Pharmaceutical compositions of amlodipine and atorvastatin

A method for preparing a pharmaceutical composition comprising:

• [A] An atorvastatin granulation comprising:
• Step (1)—dissolving a surface active agent in water and adding and hydrating a binder;
• Step (2)—mixing atorvastatin calcium, an alkalizing agent that forms a pH greater than 5, a filler/diluent, a filler/diluent/disintegrating agent, and a disintegrating agent in a granulating apparatus;
• Step (3)—granulating the powder mix from Step (2) with the solution from Step (1) in the granulating apparatus;
• and
• Step (4)—drying the granulation in a drying apparatus.
• [B] A final formulation comprising:
• Step (1)—adding amlodipine besylate, a filler/diluent, a disintegrating agent, and a glidant to the atorvastatin granulation;
• Step (2)—passing the powder mixture through a mill;
• and
• Step (3)—blending the milled powder mixture and a lubricating agent in a blender to afford a uniformly blended pharmaceutical composition for a solid dosage form.

A pharmaceutical composition comprising amlodipine or pharmaceutically acceptable salts thereof and atorvastatin or pharmaceutically acceptable salts thereof and a carrier containing not more than 0.5% of a compound selected from the group consisting of:

• 5-(4-Fluorophenyl)-2,3-dihydro-β,δ-dihydroxy-3-(1-methylethyl)-2-oxo-4-phenyl-3-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid;
• (2R-trans)-5-(4-Fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3 -carboxamide;
• and
• 3-[(4-Fluorophenyl)carbonyl]-2-(2-methyl-1-oxopropyl)-N,3-diphenyl-2-oxiranecarboxamide;
• after storage at 25° C./60% relative humidity for 24 months.

A pharmaceutical composition comprising amlodipine or pharmaceutically acceptable salts thereof and atorvastatin or pharmaceutically acceptable salts thereof and a carrier containing not more than 1.0% of a compound selected from the group consisting of:

• 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester;
• and
• 6-(2-Chloro-phenyl)-8-methyl-3,4,6,7-tetrahydro-2H- 1,4-benzoxazine-5,7-dicarboxylic acid 5-ethyl ester 7-methyl ester;
• after storage at 25° C./60% relative humidity for 24 months.

A kit for achieving a therapeutic effect in a mammal comprising a therapeutically effective amount of amlodipine or pharmaceutically acceptable salts thereof and a therapeutically effective amount of atorvastatin or pharmaceutically acceptable salts thereof and a carrier in unit dosage form and a container for containing said dosage form containing not more than 0.5% of a compound selected from the group consisting of:

• 5-(4-Fluorophenyl)-2,3 -dihydro-β,δ-dihydroxy-3-(1-methylethyl)-2-oxo-4-phenyl-3-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid;
• (2R-trans)-5 -(4-Fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide;
• and
• 3-[(4-Fluorophenyl)carbonyl]-2-(2-methyl-1-oxopropyl)-N,3-diphenyl-2-oxiranecarboxamide;
• after storage at 25° C./60% relative humidity for 24 months.

A kit for achieving a therapeutic effect in a-mammal comprising a therapeutically effective amount of amlodipine or pharmaceutically acceptable salts thereof and a therapeutically effective amount of atorvastatin or pharmaceutically acceptable salts thereof and a carrier in unit dosage form and a container for containing said dosage form containing not more than 1.0% of a compound selected from the group consisting of:

• 2-(2-Amino-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester;
• and
• 6-(2-Chloro-phenyl)-8-methyl-3,4,6,7-tetrahydro-2H- 1,4-benzoxazine-5,7-dicarboxylic acid 5-ethyl ester 7-methyl ester;
• after storage at 25° C./60% relative humidity for 24 months.