Immunomodulatory compositions
Immunomodulator formulations for use in the treatment of disease of the GI tract. The formulations comprise a hydroxylase inhibitor and/or an immunosuppressant. Exemplary formulations comprise hydralazine as a hydroxylase inhibitor and/or cyclosporin A as an immunosuppressant.
1. An oral pharmaceutical composition comprising hydralazine and cyclosporin A in a weight ratio (hydralazine:cyclosporin A) of from 0.8:1 to 5:1, wherein the composition is a multiple minibead composition and the hydralazine and cyclosporin A are contained in the minibeads, each minibead comprising a water-soluble polymer matrix material and, dispersed within the matrix material, a hydrophobic phase, the matrix material comprising the hydralazine and the cyclosporin A being dissolved in the hydrophobic phase, at least some of the minibeads having a controlled release coating adapted for the coated minibeads to release hydralazine and cyclosporin A in at least the colon.
2. The pharmaceutical composition of claim 1 wherein the weight ratio is from 0.8:1 to 2:1.
3. The pharmaceutical composition of claim 2 wherein the weight ratio is from 1:1 to 2:1.
4. The pharmaceutical composition of claim 1 which is a for oral administration.
5. The pharmaceutical composition of claim 1 wherein the matrix material comprises a hydrophilic surfactant having an HLB value of at least 15 and the hydrophobic phase comprises a non-ionic surfactant having an HLB value of at least 10 but less than that of the hydrophilic surfactant.
6. The pharmaceutical composition of claim 1 wherein the coated minibeads are coated with a coating comprising a pH independent polymer and a polymer specifically susceptible of degradation by bacterial enzymes in the colon.
7. The pharmaceutical composition of claim 6 wherein the pH independent polymer is ethylcellulose and the polymer specifically susceptible of degradation by bacterial enzymes in the colon is a polysaccharide.
8. The pharmaceutical composition of claim 1 wherein the minibeads are coated with additional drug layers, wherein the drug layer is part of the coating or independent thereof.