Solubilization of a Poorly Soluble Aromatic Drug by Micellar Solutions of Amphiphilic Block Copoly(oxyalkylene)s*

This chapter is a summary of our work on the design of block copolymer micellar systems with improved solubilization capacity for poorly soluble aromatic drugs. The copolymers of interest are block copoly(oxyalkylene)s with linear dior triblock architecture which combine hydrophilic poly(ethylene oxide) with hydrophobic blocks formed from poly(propylene oxide), poly(1,2-butylene oxide), poly(styrene oxide) or poly(phenyl glycidyl ether). A comparison of the solubilization capacity per gram of hydrophobic block for the model poorly soluble drug griseofulvin shows an increase in solubilization capacity with increase in the hydrophobicity of the core-forming block and the volume of the core of spherical micelles. As a consequence of their larger core diameter, diblock copolymers are more effective solubilizers than triblock copolymers of similar composition and chain length. Copolymers with short hydrophilic blocks relative to the length of the hydrophobic block may form cylindrical or worm-like micelles of high aggregation number resulting in an increased solubilizing capacity. The formulation of mixed block copolymer systems of high solubilization capacity and favorable gelation characteristics for use in controlled drug delivery is discussed.