Solid pharmaceutical composition comprising amlodipine and losartan and process for producing same
View Patent ↗The present invention relates to a solid pharmaceutical composition for preventing or treating cardiovascular disorders comprising amlodipine or a pharmaceutically acceptable salt thereof and losartan or a pharmaceutically acceptable salt thereof, which exhibits high dissolution rates of amlodipine and losartan even under a low pH condition and improved storage stability.
1. A solid pharmaceutical composition comprising amlodipine or a pharmaceutically acceptable salt thereof and losartan or a pharmaceutically acceptable salt thereof,
wherein amlodipine or a pharmaceutically acceptable salt thereof is of granular form, and losartan or a pharmaceutically acceptable salt thereof is of granule form, wherein the granule of amlodipine or a pharmaceutically acceptable salt thereof and the granule of losartan or a pharmaceutically acceptable salt thereof are separated from each other;
wherein the composition comprises losartan or a pharmaceutically acceptable salt thereof in an amount ranging from 5 to 22.3% by weight based on the total weight of the composition;
wherein the composition comprises a granule form of losartan of which the percentage of a fine granule passing through a 75 μm mesh is below 50%;
wherein the dissolution rate of amlodipine in the solid pharmaceutical composition is 80% or more thereof in 30 minutes at a pH range of 1.0 to 2.0; and
wherein the dissolution rate of losartan in the solid pharmaceutical composition is 80% or more thereof in 30 minutes at a pH range of 1.0 to 2.0.
2. The composition of claim 1 , which comprises a granule form of losartan of which the percentage of a fine granule passing through a 75 μm mesh is below 25%.
3. The composition of claim 2 , which comprises a granule form of losartan of which the percentage of a fine granule passing through a 75 μm mesh is below 10%.
4. The composition of claim 1 , wherein the pharmaceutically acceptable salt of amlodipine is amlodipine camsylate.
5. A method for preparing the solid composition of claim 1 comprising amlodipine in a granule form and losartan in a granule form, said amlodipine granules and losartan granules being separated from each other, which comprises the steps of:
a) granulating and drying a mixture of losartan or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient to obtain losartan granules;
b) granulating and drying a mixture of amlodipine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient to obtain amlodipine granules; and
c) mixing the losartan granules obtained in step a) with the amlodipine granules obtained in step b) to give the composition,
wherein the solid composition comprises losartan or a pharmaceutically acceptable salt thereof in an amount ranging from 5 to 22.3% by weight based on the total weight of the composition;
wherein the composition comprises a granule form of losartan of which the percentage of a fine granule passing through a 75 μm mesh is below 50%;
wherein the dissolution rate of amlodipine in the solid pharmaceutical composition is 80% or more thereof in 30 minutes at a pH range of 1.0 to 2.0; and
wherein the dissolution rate of losartan in the solid pharmaceutical composition is 80% or more thereof in 30 minutes at a pH range of 1.0 to 2.0.