CN105030726A - Method for preparing isradipine capsule - Google Patents
Method for preparing isradipine capsule Download PDFInfo
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- CN105030726A CN105030726A CN201510539483.7A CN201510539483A CN105030726A CN 105030726 A CN105030726 A CN 105030726A CN 201510539483 A CN201510539483 A CN 201510539483A CN 105030726 A CN105030726 A CN 105030726A
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- CN
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- Prior art keywords
- isradipine
- capsule
- preparation
- recipe quantity
- microcrystalline cellulose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 229960004427 isradipine Drugs 0.000 title claims abstract description 41
- 239000002775 capsule Substances 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title abstract description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000008187 granular material Substances 0.000 claims abstract description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 18
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 11
- 229920000881 Modified starch Polymers 0.000 claims abstract description 11
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 11
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 11
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 11
- 239000002245 particle Substances 0.000 claims abstract description 10
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 230000001105 regulatory effect Effects 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 12
- 229920003081 Povidone K 30 Polymers 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 4
- 238000005243 fluidization Methods 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 230000002572 peristaltic effect Effects 0.000 claims description 3
- 238000005453 pelletization Methods 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 abstract description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 abstract description 3
- 229940069328 povidone Drugs 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 2
- 239000007962 solid dispersion Substances 0.000 abstract description 2
- 239000010419 fine particle Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000001694 spray drying Methods 0.000 abstract 1
- 238000005507 spraying Methods 0.000 abstract 1
- 238000005259 measurement Methods 0.000 description 4
- 102220042174 rs141655687 Human genes 0.000 description 4
- 102220043159 rs587780996 Human genes 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010051467 Nephrectasia Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000000489 anti-atherogenic effect Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000003684 cardiac depression Effects 0.000 description 1
- 208000012549 congenital acardia Diseases 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940127292 dihydropyridine calcium channel blocker Drugs 0.000 description 1
- 239000002866 dihydropyridine calcium channel blocker Substances 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 230000001196 vasorelaxation Effects 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for preparing an isradipine capsule. The method comprises the following steps: dissolving an isradipine raw material according to the amount of a prescription in prescribed ethanol, and adding povidone K3 to stir and dissolve; putting prescribed pregelatinized starch and microcrystalline cellulose in a fluidized bed, starting a fan, regulating the air volume to excellent fluidizing, setting the air inlet temperature to be 35-40 DEG C, spraying the solution prepared in the step A when the material temperature rises to 25 DEG C to granulate; and finishing the prepared particles through a 30-mesh screen, adding magnesium stearate, uniformly mixing, and filling capsules with the particles. According to the method, the raw materials and the auxiliaries are used for preparing solid dispersion by adopting a spray drying mode, are prepared to form fine particles by one step, and are used for filling capsules, so that the dissolution in vitro of the capsule can be effectively increased, the production cost can be reduced, the bioavailability of the capsule can be improved, and a better clinical curative effect can be achieved.
Description
Technical field
The invention belongs to technical field of pharmaceutical chemistry, relate to a kind of preparation method of isradipine capsule.
Background technology
Isradipine is dihydropyridine calcium channel blocker, by retardance cross-film flow of calcium ions, and the contraction that causes of Selective depression depolarization effectively, and play a role on cardiac muscle and vascular smooth muscle.This product has stronger vasorelaxation action, and acardia inhibitory action, cause reflex tachycardia hardly.Clinical and zoopery proves; this medical instrument has obvious hypotensive effect and study of anti-atherogenic effect; by maintaining or recovering the SE blood flow of left ventricle; prevent ischemic injuries; improve the quantity of motion of angina pectoris and congestive heart failure patients; treating hypertensive while, there is protective effect to heart.Isradipine can increase the excretion of sodium ion and water, has diuresis, and energy nephrectasia efferent artery, reduces capillary of kidney pressure, have protective effect to kidney.
Isradipine is a kind of effective calcium channel blocker, there is the effect of blood vessel dilating, minimizing peripheral vascular resistance, increase arteria coronaria and brain vessel blood significantly, very little to Cardiac depression effect especially, prolonged application well-tolerated, one of critical treatment medicine becoming the diseases such as hypertension.
Raw material isradipine is not soluble drug in water, existing capsule preparation method thereof be by after isradipine raw material micronization processes again with adjuvant mixing granulation, filled capsules after dry.Capsule dissolubility prepared by existing preparation method is low, and the production cycle is long, and cost is higher.
Summary of the invention
The object of the invention is to for the deficiencies in the prior art, a kind of preparation method of isradipine capsule is provided.
For achieving the above object, the technical solution adopted for the present invention to solve the technical problems is:
A preparation method for isradipine capsule, comprises the steps:
A, get recipe quantity isradipine raw material and be dissolved in recipe quantity ethanol, then add PVP K30 stirring and dissolving;
B, get recipe quantity pregelatinized Starch and microcrystalline Cellulose is put in fluid bed, start blower fan, regulating air volume is good to fluidisation, and arranging inlet temperature is 35 ~ 40 DEG C, when temperature of charge rises to 25 DEG C, sprays into solution prepared by steps A and granulates;
C, obtained granule is crossed 30 mesh sieve granulate, add magnesium stearate, mix homogeneously, particles filled capsule after mixing.
As preferably, described isradipine capsule comprises the component of following parts by weight:
Isradipine 2.5-5.0 part
Pregelatinized Starch 35-65 part
Microcrystalline Cellulose 15-25 part
PVP K30 8-12 part
Magnesium stearate 0.5-1.5 part
Ethanol 60-70 part
Make: 1000 capsules.
As optimal way, in described step B, in pelletization, control atomizing pressure 0.2 ~ 0.5mpa and peristaltic pump rotating speed 10 ~ 15r/min.
As optimal way, in described step B, continue after having granulated to be dried to moisture≤2%.
The present invention adopts spray-dired mode to be prepared into solid dispersion by raw materials used together with adjuvant, a step makes fine grained simultaneously, and then filled capsules, effectively can increase the dissolution in vitro of this product and reduce production cost, improve the bioavailability of this medicine simultaneously, reach better clinical efficacy.
Detailed description of the invention
All features disclosed in this description, or the step in disclosed all methods or process, except mutually exclusive feature and/or step, all can combine by any way.
Comparative example 1: isradipine raw material different-grain diameter is on the impact of stripping
Get isradipine raw material, adopt different processing modes (to cross 100 mesh sieves; Pulverized 200 mesh sieves, super micron mill micropowder) prepare different particle diameters, add pregelatinized Starch and mix homogeneously with microcrystalline Cellulose, add 3% povidone solution and granulate, difference filled capsules after dry granulate, with intelligent dissolution determination dissolution.Result is as follows:
Table 1 isradipine different-grain diameter stripping curve measurement result
| Processing mode | Particle diameter (μm) | 15min | 30min | 45min | 60min |
| Cross 100 orders | D50＝90.5，D90＝157.3 | 32.8 | 47.3 | 53.4 | 58.7 |
| Pulverized 200 orders | D50＝38.7，D90＝70.5 | 37.9 | 48.8 | 55.2 | 60.8 |
| Micronizing | D50＝14.5，D90＝30.7 | 45.2 | 52.4 | 60.3 | 65.7 |
Comparative example 2: the different prescription of isradipine capsule is on the impact of dissolution
Get isradipine raw material, after adopting super micron mill to pulverize (raw material particle size D50=14.5, D90=30.7), with different prescriptions, granulate.Prescription is as follows:
| Supplementary material title | Prescription one | Prescription two | Prescription three |
| Isradipine | 5.0 g | 5.0g | 5.0g |
| Pregelatinized Starch | 50g | 50g | 50g |
| Microcrystalline Cellulose | 20 g | 20 g | 20 g |
| Carboxymethylstach sodium | 5 g | 10g | 10g |
| Sodium lauryl sulphate | —— | 5 g |
Get after above-mentioned different prescription takes supplementary material mix homogeneously, add 3% povidone solution and granulate, filled capsules respectively after dry granulate after dry granulate, with intelligent dissolution determination dissolution.Result is as follows:
Table 2 isradipine different prescription stripping curve measurement result
| Prescription | 15min | 30min | 45min | 60min |
| One | 46.7 | 54.3 | 60.3 | 64.7 |
| Two | 45.8 | 56.2 | 61.8 | 66.4 |
| Three | 50.8 | 60.3 | 65.7 | 70.5 |
These results suggest that employing prior art, change isradipine raw material particle size and prescription, the result of extraction of this product is not improved.
Embodiment 1: a kind of isradipine capsule, prescription is as follows:
Isradipine 5.0g
Pregelatinized Starch 50.0g
Microcrystalline Cellulose 20.0g
PVP K30 10.0g
Magnesium stearate 1.0g
Ethanol 65g
Make: 1000 capsules;
Preparation method is as follows:
A, get recipe quantity isradipine raw material and be dissolved in recipe quantity ethanol, then add PVP K30 stirring and dissolving;
B, get recipe quantity pregelatinized Starch and microcrystalline Cellulose is put in fluid bed, start blower fan, regulating air volume is good to fluidisation, and arranging inlet temperature is 35 ~ 40 DEG C, when temperature of charge rises to 25 DEG C, sprays into solution prepared by steps A and granulates;
C, obtained granule is crossed 30 mesh sieve granulate, add magnesium stearate, mix homogeneously, particles filled capsule after mixing.
Embodiment 2: a kind of isradipine capsule, prescription is as follows:
Isradipine 2.5g
Pregelatinized Starch 50.0g
Microcrystalline Cellulose 20.0g
PVP K30 5.0g
Magnesium stearate 1.0g
Ethanol 32.5g
Make: 1000 capsules;
Preparation method is as follows:
A, get recipe quantity isradipine raw material and be dissolved in recipe quantity ethanol, then add PVP K30 stirring and dissolving;
B, get recipe quantity pregelatinized Starch and microcrystalline Cellulose is put in fluid bed, start blower fan, regulating air volume is good to fluidisation, arranging inlet temperature is 35 ~ 40 DEG C, when temperature of charge rises to 25 DEG C, spray into solution granulation prepared by steps A, control atomizing pressure and peristaltic pump rotating speed, continue after having granulated to be dried to moisture≤2%;
C, obtained granule is crossed 30 mesh sieve granulate, add magnesium stearate, mix homogeneously, particles filled capsule after mixing.
Embodiment 1, embodiment 2 isradipine capsule stripping curve measurement result are as follows:
Table 3 isradipine stripping curve measurement result
| Embodiment | 15min | 30min | 45min | 60min |
| 1 | 75.8 | 95.4 | 96.7 | 98.8 |
| 2 | 76.2 | 93.5 | 98.6 | 100.4 |
The isradipine capsule accelerated stability that table 4 is prepared by the application's method investigates result
Can obviously be found out by the experimental data of above-described embodiment, the isradipine capsule prepared of prior art is about 60% at the dissolution of 60 minutes, isradipine capsule prepared by the application's method is about 99% at 60 minutes dissolutions, dissolution is significantly better than prior art, and in acceleration stability study in June, steady quality, this technology on the quality of product without impact.Achieve unforeseeable technique effect.
The present invention is not limited to aforesaid detailed description of the invention.The present invention expands to any new feature of disclosing in this manual or any combination newly, and the step of the arbitrary new method disclosed or process or any combination newly.
Claims (4)
1. a preparation method for isradipine capsule, is characterized in that, comprises the steps:
A, get recipe quantity isradipine raw material and be dissolved in recipe quantity ethanol, then add PVP K30 stirring and dissolving;
B, get recipe quantity pregelatinized Starch and microcrystalline Cellulose is put in fluid bed, start blower fan, regulating air volume is good to fluidisation, and arranging inlet temperature is 35 ~ 40 DEG C, when temperature of charge rises to 25 DEG C, sprays into solution prepared by steps A and granulates;
C, obtained granule is crossed 30 mesh sieve granulate, add magnesium stearate, mix homogeneously, particles filled capsule after mixing.
2. the preparation method of a kind of isradipine capsule as claimed in claim 1, is characterized in that: described isradipine capsule comprises the component of following parts by weight:
Isradipine 2.5-5.0 part;
Pregelatinized Starch 35-65 part;
Microcrystalline Cellulose 15-25 part;
PVP K30 8-12 part;
Magnesium stearate 0.5-1.5 part;
Ethanol 60-70 part;
Make: 1000 capsules.
3. the preparation method of a kind of isradipine capsule as claimed in claim 1 or 2, is characterized in that: in described step B, in pelletization, controls atomizing pressure 0.2 ~ 0.5mpa and peristaltic pump rotating speed 10 ~ 15r/min.
4. the preparation method of a kind of isradipine capsule as claimed in claim 1 or 2, is characterized in that: in described step B, continues to be dried to moisture≤2% after having granulated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510539483.7A CN105030726A (en) | 2015-08-30 | 2015-08-30 | Method for preparing isradipine capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510539483.7A CN105030726A (en) | 2015-08-30 | 2015-08-30 | Method for preparing isradipine capsule |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105030726A true CN105030726A (en) | 2015-11-11 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510539483.7A Pending CN105030726A (en) | 2015-08-30 | 2015-08-30 | Method for preparing isradipine capsule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105030726A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816263A (en) * | 1987-10-02 | 1989-03-28 | Alza Corporation | Dosage form for treating cardiovascular diseases comprising isradipine |
| CN104739770A (en) * | 2013-12-27 | 2015-07-01 | 上海睿智化学研究有限公司 | Nimodipine solid dispersant and tablet and their preparation methods |
| CN104784181A (en) * | 2015-03-26 | 2015-07-22 | 合肥华方医药科技有限公司 | Preparation method of pharmaceutical composition capable of increasing dissolution rate of indissolvable drug isradipine |
-
2015
- 2015-08-30 CN CN201510539483.7A patent/CN105030726A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816263A (en) * | 1987-10-02 | 1989-03-28 | Alza Corporation | Dosage form for treating cardiovascular diseases comprising isradipine |
| CN104739770A (en) * | 2013-12-27 | 2015-07-01 | 上海睿智化学研究有限公司 | Nimodipine solid dispersant and tablet and their preparation methods |
| CN104784181A (en) * | 2015-03-26 | 2015-07-22 | 合肥华方医药科技有限公司 | Preparation method of pharmaceutical composition capable of increasing dissolution rate of indissolvable drug isradipine |
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| PB01 | Publication | ||
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Application publication date: 20151111 |