US 6,123,964 A · Wet granulation formulation of a growth hormone secretagogue

Abstract

The present invention relates to a pharmaceutical composition and a process for the preparation of a tablet containing a growth hormone secretagogue as the active ingredient. The tablet is prepared by forming a powder blend of the active ingredient N-[1(R)-[(1,2-dihydro-1-methanesulfonyl-spiro[3H-indole-3,4'-piperdin]-1'- yl)carbonyl]-2-(phenylmethyl-oxy)ethyl]-2-amino-2-methyl-propanamide, or a pharmaceutically acceptable salt thereof, in particular the methanesulfonate salt, with a binder/diluent, a first diluent, a second diluent, a first portion of a disintegrant, and a lubricant; wet granulating the powder blend with a solution of ethanol/water to form granules; drying the granules to remove the ethanol/water; adding a second portion of a disintegrant; lubricating the granules; and compressing the dried granules into the desired tablet form. The present invention further relates to a novel amorphous form of the compound N-[1(R)-[(1,2-dihydro-1-methanesulfonyl-spiro[3H-indole-3,4'-piperdin]-1'- yl)carbonyl]-2-(phenylmethyl-oxy)ethyl]-2-amino-2-methylpropanamide methanesulfonate which is produced directly as a result of the process of tablet formulation.

Claims28

Dependent claims

A pharmaceutical composition comprising:

0.1 to 50% by weight of an active ingredient N-[1(R)-[(1,2-dihydro-1-methanesulfonylspiro[3H-indole-3,4'-piperdin]-1'-y l)carbonyl]-2-(phenylmethyloxy)ethyl]-2-amino-2-methyl-propanamide, or a pharmaceutically acceptable salt thereof;
20 to 40% by weight of a binder/diluent which is selected from:
hydroxypropyl methylcellulose, hydroxypropyl cellulose, pregelatinized starch and polyvinylpyrrolidone;
10 to 20% by weight of a first diluent which is selected from:
lactose, microcrystalline cellulose, calcium phosphate dibasic, mannitol, powdered cellulose and pregelatinized starch;
20 to 50% by weight of a second diluent which is selected from:
lactose, microcrystalline cellulose, calcium phosphate dibasic, mannitol, powdered cellulose and pregelatinized starch;
5 to 15% by weight of a disintegrant which is selected from microcrystalline or croscarmellose sodium;
and
0.05 to 5% by weight of a lubricant which is selected from magnesium stearate, calcium stearate, and steric acid;
wherein sum of the above proportions of the active ingredient, the binder/diluent, the first diluent, the second diluent, the disintegrant, and the lubricant are not greater than 100% by weight.

8 more elements

A pharmaceutical composition comprising:

about 1 to 30% by weight of an active ingredient N-[1-(R)-[(1,2-dihydro-1-methanesulfonylspiro[3H-indole-3,4'-piperdin]-1'- yl)carbonyl]-2-(phenylmethyloxy)ethyl]-2-amino-2-methyl-propanamide, or a pharmaceutically acceptable salt thereof;
about 20 to 40% by weight of pregelatinized starch;
about 10 to 20% by weight of microcrystalline cellulose;
about 20 to 50% by weight of calcium phosphate dibasic;
about 5 to 15% by weight of croscarmellose sodium;
and
about 0.05 to 5% by weight of magnesium stearate,
wherein the sum of the above proportions of active ingredient, pregelatinized starch, microcrystalline cellulose, calcium phosphate dibasic, croscarmellose sodium, and magnesium stearate are not greater than 100% by weight.

5 more elements

A process for the preparation of a tablet containing an active ingredient of the compound:

N-[1(R)-[(1,2-dihydro-1-methanesulfonylspiro[3H-indole-3,4'-piperdin]-1'-y l)carbonyl]-2-(phenylmethyloxy)ethyl]-2-amino-2-methylpropanamide, or a pharmaceutically acceptable salt thereof, comprising the steps of:
(1) forming a powder blend of the active ingredient with a binder/diluent, a first diluent, a second diluent, and a first portion of a disintegrant,
(2) wet granulating the powder blend with a solution of ethanol/water to form granules,
(3) drying the granules to remove the ethanol/water,
(4) adding a second portion of a disintegrant;
(5) lubricating the granules;
and
(6) compressing the dried granules into a desired tablet form.

5 more elements

Dependencies are inferred from the claim text.

Wet granulation formulation of a growth hormone secretagogue

Life of this patent

Wet granulation formulation of a growth hormone secretagogue

Life of this patent

Abstract

Claims28