CN112206214A - A pharmaceutical composition for treating hypertension - Google Patents
A pharmaceutical composition for treating hypertension Download PDFInfo
- Publication number
- CN112206214A CN112206214A CN202011226673.0A CN202011226673A CN112206214A CN 112206214 A CN112206214 A CN 112206214A CN 202011226673 A CN202011226673 A CN 202011226673A CN 112206214 A CN112206214 A CN 112206214A
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- CN
- China
- Prior art keywords
- nimodipine
- polyethylene glycol
- magnesium
- dodecyl sulfate
- aluminum silicate
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Abstract
The invention relates to a nimodipine pharmaceutical composition. The nimodipine tablet composition comprises 20-30 mg of nimodipine, 2-10 mg of hydroxypropyl cellulose, 1-4 mg of sodium dodecyl sulfate, 100 mg of magnesium aluminum silicate, 150 mg of lactose, 3-10 mg of crospovidone, 5-10 mg of croscarmellose sodium and 1-3 mg of magnesium stearate, and further comprises a certain amount of polyethylene glycol 4000, wherein the feeding mass ratio of the magnesium aluminum silicate to the polyethylene glycol 4000 is 1: 0.2-0.5. The invention provides a stable nimodipine tablet, which avoids the problem of rising of substances related to visible light.
Description
Technical Field
The invention relates to a nimodipine pharmaceutical composition, belonging to the technical field of pharmaceutical preparations.
Background
Hypertension is a traditional Chinese medicine risk factor for cerebral apoplexy, myocardial infarction, heart failure and chronic kidney disease, the death rate of hypertension caused by the hypertension in the world is over 700 thousands of cases each year, and the hypertension becomes one of the diseases with high human death cases.
Nimodipine (Nimodipine), also known as nifedipine (Nimotop), is a second generation of pyridine calcium antagonists, which was marketed by Bayer (Bayer) in 4 months in 1985. Since nimodipine has high lipophilicity, is easy to permeate blood brain barrier, has the functions of selectively dilating cerebral vessels and remarkably reversing artery spasm before basilar artery and spinal cord, nimodipine is clinically used for treating cerebrovascular diseases, namely ischemic cerebrovascular diseases, light or moderate hypertension, and preventing and treating cerebral vasospasm after subarachnoid hemorrhage, sudden deafness, migraine and the like, is a preferred medicament for treating cerebral vessels at present, and has high clinical application value particularly for senile dementia.
Nimodipine is insoluble in water and is easily degraded by light to cause the rise of related substances. The Chinese patent with the application number of 201310740199.7 discloses a nimodipine solid dispersant, a nimodipine tablet and a preparation method thereof, wherein povidone is used as a solid dispersion carrier, microcrystalline cellulose, starch, lactose and mannitol are used as filling agents, sodium carboxymethyl starch is used as a disintegrating agent, and the nimodipine solid dispersant, the nimodipine tablet and the preparation method thereof are prepared by a wet granulation process.
Disclosure of Invention
The purpose of the invention is as follows: the preparation method of the nimodipine tablet with simple process and stable quality is provided, and the problem that the nimodipine tablet is easy to degrade when exposed to light is solved.
The technical scheme of the invention is as follows:
a nimodipine tablet composition comprises 20-30 mg of nimodipine, 2-10 mg of hydroxypropyl cellulose, 1-4 mg of sodium dodecyl sulfate, 100 mg of magnesium aluminum silicate, 150 mg of lactose, 3-10 mg of crospovidone, 5-10 mg of croscarmellose sodium, 1-3 mg of magnesium stearate and a certain amount of polyethylene glycol 4000, wherein the feeding mass ratio of the magnesium aluminum silicate to the polyethylene glycol 4000 is 1: 0.2-0.5.
The aluminum magnesium silicate and the polyethylene glycol 4000 can well absorb the nimodipine solution in the rearrangement space of the aluminum magnesium silicate, and the problem that the nimodipine is easy to degrade when exposed to light is solved. When the feeding mass of the polyethylene glycol 4000 is less than 0.2 time of that of the magnesium aluminum silicate, the protection effect cannot be achieved; when the feeding mass of the polyethylene glycol 4000 is 0.5 times of that of the magnesium aluminum silicate, the dissolution rate of the prepared tablet is obviously reduced.
Preferably, each nimodipine tablet composition comprises 20-30 mg of nimodipine, 4-7.6 mg of hydroxypropyl cellulose, 1.5-3 mg of sodium dodecyl sulfate, 130 mg of magnesium aluminum silicate, 180 mg of lactose 110, 5-8 mg of crospovidone, 6-9 mg of croscarmellose sodium and 2 mg of magnesium stearate, and a certain amount of polyethylene glycol 4000, wherein the feeding mass ratio of the magnesium aluminum silicate to the polyethylene glycol 4000 is 1: 0.28-0.4.
The preparation method of the nimodipine tablet comprises the following steps:
firstly, weighing nimodipine and hydroxypropyl cellulose in the prescription amount, and dissolving in ethanol;
secondly, weighing the sodium dodecyl sulfate according to the prescription amount, dissolving the sodium dodecyl sulfate in purified water, adding the dissolved sodium dodecyl sulfate into the solution obtained in the first step, and stirring and mixing the solution uniformly;
thirdly, adding the solution obtained in the second step into a mixture of aluminum magnesium silicate, polyethylene glycol 4000 and crospovidone according to the prescription amount, and uniformly mixing;
and fourthly, adding the prescribed amount of lactose into the material obtained in the third step for granulation and drying.
And fifthly, adding the cross-linked sodium carboxymethyl cellulose and the magnesium stearate with the prescription amount into the granules obtained in the fourth step, mixing uniformly and tabletting.
And step seven, coating by adopting 10 percent of Carlekang coating powder aqueous solution, and controlling the weight gain of the coating to be 2-4 percent.
According to the preparation method, the aluminium magnesium silicate is adopted as the raw material, the polyethylene glycol 4000 is combined, the nimodipine solution is fully absorbed, and then the lactose granulation is adopted, so that the stability of the preparation is improved.
Has the advantages that:
the nimodipine solution can be well absorbed by adopting the aluminum magnesium silicate combined with the polyethylene glycol 4000, and the light-shielding effect is achieved to ensure the stability of the finished product under the illumination condition.
The invention provides a high-quality and low-cost composition for clinic, provides a stable tablet production technology for production enterprises, and avoids the occurrence of unsafe accidents of medicines.
Example (b):
example 1. nimodipine 20g, hydroxypropyl cellulose 2g, sodium dodecyl sulfate 2g, anhydrous alcohol 100g, water 10g, magnesium aluminum silicate 100g, polyethylene glycol 400020 g, crospovidone 3g, lactose 100g, croscarmellose sodium 5g, magnesium stearate 1g, the mass ratio of magnesium aluminum silicate to polyethylene glycol 4000 is 1: 0.2.
1000 tablets are prepared according to the preparation method of the technical scheme of the specification.
Example 2. nimodipine 20g, hydroxypropylcellulose 6g, sodium dodecylsulfate 3g, anhydrous ethanol 120g, water 10g, magnesium aluminum silicate 150g, polyethylene glycol 400045 g, crospovidone 6g, lactose 130g, croscarmellose sodium 6g, magnesium stearate 2g, the mass ratio of magnesium aluminum silicate to polyethylene glycol 4000 is 1: 0.3. 1000 tablets are prepared according to the preparation method of the technical scheme of the specification.
Example 3. nimodipine 30g, hydroxypropylcellulose 10g, sodium dodecylsulfate 4g, anhydrous ethanol 100g, water 10g, magnesium aluminum silicate 200g, polyethylene glycol 4000100 g, crospovidone 10g, lactose 150g, croscarmellose sodium 10g, magnesium stearate 2g, the mass ratio of magnesium aluminum silicate to polyethylene glycol 4000 is 1: 0.5. 1000 tablets are prepared according to the preparation method of the technical scheme of the specification.
Comparative example 1. nimodipine 20g, hydroxypropyl cellulose 6g, sodium dodecyl sulfate 3g, anhydrous alcohol 120g, water 10g, magnesium aluminum silicate 150g, polyethylene glycol 400010 g, crospovidone 6g, lactose 150g, croscarmellose sodium 6g, magnesium stearate 2g, the mass ratio of magnesium aluminum silicate to polyethylene glycol 4000 is 1: 0.067. 1000 tablets are prepared according to the preparation method of the technical scheme of the specification.
Comparative example 2. nimodipine 20g, hydroxypropyl cellulose 6g, sodium dodecyl sulfate 2g, anhydrous alcohol 120g, water 10g, magnesium aluminum silicate 150g, polyethylene glycol 4000150 g, crospovidone 6g, lactose 150g, croscarmellose sodium 6g, magnesium stearate 2g, the mass ratio of magnesium aluminum silicate to polyethylene glycol 4000 is 1: 1. 1000 tablets are prepared according to the preparation method of the technical scheme of the specification.
Test example 1
20 pieces of the products of examples 1 to 3 and comparative examples 1 to 2 were placed in a petri dish, placed in a light test chamber at a light intensity of 4500 + -500 LX, and sampled on days 5 and 10, respectively, to determine the contents of the substances (impurity I, maximum single impurity, total impurity) and the results are reported in tables 1 to 3.
TABLE 1 variation of impurity I under light conditions (4500. + -. 500 LX)
TABLE 2 maximum Single impurity Change under light conditions (4500. + -. 500 LX)
TABLE 3 Total impurity Change under light conditions (4500. + -. 500 LX)
Tables 1-3 data illustrate:
the products of examples 1 to 3 are shown in the present statement that, in the process of illumination, the change of related substances is relatively stable compared to the comparative example 1, which shows that a certain amount of magnesium aluminum silicate is combined with a certain amount of polyethylene glycol 4000 to produce a good light-shielding effect on nimodipine tablets, and the results of the comparative example 1 show that: when the feeding mass of the polyethylene glycol 4000 is less than 0.2 time of that of the aluminum magnesium silicate, related substances are obviously increased in the illumination process. With the increase of the feeding quality of the polyethylene glycol 4000, the change of related substances is relatively stable in the illumination process.
Test example 2
The dissolution curves of the products of the original study, examples 1-3 and comparative examples 1-2 were measured by means of a paddle method of 50 revolutions and 900ml of Ph4.5 acetate buffer containing 0.05% SDS, and the results are reported in Table 4.
TABLE 4 dissolution curves of pH4.5 acetate buffer
Table 4 the data illustrates:
the products of examples 1-3 of the invention have the same dissolution as the original reference preparation, and the dissolution of comparative example 1 is better than that of comparative example 2. The dissolution of the prepared tablet is basically not influenced when the feeding mass of the polyethylene glycol 4000 is less than 0.2 time of that of the aluminum magnesium silicate; when the feeding quality of the polyethylene glycol 4000 is higher than 0.5 time of that of the aluminum magnesium silicate, the dissolution of the prepared tablets is influenced.
Claims (3)
1. The nimodipine tablet composition is characterized in that each nimodipine tablet comprises 20-30 mg of nimodipine, 2-10 mg of hydroxypropyl cellulose, 1-4 mg of sodium dodecyl sulfate, 100 mg of magnesium aluminum silicate, 200 mg of lactose, 100 mg of lactose, 3-10 mg of crospovidone, 5-10 mg of croscarmellose sodium and 1-3 mg of magnesium stearate, and further comprises a certain amount of polyethylene glycol 4000, wherein the feeding mass ratio of the magnesium aluminum silicate to the polyethylene glycol 4000 is 1: 0.2-0.5.
2. The nimodipine tablet composition as claimed in claim 1, wherein each nimodipine tablet comprises 20-30 mg nimodipine, 4-7.6 mg hydroxypropyl cellulose, 1.5-3 mg sodium dodecyl sulfate, 130 mg magnesium aluminum silicate and 180 mg magnesium silicate, 110 mg lactose and 138 mg crospovidone, 5-8 mg croscarmellose sodium and 6-9 mg magnesium stearate, and a certain amount of polyethylene glycol 4000, wherein the mass ratio of the magnesium aluminum silicate to the polyethylene glycol 4000 is 1: 0.28-0.4.
3. A process for preparing a nimodipine tablet composition as claimed in claim 1, which comprises the steps of:
firstly, weighing nimodipine and hydroxypropyl cellulose in the prescription amount, and dissolving in ethanol;
secondly, weighing the sodium dodecyl sulfate according to the prescription amount, dissolving the sodium dodecyl sulfate in purified water, adding the dissolved sodium dodecyl sulfate into the solution obtained in the first step, and stirring and mixing the solution uniformly;
step three, adding the solution obtained in the step two into a mixture of aluminum magnesium silicate, polyethylene glycol 4000 and crospovidone according to the prescription amount, and uniformly mixing;
fourthly, adding lactose with the prescribed amount into the material obtained in the third step for granulation and drying;
fifthly, adding the cross-linked sodium carboxymethyl cellulose and the magnesium stearate with the prescription amount into the granules obtained in the fourth step, mixing uniformly and tabletting;
and step seven, coating by adopting 10 percent of Carlekang coating powder aqueous solution, and controlling the weight gain of the coating to be 2-4 percent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011226673.0A CN112206214A (en) | 2020-11-06 | 2020-11-06 | A pharmaceutical composition for treating hypertension |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011226673.0A CN112206214A (en) | 2020-11-06 | 2020-11-06 | A pharmaceutical composition for treating hypertension |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112206214A true CN112206214A (en) | 2021-01-12 |
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ID=74058402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011226673.0A Pending CN112206214A (en) | 2020-11-06 | 2020-11-06 | A pharmaceutical composition for treating hypertension |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112206214A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1013271A2 (en) * | 1998-12-15 | 2000-06-28 | Oscar Gold | Nimodipine tablets |
| 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 |
| CN107753458A (en) * | 2017-11-19 | 2018-03-06 | 北京元延医药科技股份有限公司 | Nimodipine tablet pharmaceutical composition and preparation method |
| CN111743872A (en) * | 2020-07-15 | 2020-10-09 | 迪沙药业集团有限公司 | Levamlodipine besylate composition |
-
2020
- 2020-11-06 CN CN202011226673.0A patent/CN112206214A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1013271A2 (en) * | 1998-12-15 | 2000-06-28 | Oscar Gold | Nimodipine tablets |
| 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 |
| CN107753458A (en) * | 2017-11-19 | 2018-03-06 | 北京元延医药科技股份有限公司 | Nimodipine tablet pharmaceutical composition and preparation method |
| CN111743872A (en) * | 2020-07-15 | 2020-10-09 | 迪沙药业集团有限公司 | Levamlodipine besylate composition |
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| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20210909 Address after: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province Applicant after: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Address before: No.1 Qingdao South Road, Weihai Economic and Technological Development Zone, Shandong Province Applicant before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Applicant before: Dijia Pharmaceutical Group Co.,Ltd. |
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| TA01 | Transfer of patent application right | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210112 |
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| WD01 | Invention patent application deemed withdrawn after publication |