Poloxamines and Poloxamers as Polymeric Micellar Carriers for Simvastatin: Interactions at the Air-Water Interface and in Bulk Solution

A comprehensive analysis of mixed monolayers of simvastatin and several varieties of Pluronic [poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO] and Tetronic (X-shaped PEO-PPO) at the air-water interface was carried Out With the aim of obtaining predictive information about the performance of the mixed systems at bulk, namely, the capability of the micelles to host the drug and the physical stability of the drug-loaded micelles under dilution. pi-A isotherms recorded at the air/HCl interface evidenced negative deviations from ideal behavior for copolymers with short PPO blocks, that is, Pluronic F87 and Tetronic 904, and positive deviations for copolymers with long PPO blocks, that is, Pluronic F 127 and P 123 and Tetronic 1301, 1307, and 150R1. Simvastatin intercalation among the unimers of Pluronic F87 and Tetronic 904 significantly altered the hydrophobic interactions among PO units, which are involved in the micellization process, resulting in worse drug solubilization and poor stabilization of the lactone group and in less stable micelles against dilution. Pluronics F127 and P123 and Tetronics 1301, 1307, and 150R1 rendered micelles that preferentially host the drug in the core-shell interface and call stand up to sudden dilutions, retaining the drug hosted and protecting it from chemical degradation. Tests with copolymers covering a wide range of molecular weights and EO/PO ratios enabled to correlate structural properties with the behavior at the interface and in the bulk solution and with the localization of the drug inside the micelles.