ORAL AND INJECTABLE FORMULATIONS OF TETRACYCLINE COMPOUNDS
Injectable and oral formulations of a tetracycline compound are described. In one embodiment, the invention pertains to an oral formulation of a 9-aminomethyl tetracycline compound, or a salt thereof, in tablet form or capsule. The formulations may be used, for example, to treat infections.
1 . An oral formulation of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof.
2 . The oral formulation of claim 1 , wherein the formulation is in tablet form.
3 . The oral formulation of claim 2 , wherein the formulation comprises about 5-40% weight percent of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline tosylate salt, about 50-90% weight percent of a diluent, about 0.01-0.5% weight percent of a stabilizer, about 0.2-2.0% weight percent of a glidant, about 1-11% weight percent of a lubricant, about 0.5-10% weight percent of a disintegrant, and optionally 0.5-1.5% of an anti-adherent.
4 . The oral formulation of claim 3 , wherein the diluent comprises lactose, microcrystalline cellulose, or a combination thereof.
5 . The oral formulation of claim 3 , further comprising a buffering agent, an antiadherent, a coating component, or a combination thereof.
6 . The oral formulation of claim 2 , wherein the formulation comprises:
about 10-30% weight percent of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof;
about 50-90% weight percent of a diluent;
about 0.01-0.5% weight percent of a stabilizer;
about 0.2-2.0% weight percent of a glidant;
about 3-10% weight percent of a lubricant;
about 3-10% weight percent of a disintegrant, and bout 0.01-0.5% weight percent of an anti-adherent.
7 . The oral formulation of claim 6 , comprising:
about 26-28% weight percent of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline tosylate salt;
about 10-30% weight percent lactose;
about 30-50% weight percent microcrystalline cellulose;
about 0.05-0.35% weight percent sodium bisulfite;
about 0.5-1.5% weight percent silicon dioxide;
about 4.5-6.0% weight percent sodium stearyl fumarate or magnesium stearate;
about 4-6% weight percent crospovidone; and
about 0.5-1.5% weight percent of talc.
8 . The oral formulation of claim 7 , consisting of:
about 26-28% weight percent of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline, tosylate salt;
about 15-25% weight percent lactose;
about 35-45% weight percent microcrystalline cellulose;
about 0.15-0.25% weight percent sodium bisulfite;
about 0.8-1.2% weight percent silicon dioxide;
about 4.8-5.2% weight percent sodium stearyl fumarate or magnesium stearate;
about 4.8-5.2% weight percent crospovidone;
about 0.15-0.25% weight percent talc and
about 3-5% of OPADRY® AMB Red.
9 . The oral formulation of claim 1 , wherein the formulation comprises about 90-250 mg of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof.
10 . The oral formulation of claim 9 , wherein the formulation is in the form of a tablet, and wherein the tablet consists essentially of:
about 125-140 mg of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline, tosylate salt; about 90-110 mg lactose;
about 200-220 mg microcrystalline cellulose;
about 0.75-1.5 mg sodium bisulfite;
about 20-30 mg crospovidone;
about 2-3 mg silicon dioxide;
about 20-30 mg magnesium stearate;
about 4.5-5.5 mg talc and
about 20-40 mg of OPADRY® AMB Red.
11 . The oral formulation of claim 1 , comprising 90-180 mg of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline free base and a pharmaceutically acceptable carrier.
12 . The oral formulation of claim 2 , wherein the oral formulation is compressed using direct compression, roller compaction, or a combination thereof.
13 . The oral formulation of claim 12 , wherein the 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof is present in an amount of more than 10% by weight based on the total weight of the formulation.
14 . A compressed solid dosage form comprising 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof and at least one pharmaceutically acceptable diluent, wherein the 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof is present in an amount that is about 20% by weight based on the total weight of the compressed solid dosage form.
15 . An injectable formulation comprising about 90-110 mg of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline free base and a pharmaceutically acceptable carrier.
16 . The injection formulation of claim 15 , wherein the formulation further comprises one or more components selected from a lyoprotectant, an anti-oxidant, and a pH adjustment compound.
17 . The injectable formulation of claim 16 , wherein the formulation consists essentially of about 100 mg of 9-[(2,2-dimethylpropyl amino)-methyl]-minocycline free base, 100 mg of sucrose, 1 mg of sodium bisulphite, pH adjustment compounds and an aqueous carrier.
18 . A method for treating an infection in a subject, comprising administering to the subject an effective amount of the formulation of claim 1 .
19 . A method for preparing a pharmaceutical formulation comprising granulating the oral formulation according to claim 1 to form granules, followed by shaping the granules into an oral dosage form, wherein the oral formulation further comprises about 50-90% weight percent of a diluent, about 0.01-0.5% weight percent of a stabilizer, about 0.2-2.0% weight percent of a glidant, about 1-11% weight percent of a lubricant, and about 0.5-10% weight percent of a disintegrant.
20 . The method of claim 19 , wherein the granulating comprises roller compaction, and wherein the granules comprise greater than 10% weight percent of 9-[(2,2-dimethylpropyl amino)-methyl]-minocycline.