Solubilisation of drugs in micellar solutions of diblock copolymers of ethylene oxide and styrene oxide.

The solubilisation of two poorly soluble drugs, furosemide and nabumetone, in micellar solutions of diblock copolymers of ethylene oxide and styrene oxide has been studied at 25 and 37 degrees C and solubilisation capacities compared with published values for griseofulvin and docetaxel. Solubilisation in the micelle core, corrected for the different proportions of poly(styrene oxide) in the copolymers, was similar for all four drugs. The highest solubilisation capacities were found for a copolymer with worm-like micelles.

Solubilisation in aqueous micellar solutions of block copoly(oxyalkylene)s.

The solubilisation capacities of micellar solutions of diblock and triblock copolymers composed of hydrophilic poly(ethylene oxide) and hydrophobic poly(styrene oxide) have been compared using the poorly water-soluble drug griseofulvin as a model solubilisate. Our results showed an increase of solubilisation capacity (expressed as mg griseofulvin per gram of hydrophobic block) with temperature and, for spherical micelles, with core volume before reaching limiting values. A change of micelle shape from spherical to cylindrical (or worm-like) resulting from an increase in micelle aggregation number was accompanied by a further enhancement of solubilisation capacity. Comparison with the solubilisation of the same drug in micellar solutions of block copolymers of poly(ethylene oxide) and poly(1,2-butylene oxide) showed that the solubilisation capacity of a poly(styrene oxide) block was approximately four times that of a poly(1,2-butylene oxide) block for spherical micelles. Solubilisation capacity at 25 degrees C was approximately doubled when griseofulvin was incorporated into a copolymer melt and micelles initially formed from the drug-loaded melt at 65 degrees C rather than by loading the drug into pre-micellised solution at 25 degrees C in the usual manner.

Association properties of ethylene oxide/styrene oxide diblock copolymer E17S8 in aqueous solution.

Ethylene oxide and styrene oxide were sequentially polymerized to form the diblock copolymer E(17)S(8) (E = oxyethylene, OCH(2)CH(2); S = oxyphenylethylene, OCH(2)CH(C(6)H(5)); subscripts denote number-average block lengths in repeat units). Light scattering was used to investigate the properties of the micelles formed in dilute solution in the temperature range 15-30 degrees C. The micelles are elongated (probably spheroidal) at the lower temperature and highly elongated (cylindrical, probably wormlike) at the higher temperature. Comparison with results reported for the copolymer E(11)B(8) (B = oxybutylene, OCH(2)CH(C(2)H(5))) allowed exploration of the effect of changing the hydrophobic block. The results provide useful indicators toward the design of ES copolymers with optimal solubilization properties.