications

Abstract

The aim of this work was to optimize a formulation of the Pluronic® F127/L121 mixed micelle system and evaluate it in terms of stability upon dilution in biologically relevant media and to explore the possibility of preparing F127/L121 micelles in a powder form that can be simply reconstituted to an initial freshly made mixed micelle formulation. The mixed F127/L121 micelles were prepared at a relatively high concentration of Pluronics (1% w/w for both Pluronics) using two different methods (direct dissolution and film rehydration) with an external input of energy. The optimal preparation of the mixed F127/L121 micelles (hydrodynamic diameter (d_h) = 75 nm, polydispersity index (PDI) = 0.287) was achieved using the film rehydration method followed by ultrasonication. Stability studies of the F127/L121 micelle system were performed at 25 °C and 37 °C and upon dilution in different biologically relevant media. The F127/L121 micelles were stable in phosphate buffered saline (PBS) upon 100-fold dilution for at least 10 d and in PBS containing bovine serum albumin upon 10 and 50-fold dilution for at least 48 and 12 h, respectively. A dry powdered form of the mixed micelles was prepared by freeze-drying after slow or fast freezing process. The influence of the type and amount of cryoprotectant on the prevention of F127/L121 micelles aggregation during the freeze-drying and reconstitution processes were evaluated. The use of trehalose (5%, w/w) and sucrose (2.5%, w/w) with slow and fast freezing process, respectively, resulted in a reconstituted product with mostly similar d_h and PDI values of the fresh micelle formulation.

• Mixed Pluronic micelles
• Pluronic F127
• Pluronic L121
• powder form
• stability