Stable, high dose, high bulk density ibuprofen granulations for tablet and capsule manufacturing

Claim 2

A phamaceutical, high drug content ibuprofen dry granulation formulation composition comprising (a) about 85 to 99 percent, W/W of ibuprofen (b) about 1 to 15 percent of croscarmellose sodium NF, types A and/or B, the percentages of each ingredient (a) and (b) being based upon the weight of the total granulate formulation.

Claim 3

An ibuprofen granulation formulation according to claim 1 which further includes from 0.4 to 1 percent of colloidal silicon dioxide NF, based upon the weight of the total granulation formulation.

Claim 4

An ibuprofen granulation formulation according to claim 1 prepared by (1) dry mixing (a) ibuprofen and (b) croscarmellose sodium NF containing mixture to an essentially uniform consistency, (2) roller compacting or slugging the mixture from step (1), and (3) sizing the compacted or slugged mixture from step (2) to form a granular ibuprofen composition.

Claim 5

A pharmaceutical granulation composition useful for making therefrom extensive numbers of ibuprofen containing compressed tablets or filled pharmaceutical capsules having dosage ranges of from about 100 to 1200 mg. of ibuprofen per compressed tablet or filled capsule which comprises (A) a granulate formulation containing ibuprofen and croscarmellose sodium type A as described in claims 1 or 2 and optionally mixed with the following extragranular part (B) ingredients: ______________________________________ Mg. per tablet or Ingredient capsule dosage unit ______________________________________ Croscarmellose sodium NF, type A 0 to 25 Microcrystalline cellulose, NF 0 to 225 Talc USP 0 to 25 to a uniform consistency. ______________________________________

Claim 6

A pharmaceutical ibuprofen dry granulate composition according to claim 4 adapted for making extensive numbers of compressed tablets therefrom, each compressed tablet containing approximately 800 mg. of ibuprofen which comprises (a) a dry granulate composition containing the following ingredients: ______________________________________ Amount to Equal Ingredient Mg./Tablet ______________________________________ Ibuprofen 720 to 880 Croscarmellose sodium NF, Type A 54 to 67 Colloidal silicon dioxide NF 7 to 9 Magnesium stearate 0.5 to 1.5 ______________________________________ which dry granulate compositions (a) is then further mixed to essentially uniform consistency with ______________________________________ Amount to Equal Ingredient Mg./Tablet ______________________________________ Croscarmellose sodium NF, Type A 13 to 17 Microcrystalline cellulose, NF 170 to 210 Colloidal silicon dioxide, NF 13 to 17 and Talc 8 to 12 ______________________________________

Claim 7

A pharmaceutical ibuprofen dry granulate composition according to claim 4 adapted for making extensive numbers of compressed tablets therefrom, each compressed tablet containing approximately 1000 mg. of ibuprofen, which comprises (A) a dry granulate composition containing the following ingredients: ______________________________________ Amount to Equal Ingredient Mg./Tablet ______________________________________ Ibuprofen USP 900 to 1100 mg. Croscarmellose sodium NF, Type A 68 to 84 mg. Colloidal Silicon Dioxide, NF 9 to 11 Magnesium Stearate 0.75 to 1.75 ______________________________________ which dry granulate composition (A) is then further mixed to essentially uniform consistency with ______________________________________ Amount to Equal Ingredient Mg./Tablet ______________________________________ Croscarmellose Sodium NF, Type A 13 to 17 Colloidal Silicon Dioxide NF 3 to 7 and Talc NF 10 to 15 to a uniform consistency. ______________________________________

Claim 8

A pharmaceutical ibuprofen dry granulate composition according to claim 4, adapted for filling into extensive numbers of gelatin capsules, each capsule to contain approximately 200 mg. of ibuprofen which comprises:

Claim 9

(A) a dry granulate composition containing the following ingredients: ______________________________________ Ingredient Amount to Equal Mg./Capsule ______________________________________ Ibuprofen USP 190 to 210 Croscarmellose Sodium NF 13.5 to 16.5 Type A Colloidal Silicon Dioxide, NF 1.5 to 2.5 Magnesium Stearate NF 0.23 to 0.3 (Powder, Food Grade) ______________________________________ which dry granulate composition (A) is then further mixed with the following additional extragranular ingredients: ______________________________________ Ingredient Amount to Equal Mg./Capsule ______________________________________ Magnesium stearate, NF 5 to 7 (powder, food grade) Mineral Oil USP 6 to 8 Microcrystalline cellulose NF 100 to 110 Pregelatinized starch NF 60 to 80 to a uniform consistency. ______________________________________

Claim 10

(A) a dry granulate composition containing the following ingredients: ______________________________________ Ingredient Amount to Equal Mg./Capsule ______________________________________ Ibuprofen USP 190 to 210 Croscarmellose Sodium NF 13.5 to 16.5 Type A Colloidal Silicon Dioxide, NF 1.5 to 2.5 Magnesium Stearate NF 0.23 to 0.3 (Powder, Food Grade) ______________________________________ which dry granulate composition (A) is then further mixed with the following additional extragranular ingredients: ______________________________________ Ingredient Amount to Equal Mg./Capsule ______________________________________ Magnesium stearate, NF 5 to 7 (powder, food grade) Mineral Oil USP 6 to 8 Microcrystalline cellulose NF 100 to 110 Pregelatinized starch NF 60 to 80 to a uniform consistency. ______________________________________

Claim 11

A process for preparing a pharmaceutical ibuprofen granulate composition, which is useful for preparing compressed tablets or filled capsules containing from 100 to 1200 mg. of ibuprofen per dosage unit which comprises: (1) dry mixing a composition containing ibuprofen and croscarmellose sodium NF, Type A or B, in proportions of from about 85 to 99 percent, W/W of ibuprofen based upon the weight of the total mixture, to about 1 to about 15 percent, W/W of croscarmellose sodium NF, based upon the weight of this mixture to essentially uniform consistency, (2) passing the mixture from step (1) through a roller compactor or slugging the composition from step (1), and (3) sizing the resulting compacted or slugged composition from step (2) to form a granulate of essentially uniform size.

Claim 12

A process for preparing a pharmaceutical ibuprofen granulate composition, which is useful for preparing compressed tablets or filled capsules containing from 100 to 1200 mg. of ibuprofen per dosage unit which comprises: (1) dry mixing a composition containing ibuprofen and croscarmellose sodium NF, Type A or B, in proportions of from about 85 to 99 percent, W/W of ibuprofen based upon the weight of the total mixture, to about 1 to about 15 percent, W/W of croscarmellose sodium NF, based upon the weight of this mixture to essentially uniform consistency, (2) passing the mixture from step (1) through a roller compactor or slugging the composition from step (1), and (3) sizing the resulting compacted or slugged composition from step (2) to form a granulate of essentially uniform size.

Claim 13

A process according to claim 8 wherein the composition being dry mixed in step (1) further includes from 0.4 to 1 percent W/W of colloidal silicon dioxide, based on the weight of the total composition being mixed.