Brand new medicinal composition containing levamlodipine and losartan potassium and preparation method thereof

Abstract

The invention relates to a brand new medicinal composition containing levamlodipine and losartan potassium and a preparation method thereof. The composition comprises the levamlodipine and the losartan potassium serving as active ingredients and pharmaceutically acceptable auxiliary materials, wherein the levamlodipine refers to a levamlodipine besylate crystal; and the characteristic peaks of the crystal in an X-ray powder diffraction pattern obtained by measuring through Cu-K alpha rays are displayed when 2 theta is 8.0 degrees, 12.1 degrees, 15.4 degrees, 17.0 degrees, 19.8 degrees, 21.6 degrees, 23.0 degrees, 24.3 degrees, 25.7 degrees, 27.4 degrees, 30.7 degrees and 33.5 degrees. Since the composition contains the crystal which can improve the solubility of levamlodipine besylate, synchronous release of the levamlodipine besylate and the losartan potassium can be realized, and the synergic action of the levamlodipine besylate and the losartan potassium is brought into fuller play. In the method, a direct powder tableting process is adopted; and the method has a simple process, a short production period and low production cost.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to a brand-new pharmaceutical composition containing levamlodipine and losartan potassium and a preparation method thereof. Background technique

[0002] Levoamlodipine besylate is white or off-white powder, its chemical name is (s)-(-)-3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4- (2-Chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulfonate, molecular formula C 20 h 25 N 2 o 5 Cl·C 6 h 6 o 3 S, molecular weight 567.1, structural formula:

[0003]

[0004] Levoamlodipine besylate belongs to the long-acting dihydropyridine (DHP) calcium antagonistic drug, which is separated on the basis of amlodipine, and its drug effect is twice that of racemic amlodipine. Levoamlodipine has the effect of protecting renal function in EH patients, which is not only dependent on the decrease of systemic blood pressure. Also because the drug can permanently ex...

Examples

Embodiment 1

[0080] [embodiment 1] preparation of levamlodipine besylate crystal

[0081] 1) dissolving levamlodipine besylate in a mixed solvent of dichloromethane and ethanol to obtain a dichloromethane / ethanol solution of levamlodipine besylate;

[0082] 2) Add n-heptane dropwise to the dichloromethane / ethanol solution of levamlodipine besylate obtained in step 1) under an ultrasonic field until crystallization occurs;

[0083] 3) Turn off the ultrasonic field, let stand, filter, wash the filter cake with dichloromethane and ethanol respectively, and dry to obtain the levamlodipine besylate crystal.

[0084] Gained levamlodipine besylate crystals use Cu-Kα rays to measure characteristic peaks in the X-ray powder diffraction pattern obtained at 2θ of 8.0°, 12.1°, 15.4°, 17.0°, 19.8°, 21.6°, 23.0° , 24.3°, 25.7°, 27.4°, 30.7° and 33.5° display, such as figure 1 shown.

[0085] Below is embodiment 2-9, and preparation method is with embodiment 1, and its concrete process parameter is sh...

Embodiment 1

[0098] [Preparation Example 1] Levoamlodipine Besylate / Losartan Potassium Tablets

[0099] The prescription is the same as the pharmaceutical composition Example 1, the prescription is to make 1000 tablets, and its preparation method is to further carry out the following steps 4) and step 5) to the standby mixed powder obtained in step 3) to obtain tablets:

[0100] 4) Sampling and testing the mixed powder, calculating the tablet weight according to the content determination results, and performing direct powder compression of the obtained pharmaceutical composition powder;

[0101] 5) Prepare the coating solution, adjust the inlet air temperature to 60°C, preheat the plain tablet temperature to 50°C, adjust the compressed air pressure to 0.35MPa, make the sprayed coating solution into a fine mist, and perform film coating. Coating time was 1.5 hours, and the tablet weight gain was 0.16%. Stop coating, adjust the air inlet temperature to 60° C., and continue drying for 10 minu...

Embodiment 2

[0102] [Preparation Example 2] Levoamlodipine Besylate / Losartan Potassium Tablets

[0103] The prescription is the same as the pharmaceutical composition example 2, and the prescription is to make 1000 tablets, and its preparation method is to further carry out the following steps 4) and step 5) to the standby mixed powder obtained in step 3) to obtain tablets:

[0104] 4) Sampling and testing the mixed powder, calculating the tablet weight according to the content determination results, and performing direct powder compression of the obtained pharmaceutical composition powder;

[0105] 5) Prepare the coating solution, adjust the inlet air temperature to 60°C, preheat the plain tablet temperature to 45°C, adjust the compressed air pressure to 0.25MPa, make the sprayed coating solution into a fine mist, and perform film coating. The coating time was 2 hours, and the tablet weight gain was 0.08%. Stop coating, adjust the air inlet temperature to 60°C, and continue drying for 10 ...

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to a brand-new pharmaceutical composition containing levamlodipine and losartan potassium and a preparation method thereof. Background technique

[0002] Levoamlodipine besylate is white or off-white powder, its chemical name is (s)-(-)-3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4- (2-Chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulfonate, molecular formula C 20 h 25 N 2 o 5 Cl·C 6 h 6 o 3 S, molecular weight 567.1, structural formula:

[0003]

[0004] Levoamlodipine besylate belongs to the long-acting dihydropyridine (DHP) calcium antagonistic drug, which is separated on the basis of amlodipine, and its drug effect is twice that of racemic amlodipine. Levoamlodipine has the effect of protecting renal function in EH patients, which is not only dependent on the decrease of systemic blood pressure. Also because the drug can permanently ex...

Examples

Embodiment 1

[0080] [embodiment 1] preparation of levamlodipine besylate crystal

[0081] 1) dissolving levamlodipine besylate in a mixed solvent of dichloromethane and ethanol to obtain a dichloromethane / ethanol solution of levamlodipine besylate;

[0082] 2) Add n-heptane dropwise to the dichloromethane / ethanol solution of levamlodipine besylate obtained in step 1) under an ultrasonic field until crystallization occurs;

[0083] 3) Turn off the ultrasonic field, let stand, filter, wash the filter cake with dichloromethane and ethanol respectively, and dry to obtain the levamlodipine besylate crystal.

[0084] Gained levamlodipine besylate crystals use Cu-Kα rays to measure characteristic peaks in the X-ray powder diffraction pattern obtained at 2θ of 8.0°, 12.1°, 15.4°, 17.0°, 19.8°, 21.6°, 23.0° , 24.3°, 25.7°, 27.4°, 30.7° and 33.5° display, such as figure 1 shown.

[0085] Below is embodiment 2-9, and preparation method is with embodiment 1, and its concrete process parameter is sh...

Embodiment 1

[0098] [Preparation Example 1] Levoamlodipine Besylate / Losartan Potassium Tablets

[0099] The prescription is the same as the pharmaceutical composition Example 1, the prescription is to make 1000 tablets, and its preparation method is to further carry out the following steps 4) and step 5) to the standby mixed powder obtained in step 3) to obtain tablets:

[0100] 4) Sampling and testing the mixed powder, calculating the tablet weight according to the content determination results, and performing direct powder compression of the obtained pharmaceutical composition powder;

[0101] 5) Prepare the coating solution, adjust the inlet air temperature to 60°C, preheat the plain tablet temperature to 50°C, adjust the compressed air pressure to 0.35MPa, make the sprayed coating solution into a fine mist, and perform film coating. Coating time was 1.5 hours, and the tablet weight gain was 0.16%. Stop coating, adjust the air inlet temperature to 60° C., and continue drying for 10 minu...

Embodiment 2

[0102] [Preparation Example 2] Levoamlodipine Besylate / Losartan Potassium Tablets

[0103] The prescription is the same as the pharmaceutical composition example 2, and the prescription is to make 1000 tablets, and its preparation method is to further carry out the following steps 4) and step 5) to the standby mixed powder obtained in step 3) to obtain tablets:

[0104] 4) Sampling and testing the mixed powder, calculating the tablet weight according to the content determination results, and performing direct powder compression of the obtained pharmaceutical composition powder;

[0105] 5) Prepare the coating solution, adjust the inlet air temperature to 60°C, preheat the plain tablet temperature to 45°C, adjust the compressed air pressure to 0.25MPa, make the sprayed coating solution into a fine mist, and perform film coating. The coating time was 2 hours, and the tablet weight gain was 0.08%. Stop coating, adjust the air inlet temperature to 60°C, and continue drying for 10 ...

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