Back to results
US 2011/0237609 A1Published application
Antifolate compositions
AssigneeChelsea Therapeutics, Inc.
InventorHarish K. Pimplaskar
Life of this patent
Estimating the term…
Abstract
The present invention provides pharmaceutical compositions comprising an antifolate compound. The compositions can be prepared such that unit dosages of the composition exhibit excellent API content uniformity, such as by wet granulation or hot melt granulation. The pharmaceutical compositions are useful in the treatment of multiple conditions, including abnormal cell proliferation, inflammatory diseases, asthma, and arthritis.
Claims79
A pharmaceutical composition comprising:
- about 0.01% to about 20% by weight of an antifolate compound according to Formula (6):
- wherein:
- X is CHR8 or NR8;
- Y1, Y2, and Y3 independently are O or S;
- V1 and V2 independently are O, S, or NZ;
- Z is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl;
- R1 and R2 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl;
- R3 is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, hydroxyl, or halo;
- and
- R4, R5, R6, R7, and R8 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, acyl, —C(O)-alkyl, —C(O)-alkenyl, or —C(O)-alkynyl;
- or a pharmaceutically acceptable ester, amide, salt, solvate, enantiomer, or prodrug thereof;
- about 25% to about 95% by weight of at least one filler;
- about 1% to about 10% by weight of at least one disintegrant;
- and
- about 0.1% to about 5% by weight of at least one lubricant.
12 more elements
A pharmaceutical composition comprising:
- an alkali metal salt of (S)-2-{-4-[2-(2,4-diamino-quinazolin-6-yl)-ethyl]-benzoylamino}-4-methylene-pentanedioic acid, wherein the compound exhibits an enantiomeric purity for the (S) enantiomer of at least about 95%;
- and
- at least one excipient selected from the group consisting of fillers, disintegrants, and lubricants;
- wherein the composition is provided as a group of individual unit dosages and the % RSD of the content of the antifolate compound in the group of individual unit dosages is less than about 5%.
1 more element
A method of making a pharmaceutical composition comprising an antifolate compound according to Formula (6):
- wherein:
- X is CHR8 or NR8;
- Y1, Y2, and Y3 independently are O or S;
- V1 and V2 independently are O, S, or NZ;
- Z is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl;
- R1 and R2 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl;
- R3 is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, hydroxyl, or halo;
- and
- R4, R5, R6, R7, and R8 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, acyl, —C(O)-alkyl, —C(O)-alkenyl, or —C(O)-alkynyl;
- or a pharmaceutically acceptable ester, amide, salt, solvate, enantiomer, or prodrug thereof;
- the method comprising wet granulating about 0.01% to about 20% by weight of the antifolate compound with about 25% to about 95% by weight of at least one filler, about 1% to about 10% by weight of at least one disintegrant;
- and about 0.1% to about 5% by weight of at least one lubricant.
9 more elements
A method of making a pharmaceutical composition comprising an antifolate compound according to Formula (6):
- wherein:
- X is CHR8 or NR8;
- Y1, Y2, and Y3 independently are O or S;
- V1 and V2 independently are O, S, or NZ;
- Z is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl;
- R1 and R2 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl;
- R3 is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, hydroxyl, or halo;
- and
- R4, R5, R6, R7, and R8 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, acyl, —C(O)-alkyl, —C(O)-alkenyl, or —C(O)-alkynyl;
- or a pharmaceutically acceptable ester, amide, salt, solvate, enantiomer, or prodrug thereof;
- the method comprising hot melt granulating about 0.01% to about 20% by weight of the antifolate compound with about 25% to about 95% by weight of at least one filler, about 5% to about 50% by weight of a polyglycolized glyceride;
- and about 0.1% to about 5% by weight of a lubricant.
9 more elements
A pharmaceutical composition comprising:
- about 0.01% to about 20% by weight of an antifolate compound according to Formula (6):
- wherein:
- X is CHR8 or NR8;
- Y1, Y2, and Y3 independently are O or S;
- V1 and V2 independently are O, S, or NZ;
- Z is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl;
- R1 and R2 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl;
- R3 is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, hydroxyl, or halo;
- and
- R4, R5, R6, R7, and R8 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, acyl, —C(O)-alkyl, —C(O)-alkenyl, or —C(O)-alkynyl;
- or a pharmaceutically acceptable ester, amide, salt, solvate, enantiomer, or prodrug thereof;
- about 25% to about 95% by weight of at least one filler;
- about 5% to about 50% by weight of a polyglycolized glyceride;
- and
- about 0.1% to about 5% by weight of a lubricant.
12 more elements
Dependencies are inferred from the claim text.