PHARMACEUTICAL FORMULATIONS
The present invention provides compositions and methods for the treatment or prevention of pulmonary hypertension comprising administering an ascomycin, or a pharmaceutically acceptable salt, solvate, analog, or prodrug thereof to the patient with pulmonary hypertension. Described herein are liquid formulations which deliver an ascomycin. The liquid formulation can be placed in a soft gelatin capsule.
1 . A soft gelatin capsule comprising:
a shell and a liquid fill material wherein the liquid fill material comprises an active agent, or a pharmaceutically acceptable salt, solvate, analog, or prodrug thereof, dissolved in a solvent, wherein the active agent is an ascomycin class compound.
2 . The soft gelatin capsule of claim 1 , wherein the active agent is tacrolimus (FK-506), ascomycin (FK-520), pimecrolimus (33-epi-chloro-33-desoxy-ascomycin), ABT-281, SDZ 281-240, desmethyl ascomycin (FK-523), prolytacrolimus(FK-525), or combinations thereof.
3 . The soft gelatin capsule of claim 1 , wherein the daily dose provides whole blood concentration of about 0.02 ng/mL to about 50 ng/mL.
4 . The soft gelatin capsule of claim 1 , wherein the active agent is tacrolimus, ascomycin, desmethyl ascomycin, or prolyltacrolimus.
5 . The soft gelatin capsule of claim 1 , wherein the solvent is Maisine 35-1, sesame oil, miglyol 812, Capryol 90, Lauroglycol FCC, Span 80, caprylic acid, Transcutol HP, Tween 80 (polysorbate 80), Kolliphor EL (Cremophor EL), labrasol, Vitamin E TPGS, PEG 400, propylene glycol, ethanol, Phosal 50 PG, triethylcitrate, or PEG 3350.
6 . The soft gelatin capsule of claim 5 , wherein the solvent is labrasol, Capmul or combinations thereof.
7 . The soft gelatin capsule of claim 1 , wherein the solvent comprises a surfactant.
8 . The soft gelatin capsule of claim 7 , wherein the surfactant is Caspmul MCM EP, Labrafil M 2125 CS, peceol, Tween 80 (polysorbate 80), Kolliphor EL (Cremophor EL), labrasol, Vitamin E TPGS, or any combination thereof.
9 . The soft gelatin capsule of claim 1 , wherein the solvent further comprises a plasticizer.
10 . The soft gelatin capsule of claim 9 , wherein the plasticizer is triethylcitrate.
11 . The soft gelatin capsule of claim 1 , wherein the solvent comprises labrasol, triethyl citrate, and BHT.
12 . The soft gelatin capsule of claim 1 , which is coated with an enteric coating selected from the group consisting of: ethylcellulose, methacrylic acid copolymer, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, shellac, and any combination thereof.