Formulations of (+)-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-4-acetylaminoisoindoline-1,3-dione
Pharmaceutical compositions and single unit dosage forms of (+)-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-4-acetylaminoisoindoline-1,3-dione, or a pharmaceutically acceptable stereoisomer, prodrug, salt, solvate, hydrate, or clathrate thereof, are provided herein. Also provided are methods of treating, managing, or preventing various diseases or disorders.
1 . A pharmaceutical composition in the form of an oral tablet comprising:
a) a core composition, wherein the core composition comprises compound A:
or a pharmaceutically acceptable salt thereof, a filler, a disintegrant, and a lubricant, wherein the filler comprises i) lactose monohydrate in an amount of 50% to 65% by weight of the pharmaceutical composition and ii) cellulose in an amount of 15% to 40% by weight of the pharmaceutical composition, and
b) a coating formulation comprising polyvinyl alcohol,
wherein the coating formulation does not contain medium chain triglycerides (MCTs) and no color fading of the tablet is observed at 48 hours when placed in an open dish stability chamber maintained at 40° C. and 75% relative humidity.
2 . The pharmaceutical composition of claim 1 , wherein compound A is present in an amount of 5% to 25% by weight of the pharmaceutical composition.
3 . The pharmaceutical composition of claim 1 , wherein the disintegrant is croscarmellose.
4 . The pharmaceutical composition of claim 3 , wherein the croscarmellose is present at an amount of 2% to 8% by weight of the pharmaceutical composition.
5 . The pharmaceutical composition of claim 3 , wherein lactose monohydrate is present at an amount of 60% by weight of the core composition and the croscarmellose is present at an amount of 2% to 8% by weight of the core composition.
6 . The pharmaceutical composition of claim 1 , wherein the lubricant is magnesium stearate.
7 . The pharmaceutical composition of claim 6 , wherein the magnesium stearate is present at an amount of 0.25% to 5% of the pharmaceutical composition.
8 . The pharmaceutical composition of claim 1 , wherein the polyvinyl alcohol is present in an amount of 35% to 45% by weight of the coating formulation.
9 . The pharmaceutical composition of claim 1 , wherein the coating formulation comprises one or more further excipients, wherein the excipient is a coating agent, a binder, a lubricant, a stabilizing agent, a plasticizer, an adhesive, a glidant, a diluent, or a combination thereof.
10 . The pharmaceutical composition of claim 9 , wherein the excipient is polyethylene glycol.
11 . The pharmaceutical composition of claim 10 , wherein the polyethylene glycol is present in an amount of 20% to 25% by weight of the coating formulation.
12 . The pharmaceutical composition of claim 9 , wherein the excipient is talc.
13 . The pharmaceutical composition of claim 12 , wherein the talc is present in an amount of 10% to 15% by weight of the coating formulation.
14 . The pharmaceutical composition of claim 9 , further comprising one or more coloring agents.
15 . The pharmaceutical composition of claim 14 , wherein the coloring agents are present in an amount of 25% to 30% by weight of the coating formulation.
16 . The pharmaceutical composition of claim 1 , wherein the core composition comprises:
(i) compound A or a pharmaceutically acceptable salt thereof, in an amount of 10% by weight of the core composition;
(ii) lactose monohydrate in an amount of 60% by weight of the core composition;
(iii) microcrystalline cellulose in an amount of 26.25% by weight of the core composition;
(iv) croscarmellose in an amount of 3% by weight of the core composition; and
(v) magnesium stearate in an amount of 0.75% by weight of the core composition.
17 . The pharmaceutical composition of claim 16 , wherein the coating formulation comprises:
(i) polyvinyl alcohol in an amount of 40% by weight of the coating formulation;
(ii) polyethylene glycol in an amount of 20% by weight of the coating formulation;
(iii) talc in an amount of 15% by weight of the coating formulation; and
(iv) a mixture of coloring agents in an amount of 25% by weight of the coating formulation.
18 . A method of treating a disease or disorder in a patient, the method comprising administering to the patient the pharmaceutical composition of claim 1 , wherein the disease or disorder is selected from the group consisting of psoriasis, arthritis, dermatitis, acne, dermatomyositis, and ulcerative colitis, Behcet's disease, Crohn's disease, sarcoidosis, uveitis, rosacea and lichen planus.
19 . The method of claim 18 , wherein the psoriasis is plaque-type psoriasis.
20 . The method of claim 18 , wherein the arthritis is psoriatic arthritis.
21 . The method of claim 18 , wherein the disease is Behcet's disease.