Formulations have been developed to improve the solubility of
corticosteroids such as fluticasone proprionate in a composition designed
to achieve localized release of the drug in the small intestine and/or
colon. In one embodiment, solid dispersions of fluticasone are prepared
wherein the drug is blended with or coated onto a highly water soluble
substrate such as nonpareil (sugar beads) then coated with a layer of
polymer soluble in small intestinal fluid, then coated with an enteric
coating. The inner polymer layer controls release of the drug, and the
enteric coating, a pH sensitive polymer that is broken down in the ileum
and colon, controls localized release of drug at various sites within the
gastrointestinal tract. The multilayer pharmaceutical composition can be
in the form of pellets, tablets compressed from pellets or pellets packed
into capsules. The release profile of the drug can be manipulated by (1)
altering size or shape (i.e., surface area) and solubility of the inert
substrate; (2) the ratio of drug to polymer, the polymer composition and
solubility, the porosity of the polymer; (3) the drug form (i.e., free
base or salt, or which salt); and the thickness and/or surface area of
the drug/polymer and/or enteric coating. In a preferred embodiment, the
composition is administered orally. This may also be packaged to provide
for an escalating or tapering dosage.