CN115869272A - Amlodipine besylate tablet and preparation method thereof - Google Patents
Amlodipine besylate tablet and preparation method thereof Download PDFInfo
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- CN115869272A CN115869272A CN202111154374.5A CN202111154374A CN115869272A CN 115869272 A CN115869272 A CN 115869272A CN 202111154374 A CN202111154374 A CN 202111154374A CN 115869272 A CN115869272 A CN 115869272A
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- calcium carbonate
- amlodipine besylate
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- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 229960004005 amlodipine besylate Drugs 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 40
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 35
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 31
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 31
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 31
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 31
- 229920000881 Modified starch Polymers 0.000 claims abstract description 27
- 229920002472 Starch Polymers 0.000 claims abstract description 20
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 20
- 239000008107 starch Substances 0.000 claims abstract description 20
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 12
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 12
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 12
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims description 35
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 18
- 239000011575 calcium Substances 0.000 claims description 18
- 229910052791 calcium Inorganic materials 0.000 claims description 18
- 238000007873 sieving Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 11
- 238000010008 shearing Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000008119 colloidal silica Substances 0.000 claims description 5
- 239000007779 soft material Substances 0.000 claims description 5
- 239000002131 composite material Substances 0.000 claims description 4
- 238000005550 wet granulation Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 abstract description 25
- 235000019698 starch Nutrition 0.000 abstract description 7
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 3
- 229940057948 magnesium stearate Drugs 0.000 abstract 1
- 239000000463 material Substances 0.000 description 16
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 10
- 229960000528 amlodipine Drugs 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000002609 medium Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000008186 active pharmaceutical agent Substances 0.000 description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 4
- 235000019700 dicalcium phosphate Nutrition 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical group [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an amlodipine besylate tablet and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The amlodipine besylate tablet comprises amlodipine besylate, a calcium carbonate starch compound, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, colloidal silicon dioxide and pregelatinized starch, wherein the calcium carbonate starch compound is prepared from calcium carbonate and the pregelatinized starch in a certain mass ratio. The amlodipine besylate tablet prepared by the invention has the advantages of stable dissolution, simple and convenient operation, regular tablet surface, small dissolution change during the stability period and the like.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to an amlodipine besylate tablet and a preparation method thereof.
Background
The amlodipine besylate tablet is a calcium ion antagonist, and can selectively inhibit calcium ions from entering smooth muscle cells and myocardial cells through a membrane to play a role, so that the tablet can directly act on vascular smooth muscle, reduce peripheral vascular resistance and further reduce blood pressure.
Amlodipine is unstable to light, moisture, heat and acid, and the existing preparation method generally needs high-temperature and high-humidity conditions, thereby having serious influence on the stability of the product. The amlodipine tablet contains auxiliary materials such as anhydrous calcium hydrophosphate and microcrystalline cellulose, and the density difference between different auxiliary materials is large, so that the problem of uneven content is easy to occur in the premixing or total mixing process, and the product quality is further influenced. Amlodipine besylate, which is degraded in an acidic medium. The pH value of the amlodipine besylate composition is about 7, the pH value of the amlodipine free base composition is about 9, and the auxiliary material preparation with weakly alkaline pH value is more suitable for the development of the preparation product. Calcium carbonate has higher alkalinity than calcium hydrogen phosphate, and is more suitable for tablet adjuvants.
The amlodipine besylate tablet uses anhydrous calcium hydrophosphate in the original prescription composition, and has the problems of incomplete dissolution and reduced dissolution during the stability period. Compared with calcium carbonate, the anhydrous calcium hydrogen phosphate auxiliary material has better compressibility and fluidity, but the deformation mechanism of the anhydrous calcium hydrogen phosphate is brittle fracture in the tabletting process, and particularly, under the condition of large prescription amount, the tablets have the problems of fault and top crack, so that the surface of the tablets is regular.
Disclosure of Invention
The invention aims to overcome the defects and shortcomings and provides an amlodipine besylate tablet and a preparation method thereof.
In order to realize the purpose, the technical scheme adopted by the invention is as follows:
the amlodipine besylate tablet is characterized by comprising the following components in percentage by weight:
the calcium carbonate-starch composite is obtained by mixing calcium carbonate and pregelatinized starch in a certain mass ratio, and is characterized in that the mass ratio of the calcium carbonate to the pregelatinized starch is 8-10.
The amlodipine besylate tablet and the preparation method are characterized by comprising the following steps:
(1) Adding calcium carbonate and pregelatinized starch into a wet granulator according to a certain mass ratio, premixing, adding water to prepare a soft material, sieving with a 40-mesh sieve, carrying out wet granulation, and drying to prepare a calcium carbonate-starch compound;
(2) Respectively sieving the pretreated amlodipine besylate, the calcium carbonate-starch compound and the microcrystalline cellulose with a 60-mesh sieve; sieving colloidal silicon dioxide and pregelatinized starch with 50 mesh sieve;
(3) Mixing the amlodipine besylate obtained in the step (2) with 1/2 of the amount of the microcrystalline cellulose according to the prescription to prepare a premix (1);
(4) Mixing the colloidal silicon dioxide and the pregelatinized starch obtained in the step (2) with a premix (1), croscarmellose sodium and 1/2 of the prescribed amount of calcium carbonate-starch compound for 2min to prepare a premix (2);
(5) Putting the rest 1/2 of the prescription amount of microcrystalline cellulose and 1/2 of the prescription amount of calcium carbonate starch compound into a wet granulator for rinsing, adding the premix (2), mixing for 5min, stirring at 3rpm, and shearing at 10rpm;
(6) Adding the magnesium stearate with the prescription amount into the step (5), and mixing for 5min;
(7) Tabletting by adopting a punch with the length of 11.5mm and the length of 6.1mm, wherein the theoretical weight of the tablet is 250mg, and the hardness is controlled to be 17-20kg.
The amlodipine besylate tablet and the preparation method are characterized in that the D90 of the pretreated amlodipine besylate is between 20 and 40 mu m; the D90 of the microcrystalline cellulose is between 120 and 160 mu m; magnesium stearate D90 is less than 200 μm.
The amlodipine besylate tablet and the preparation method are characterized in that the premixing time of calcium carbonate and pregelatinized starch is 3-5 minutes, and the soft material preparation time is 1-2 minutes; amlodipine besylate is mixed with 1/2 of the prescribed amount of microcrystalline cellulose for 1-2 minutes.
Advantageous effects
1. The amlodipine besylate tablet prepared by the invention has good dissolution fitting with the original ground reference preparation, simple preparation process, conventional operation, suitability for industrialized batch production, good process reproducibility and accordance with the quality standard of medicines.
2. According to the invention, calcium carbonate and pregelatinized starch are mixed in a specific ratio and subjected to wet granulation, so that the prepared tablet has good appearance, excellent content and dissolution quality attribute, no obvious change in dissolution during stability, and the overall quality level of the amlodipine tablet is improved.
Drawings
FIG. 1 is the dissolution curve of amlodipine besylate tablet under pH6.8 medium.
Detailed Description
For the purpose of illustration and for the purpose of promoting an understanding of the invention, the following examples are set forth to further illustrate the claimed embodiments, but it is to be understood that the scope of the invention is not limited to the following examples.
Example 1: using the invention
The prescription composition is as follows:
| mg/tablet | Is in percentage by weight | g/1000 tablets | |
| Amlodipine besylate | 6.935 | 2.77 | 6.935 |
| Calcium |
100 | 40 | 100 |
| Microcrystalline cellulose | 93.33 | 37.33 | 93.33 |
| Croscarmellose sodium | 7.5 | 3 | 7.5 |
| Magnesium stearate | 1.25 | 0.5 | 1.25 |
| Colloidal silica | 1 | 0.4 | 1 |
| Pregelatinized |
40 | 16 | 40 |
The preparation process comprises the following steps:
1) Adding calcium carbonate and pregelatinized starch into a wet granulator according to the mass ratio of 9:1, premixing for 5 minutes, adding adhesive water to prepare a soft material for 1 minute, sieving with a 40-mesh sieve, performing wet granulation, and performing drying treatment to prepare the calcium carbonate-starch composite.
2) Material pretreatment: crushing the amlodipine bulk drug to D90 of about 30 mu m, and sieving a calcium carbonate-starch compound and a microcrystalline cellulose auxiliary material with a 60-mesh sieve for dispersion;
3) Mixing amlodipine besylate API with half of microcrystalline cellulose for 1min to prepare a premix (1);
4) Mixing colloidal silicon dioxide and pregelatinized starch, sieving with 50 mesh sieve, and mixing with premix (1), croscarmellose sodium and half of calcium carbonate starch compound for 2min; preparing a premix (2);
5) And (3) putting the rest microcrystalline cellulose and calcium carbonate starch compound into a wet granulator for rinsing, adding the premix (2), mixing for 5min, stirring at 3rpm, and shearing at 10rpm.
6) Mixing: weighing magnesium stearate in a prescription amount, and mixing the magnesium stearate with the premixed material for 5min;
7) Tabletting: tabletting by using a punch with the length of 11.5mm and the length of 6.1mm, wherein the theoretical weight of the tablet is 250mg, and the hardness is controlled to be 17-20kg.
Example 2: anhydrous calcium hydrophosphate as calcium carbonate-starch substitute compound
The prescription composition is as follows:
| mg/tablet | Is in percentage by weight | g/2000 tablets | |
| Amlodipine besylate | 6.935 | 2.77 | 13.87 |
| Anhydrous |
100 | 40 | 200 |
| Microcrystalline cellulose | 93.33 | 37.33 | 186.66 |
| Croscarmellose sodium | 7.5 | 3 | 15 |
| Magnesium stearate | 1.25 | 0.5 | 2.5 |
| Colloidal silica | 1 | 0.4 | 2 |
| Pregelatinized |
40 | 16 | 80 |
The preparation process comprises the following steps:
1) Material pretreatment: crushing the amlodipine bulk drug to D90 of about 30 mu m, and sieving anhydrous calcium hydrophosphate and microcrystalline cellulose auxiliary materials by a 60-mesh sieve for dispersion;
2) Mixing amlodipine besylate API with anhydrous calcium hydrophosphate and microcrystalline cellulose with a half of the prescription amount for 1min to prepare premix (1);
3) Mixing colloidal silicon dioxide and pregelatinized starch, sieving with 50 mesh sieve, mixing with premix (1) and croscarmellose sodium for 2min to obtain premix (2);
4) Adding the rest microcrystalline cellulose into premix (2), mixing for 5min, stirring at 3rpm, and shearing at 10rpm.
5) Mixing: weighing magnesium stearate in a prescription amount, and mixing the magnesium stearate with the premixed material for 5min;
6) Tabletting: tabletting by using a punch with the length of 11.5mm and the length of 6.1mm, wherein the theoretical weight of the tablet is 250mg, and the hardness is controlled to be 17-20kg.
Example 3: balancing the formula with microcrystalline cellulose such that the pregelatinized starch: microcrystalline cellulose =1:1 (comparison case)
The prescription composition is as follows:
| mg/tablet | Is in percentage by weight | g/2000 tablets | |
| Amlodipine besylate | 6.935 | 2.77 | 13.85 |
| Microcrystalline cellulose | 116.66 | 46.67 | 233.32 |
| Croscarmellose sodium | 7.5 | 3 | 15 |
| Magnesium stearate | 1.25 | 0.5 | 2.5 |
| Colloidal silica | 1 | 0.4 | 2 |
| Pregelatinized starch | 116.66 | 46.67 | 233.32 |
The preparation process comprises the following steps:
1) Material pretreatment: crushing the amlodipine bulk drug to D90 of about 30 mu m, and sieving the microcrystalline cellulose auxiliary material with a 60-mesh sieve;
2) Mixing amlodipine besylate API with microcrystalline cellulose of which the amount is indicated by the formula to be half for 1min to prepare a premix (1);
3) Mixing colloidal silicon dioxide and pregelatinized starch, sieving with 50 mesh sieve, mixing with premix (1) and croscarmellose sodium for 2min to obtain premix (2);
4) Adding the rest microcrystalline cellulose into premix (2), mixing for 5min, stirring at 3rpm, and shearing at 10rpm.
5) Mixing: weighing magnesium stearate in a prescription amount, and mixing the magnesium stearate with the premixed material for 5min;
6) Tabletting: tabletting by using a punch with the length of 11.5mm and the length of 6.1mm, wherein the theoretical weight of the tablet is 250mg, and the hardness is controlled to be 17-20kg.
Example 4: pregelatinized starch instead of calcium carbonate starch complex (comparative case)
The prescription composition is as follows:
| mg/tablet | Is in percentage by weight | g/2000 tablets | |
| Amlodipine besylate | 6.935 | 2.77 | 13.85 |
| Microcrystalline cellulose | 93.33 | 37.33 | 186.67 |
| Croscarmellose sodium | 7.5 | 3 | 15 |
| Magnesium stearate | 1.25 | 0.5 | 2.5 |
| Colloidal silica | 1 | 0.4 | 2 |
| Pregelatinized starch | 140 | 56 | 280 |
| Total up to | 250 | 100 | 500 |
The preparation process comprises the following steps:
1) Material pretreatment: crushing the amlodipine bulk drug to D90 of about 30 mu m, and sieving the microcrystalline cellulose auxiliary material with a 60-mesh sieve;
2) Mixing amlodipine besylate API with microcrystalline cellulose of which the amount is indicated by the prescription for 1min to prepare premix (1);
3) Mixing colloidal silicon dioxide and pregelatinized starch, sieving with 50 mesh sieve, mixing with premix (1) and croscarmellose sodium for 2min to obtain premix (2);
4) Adding the rest microcrystalline cellulose into premix (2), mixing for 5min, stirring at 3rpm, and shearing at 10rpm.
5) Mixing: weighing magnesium stearate in a prescription amount, and mixing the magnesium stearate with the premixed material for 5min;
6) Tabletting: tabletting by using a punch with the length of 11.5mm and the length of 6.1mm, wherein the theoretical weight of the tablet is 250mg, and the hardness is controlled to be 17-20kg.
Dissolution test:
the determination method comprises the following steps: samples in each example were selected for evaluation of the fit to the dissolution curve of the self-preparation at 37 ℃ and pH6.8 paddle (50 rpm for the sedimentation basket), 0.01M hydrochloric acid + EDTA (75 rpm), pH4.5 paddle (50 rpm), aqueous media paddle (50 rpm), 900 mL. And sampling at corresponding time points, detecting and calculating the elution amount of each tablet. The examination results are shown in the table. The dissolution test method refers to the dissolution and release determination method of the 2020 edition Chinese pharmacopoeia 0931 to calculate the cumulative dissolution, and the dissolution results show that in each implementation case, except for the medium of the pH6.8 paddle method (50 rpm of the settling basket), the other implementation cases are all rapidly dissolved in each medium (more than 85% in 15 minutes), so the dissolution data of the key medium of the pH6.8 paddle method (50 rpm of the settling basket) are explained and presented in detail.
TABLE 1 dissolution Profile of amlodipine tablets in pH6.8 paddle method (sediment basket 50 rpm)
| Time (min) | Example 1 | Example 2 | Example 3 | Example 4 | Reference formulation |
| 5 | 52 | 65 | 82 | 76 | 55 |
| 10 | 67 | 68 | 89 | 86 | 69 |
| 15 | 71 | 70 | 90 | 88 | 73 |
| 20 | 75 | 73 | 91 | 88 | 75 |
| 30 | 79 | 73 | 90 | 89 | 79 |
| 45 | 81 | 75 | 92 | 89 | 84 |
| 60 | 83 | 77 | 92 | 88 | 87 |
| 90 | 85 | 77 | 92 | 90 | 92 |
| 120 | 89 | 81 | 93 | 89 | 96 |
| 180 | 90 | 83 | 93 | 91 | 98 |
| f2 | 72 | 50 | 39 | 43 |
The test result shows that the dissolution of the examples 1 and 2 can be consistent with the dissolution of the original preparation in a dissolution medium with pH6.8 paddle method (50 rpm of a settling basket); but example 1 is much more similar to the reference than example 2. Examples 3, 4 do not correspond to the dissolution behavior of the reference formulation.
Dissolution change test during stability:
taking the samples of the examples 1 and 2 of the invention and the reference preparation sample, carrying out accelerated stability investigation according to the pharmaceutical preparation stability test guiding principle in the 2020 edition of Chinese pharmacopoeia under the conditions of 40 ℃ plus or minus 2 ℃ and RH75 percent plus or minus 5 percent, sampling at 0 month, 1 month, 2 months, 3 months and 6 months after standing, and investigating the dissolution change condition in the stability period, wherein the results are shown in Table 2.
Table 2 dissolution of amlodipine tablets during stability in pH6.8 medium
Test results show that the dissolution change condition of the sample prepared by the invention during the stability period is good and basically consistent with the dissolution change condition of the original preparation sample during the stability period; in example 2, a significant decrease or slowing of dissolution occurred during the stabilization period. Since the dissolution results of examples 3 and 4 were not satisfactory, the change in dissolution during the stability period was not examined.
Claims (4)
1. The amlodipine besylate tablet is characterized by comprising the following components in percentage by weight:
amlodipine besylate 2 to 3wt%
30 to 50wt% of calcium carbonate-starch composite
30 to 50wt% of microcrystalline cellulose
1 to 5wt% of croscarmellose sodium
Magnesium stearate 0.5-2wt%
0.2 to 0.6wt% of colloidal silica
10 to 20wt% of pregelatinized starch
The calcium carbonate-starch composite is prepared from calcium carbonate and pregelatinized starch in a certain mass ratio, and is characterized in that the mass ratio of the calcium carbonate to the pregelatinized starch is 8-10.
2. The amlodipine besylate tablet and the preparation method according to claim 1, wherein the preparation method comprises the following steps:
(1) Adding calcium carbonate and pregelatinized starch into a wet granulator according to a certain mass ratio, premixing, adding water to prepare a soft material, sieving with a 40-mesh sieve, carrying out wet granulation, and drying to prepare a calcium carbonate-starch compound;
(2) Respectively sieving the pretreated amlodipine besylate, the calcium carbonate-starch compound and the microcrystalline cellulose with a 60-mesh sieve; sieving colloidal silicon dioxide and pregelatinized starch with 50 mesh sieve;
(3) Mixing the amlodipine besylate obtained in the step (2) with 1/2 of the prescription amount of microcrystalline cellulose to prepare premix (1)
(4) Mixing the colloidal silicon dioxide and the pregelatinized starch obtained in the step (2) with a premix (1), croscarmellose sodium and 1/2 of the prescribed amount of calcium carbonate-starch compound for 2min to prepare a premix (2);
(5) Putting the rest 1/2 of the prescription amount of microcrystalline cellulose and 1/2 of the prescription amount of calcium carbonate-starch compound into a wet granulator for rinsing, adding the premix (2), mixing for 5min, stirring at 3rpm, and shearing at 10rpm;
adding the magnesium stearate with the prescription amount into the step (5), and mixing for 5min;
and (3) tabletting by using a punch with the length of 11.5mm and the length of 6.1mm, wherein the theoretical weight of the tablet is 250mg, and the hardness is controlled to be 17-20kg.
3. The preparation method according to claim 2, wherein the pretreated amlodipine besylate D90 is between 20 and 40 μm; the microcrystalline cellulose D90 is between 120 and 160 mu m; magnesium stearate D90 is less than 200 μm.
4. The method of claim 2, wherein the pre-mixing time of the calcium carbonate and the pregelatinized starch is 3~5 minutes, and the soft material making time is 1~2 minutes; amlodipine besylate was mixed with the prescribed amount of microcrystalline cellulose 1/2 for a time of 1~2 minutes.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104055742A (en) * | 2014-02-13 | 2014-09-24 | 合肥九研医药科技开发有限公司 | Levamlodipine besylate pharmaceutical composition and preparation method thereof |
| WO2015051771A1 (en) * | 2013-10-08 | 2015-04-16 | Zentiva, K.S. | A stable pharmaceutical composition containing amlodipine and valsartan |
| CN104739799A (en) * | 2013-12-27 | 2015-07-01 | 辰欣药业股份有限公司 | An amlodipine besylate composition used for direct tabletting and a preparing method of tablets of the composition |
| CN109953958A (en) * | 2017-12-25 | 2019-07-02 | 湖南千金协力药业有限公司 | A kind of mixing amlodipine besylate tablets and preparation method thereof |
-
2021
- 2021-09-29 CN CN202111154374.5A patent/CN115869272A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015051771A1 (en) * | 2013-10-08 | 2015-04-16 | Zentiva, K.S. | A stable pharmaceutical composition containing amlodipine and valsartan |
| CN104739799A (en) * | 2013-12-27 | 2015-07-01 | 辰欣药业股份有限公司 | An amlodipine besylate composition used for direct tabletting and a preparing method of tablets of the composition |
| CN104055742A (en) * | 2014-02-13 | 2014-09-24 | 合肥九研医药科技开发有限公司 | Levamlodipine besylate pharmaceutical composition and preparation method thereof |
| CN109953958A (en) * | 2017-12-25 | 2019-07-02 | 湖南千金协力药业有限公司 | A kind of mixing amlodipine besylate tablets and preparation method thereof |
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