FORMULATIONS FOR CATHEPSIN K INHIBITORS
The instant invention relates to pharmaceutical compositions comprising cathepsin K inhibitors as the active ingredient with excipients which include binders, diluents, lubricants, and disintegrants. Also disclosed are processes for making said pharmaceutical compositions for oral and intravenous delivery.
1 . A pharmaceutical composition comprising by weight, about 0.5 to 40% by weight of a cathepsin K inhibitor, or a pharmaceutically acceptable salt thereof, and from about 60% to 99.5% by weight of excipients selected from diluents, a binder, a lubricant, and a disintegrant.
2 . The pharmaceutical composition of claim 1 wherein the cathepsin K inhibitor is N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide, or a pharmaceutically acceptable salt thereof.
3 . The pharmaceutical composition of claim 2 wherein the diluents are selected from the group consisting of lactose anhydrous, lactose monohydrate, mannitol, microcrystalline cellulose, calcium phosphate and starch; the binder is hydroxypropyl cellulose, polyvinylpyrrolidone or hydroxypropylmethylcellulose; the lubricant is magnesium stearate or sodium stearyl fumerate; and the disintegrant is croscarmellose sodium, starch or sodium starch glycolate.
4 . The pharmaceutical composition of claim 3 wherein the diluents are lactose monohydrate and microcrystalline cellulose; the binder is hydroxypropyl cellulose; the lubricant is magnesium stearate; and the disintegrant is croscarmellose sodium.
5 . A pharmaceutical composition comprising by weight, about 0.5 to 40% by weight of a cathepsin K inhibitor, or a pharmaceutically acceptable salt thereof, and from about 60% to 99.5% by weight of excipients selected from diluents and a lubricant.
6 . The pharmaceutical composition of claim 5 wherein the cathepsin K inhibitor is N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide, or a pharmaceutically acceptable salt thereof.
7 . The pharmaceutical composition of claim 6 wherein the diluents are selected from the group consisting of lactose anhydrous, lactose monohydrate, mannitol, microcrystalline cellulose, calcium phosphate and starch; and the lubricant is magnesium stearate or sodium stearyl fumerate.
8 . The pharmaceutical composition of claim 7 wherein the diluents are lactose monohydrate and microcrystalline cellulose; and the lubricant is magnesium stearate.
9 . The pharmaceutical composition of claim 5 which also contains a binder.
10 . The pharmaceutical composition of claim 9 wherein the binder is hydroxypropyl cellulose, polyvinylpyrrolidone or hydroxypropylmethylcellulose.
11 . The pharmaceutical composition of claim 10 wherein the binder is hydroxypropyl cellulose.
12 . An intravenous pharmaceutical composition comprising N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide, or a pharmaceutically acceptable salt thereof, water, a modified cyclodextrin and a wetting agent.