ORAL SUSTAINED RELEASE ANTIDEPRESSANT FORMULATION
Pharmaceutical presentations or phenoxathiin-based MAO-A inhibitors are disclosed whereby the MAO receptors are capable of sustained release in the digestive tract. Particular phenoxathiin-based MAO-A inhibitors include those of the following formula: wherein n is 0, 1 or 2; R 1 is a branched or straight chain C1-5 alkyl or C3-6 cycloalkyl optionally substituted with hydroxyl, or one or more halogens; and X 1 , X 2 , X 3 , X 4 , and X 5 are either all hydrogens or one or two of X 1 , X 2 , X 3 , X 4 , and X 5 are halogen and the remainder are hydrogens, with the proviso that when n is 0 or 1 and each X is hydrogen, R 1 is not methyl. A wide variety or sustained release mechanisms can be utilized so as to provide gradual release of the active ingredient after ingestion as a pharmaceutical presentation, such as a tablet or capsule. Presentations include sustained release tablets, sustained release capsules, capsules containing sustained release beads.
1 . A sustained release oral pharmaceutical product comprising a phenoxathiin-based MAO-A inhibitor of the following formula:
wherein n is 0, 1 or 2; R 1 is a branched or straight chain C1-5 alkyl or C3-6 cycloalkyl optionally substituted with hydroxyl, or one or more halogens; and X 1 , X 2 , X 3 , X 4 , and X 5 are either all hydrogens or one or two of X 1 , X 2 , X 3 , X 4 , and X 5 are halogen and the remainder are hydrogens, with the proviso that when n is 0 or 1 and each X is hydrogen, R 1 is not methyl.
2 . The sustained release product of claim 1 , wherein the phenoxathiin-based MAO-A inhibitor is 3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin 10,10-dioxide.
3 . The sustained release product of claim 1 , wherein said product is a tablet.
4 . The sustained release product of claim 1 , wherein said product is a capsule.
5 . The sustained release product of claim 1 , wherein said product is a core sheathed in an annular body.
6 . The sustained release product of any claim 1 , wherein said product is formulated so as to achieve plasma levels of phenoxathiin-based MAO-A inhibitor ranging from about 40 ng/ml to about 80 ng/ml.
7 . The sustained release product of claim 1 , wherein said product is formulated so as to achieve plasma levels of phenoxathiin-based MAO-A inhibitor ranging from about 10 ng/ml to about 150 ng/ml.
8 . The sustained release product of claim 1 , wherein said product contains 3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin 10,10-dioxide as the sole active ingredient.
9 . The sustained release product of claim 2 , wherein said 3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin 10,10-dioxide is characterized as having a melting point at about 169-175° C.
10 . The sustained release product of claim 2 , wherein said 3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin 10,10-dioxide is characterized as being in crystalline form and having an x-ray powder diffraction peak at 2θ=11.0°, using CuK α radiation.
11 . The sustained release product of claim 1 , wherein said product is a tablet containing about 50 to 500 milligrams of 3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin 10,10-dioxide.
12 . An oral pharmaceutical dosage form comprising 3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin 10,10-dioxide and adapted to retard release of 3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin 10,10-dioxide in the digestive tract.
13 . The oral pharmaceutical dosage form of claim 12 that is a tablet, a capsule, or a core sheathed in an annular body.
14 . The pharmaceutical dosage form of claim 13 that is a tablet.