title: 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 (dh) = 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 dh and PDI values of the fresh micelle formulation.
authors.affiliation: Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, University of Zagreb , Zagreb , Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pepić
authors.forename: Jasmina
authors.initials: J
authors.lastname: Lovrić
authors.forename: Anita
authors.initials: A
authors.lastname: Hafner
authors.forename: Jelena
authors.initials: J
authors.lastname: Filipović-Grčić
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004355:Drug Stability; D008823:Micelles; D020442:Poloxamer / Q000737:chemistry*; D011208:Powders; D013696:Temperature
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011208:Powders; D020442:Poloxamer
keywords: Mixed Pluronic micelles; Pluronic F127; Pluronic L121; powder form; stability