CN102525997A - Moisture-proof coating citicoline sodium capsule and preparation method thereof - Google Patents
Moisture-proof coating citicoline sodium capsule and preparation method thereof Download PDFInfo
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- CN102525997A CN102525997A CN2012100770267A CN201210077026A CN102525997A CN 102525997 A CN102525997 A CN 102525997A CN 2012100770267 A CN2012100770267 A CN 2012100770267A CN 201210077026 A CN201210077026 A CN 201210077026A CN 102525997 A CN102525997 A CN 102525997A
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Abstract
The invention provides a moisture-proof coating citicoline sodium capsule and a preparation method thereof. The citicoline sodium capsule is composed of a capsule casing and quick-release moisture-proof micro pills or granules. All components in each capsule containing citicoline sodium quick-release moisture-proof micro pills or granules by percentage are 40% to 70% of citicoline sodium, 10% to 30% of microcrystalline cellulose, 10% to 30% of pregelatinized starch and 2% to 10% of moisture-proof coatings. The moisture-proof micro pills or granules are obtained by being extruded and rounded or pressed and granulated to be coated with moisture-proof coatings. The citicoline sodium capsule is good in moisture-proof function and resolves the problems that the capsule is prone to absorb water due to the fact that citicoline sodium is strong in moisture absorption, the capsule casing is prone to be fragile, and the like.
Description
Technical field
The present invention relates to a kind of moistureproof coating citicoline natrium capsule and preparation method thereof, belong to the pharmaceutical preparations technology field.
Background technology
C14H25N4NaO11P2 is used to treat craniocerebral injury and the caused neural sequela of cerebrovascular accident, and can be used for the treatment of parkinson, and senile dementia is also had certain curative effect; Other is as to slow down aging, and improving memory etc. also have the effect of improvement.C14H25N4NaO11P2 sees through blood brain barrier entering brain after getting into body, combines with the membrane phospholipid of brain cell, promotes the synthetic of membrane phospholipid, promotes the metabolism of brain, increases Mitochondrial ATPase and film Na
+/ K
+The activity of 2ATP enzyme, inhibition of phospholipase A
2Activity, increase brain norepinephrine and levels of dopamine, play stabilizing cell membrane, protection brain cell, reduce the effect that FFA and oxygen-derived free radicals discharge.Citicoline is as one of maximum neuron activation agent of clinical consumption, and curative effect and safety are through clinical confirmation for many years.
C14H25N4NaO11P2 is by Japan military field drugmaker exploitation, and 1967 with trade name " Nicholin " (Buddhist nun Kelin) listing, and in import China in 1988.Domestic listing preparation is injection type, conventional tablet or capsule.
C14H25N4NaO11P2 is prone to moisture absorption, and over-exposure easy moisture absorption in air causes sticking or influence to fill in citicoline natrium capsule filling process; And capsule is in put procedure, and the moisture in the capsule shells is absorbed by the citicoline granule in the softgel shell easily, causes capsule shells to become fragile; After packing, as adopt aluminum-plastic packagedly, the easy moisture absorption of granule causes moisture to increase.
Disclose C14H25N4NaO11P2 sheet and preparation method thereof among the Chinese patent file CN102028664, but do not related to the problem that C14H25N4NaO11P2 is prone to moisture absorption.Chinese patent file CN1260177 (CN98122857.7) discloses a kind of citicoline oral formulations and method for preparing, but the concrete component of clear and definite pharmaceutic adjuvant not, practicality is not strong.
Summary of the invention
To the deficiency of prior art, the present invention provides a kind of big moistureproof coating citicoline natrium capsule of producing and preparation method thereof that is fit to.Can avoid in the preparation process and capsule moisture varying in placing, can guarantee again in the capsule shells that moisture is not siphoned away and becomes fragile.
Technical scheme of the present invention is following:
A kind of citicoline natrium capsule; Contain moistureproof micropill of C14H25N4NaO11P2 rapid release or granule in every capsules; Moistureproof micropill of said C14H25N4NaO11P2 rapid release or granule are that the spraying moistureproof coating is processed on fast release micropill that makes with C14H25N4NaO11P2, microcrystalline Cellulose, pregelatinized Starch or granule, and each constituent mass percentage ratio is:
C14H25N4NaO11P2 40%-70%, microcrystalline Cellulose 10%-30%, pregelatinized Starch 10%-30%, moistureproof coating 2%-10%, each composition dosage sum is 100%.
According to the present invention, said moistureproof coating material is selected from Opadry, hydroxypropyl cellulose, hydroxypropyl emthylcellulose or acrylic resin.Wherein, the preferred moisture resistance Opadry of Opadry AMB, acrylic resin preferred acrylic resins E100.
According to the present invention, preferred, said citicoline natrium capsule prescription is formed as follows:
According to the present invention, preferred, said citicoline natrium capsule prescription is formed as follows:
The used main auxiliary material of citicoline natrium capsule of the present invention all can be buied in market.
According to the present invention, the capsular method for preparing of said C14H25N4NaO11P2 may further comprise the steps:
(1) 100 mesh sieves are pulverized, crossed to C14H25N4NaO11P2, pregelatinized Starch and microcrystalline Cellulose are crossed 40 mesh sieves respectively, and be subsequent use;
(2) by proportioning, the C14H25N4NaO11P2 after sieving, pregelatinized Starch and microcrystalline Cellulose are mixed, water is a wetting agent system soft material; Prepare micropill or granule with extruding spheronization; In 30-50 ℃ of oven dry, promptly get C14H25N4NaO11P2 fast release micropill or granule then;
Perhaps,
By proportioning, the C14H25N4NaO11P2 after sieving, pregelatinized Starch and microcrystalline Cellulose are mixed, dry-pressing is granulated, and gets the C14H25N4NaO11P2 immediate-release granules;
(3) by proportioning, get the moistureproof coating material and be mixed with the coating solution that solids content is 3-10wt%;
(4) C14H25N4NaO11P2 fast release micropill or the granule of getting step (2) place fluid bed, the coating solution of spraying step (3); Coating finishes the back and keeps fluidized state, continues dry 5-15min, promptly gets moistureproof fast release micropill of C14H25N4NaO11P2 or granule;
(5) with moistureproof fast release micropill of C14H25N4NaO11P2 or the particles filled capsule that in capsule shells, gets.
According to the method for the invention, preferred, the middle use of step (2) is extruded spheronizator and is prepared micropill or granule, rate of extrusion 20-30HZ is set, round as a ball rotating speed 300-500rpm, round as a ball time 30s-1min.
According to the method for the invention, preferred, process conditions are in the step (4): EAT is 40-60 ℃, and the air intake volume is 600-800m
3/ h, atomizing pressure are 1.0-1.5bar, and temperature of charge is 30-40 ℃, and coating solution spray speed is 60-120g/min.
Extrude spheronizator, the fluid bed etc. that use in the method for the invention described above are this area conventional equipment.
C14H25N4NaO11P2 capsule product hygroscopicity of the present invention is low, stable and controllable for quality, and preparation technology is suitable for big production, and the key process parameter scope is controlled, and effect duration is long.Compared with prior art, citicoline natrium capsule of the present invention has the following advantages:
1, adopt low adjuvant of hygroscopicity such as pregelatinized Starch, microcrystalline Cellulose is as filler and the disintegrating agent dry-pressing moistureproof clothing of back bag of granulating preferably with compressibility, it is good and be easy to disintegrate to obtain graininess.
2, after preparing fast release micropill or granule, spheronization wraps moistureproof clothing through extruding; Make under lower coating weightening finish condition; Just can guarantee good moisture-proof function and disintegration, in long-term 36 months study on the stability, moisture does not have obvious increase; Capsule shells does not have the phenomenon of becoming fragile, and product is stable, storage time is long.
The specific embodiment
It will be appreciated that; For those skilled in the art; In enforcement of the present invention, clearly and can be easy to make and do not deviate from other embodiment and the modification of the scope and the aim of the invention described above, all be included in protection scope of the present invention.Therefore, the scope that should not be construed as claims is limited in following examples.
Embodiment 1: prescription is formed:
Preparation technology:
100 mesh sieves are pulverized, crossed to the C14H25N4NaO11P2 of recipe quantity, and the pregelatinized Starch of recipe quantity and microcrystalline Cellulose are crossed 40 mesh sieves respectively, and be subsequent use; With the C14H25N4NaO11P2, pregelatinized Starch and the microcrystalline Cellulose that sieve and handle; Water is a wetting agent system soft material, the rate of extrusion 20-30HZ that extrudes spheronizator is set, round as a ball rotating speed 300rpm; Round as a ball time 30s; Prepare granule with extruding spheronization, 30-50 ℃ of oven dry, promptly get the C14H25N4NaO11P2 immediate-release granules then.
Get the moistureproof coating material Eudragit E 100 of recipe quantity, be mixed with the coating solution that solids content is 5wt%.Getting above-mentioned C14H25N4NaO11P2 immediate-release granules places fluid bed to carry out coating: EAT is 40-60 ℃, and the air intake volume is 600-800m
3/ h, atomizing pressure are 1.0-1.5bar, and temperature of charge is 30-40 ℃, and spray speed is 60-120g/min, and coating finishes the back and keeps fluidized state, continues dry 5-15min, promptly get the moistureproof immediate-release granules of C14H25N4NaO11P2; Be filled in and get capsule in the capsule.
Embodiment 2: prescription is formed:
Preparation technology
100 mesh sieves are pulverized, crossed to the C14H25N4NaO11P2 of recipe quantity, and the pregelatinized Starch of recipe quantity and microcrystalline Cellulose are crossed 40 mesh sieves respectively, and be subsequent use; With the C14H25N4NaO11P2, pregelatinized Starch and the microcrystalline Cellulose that sieve and handle; Water is a wetting agent system soft material, the rate of extrusion 20-30HZ that extrudes spheronizator is set, round as a ball rotating speed 500rpm; Round as a ball time 1min; Prepare micropill with extruding spheronization, 30-50 ℃ of oven dry, promptly get the C14H25N4NaO11P2 fast release micropill then.
Get the moistureproof coating material Ou Bada AMB of recipe quantity, be mixed with the coating solution that solids content is 10wt%.Getting above-mentioned C14H25N4NaO11P2 fast release micropill places fluid bed to carry out coating: EAT is 40-60 ℃, and the air intake volume is 600-800m
3/ h, atomizing pressure are 1.0-1.5bar, and temperature of charge is 30-40 ℃, and spray speed is 60-120g/min, and coating finishes the back and keeps fluidized state, continues dry 5-15min, promptly get the moistureproof fast release micropill of C14H25N4NaO11P2; Get capsule in the filled capsules shell.
Embodiment 3: prescription is formed:
Preparation technology:
100 mesh sieves are pulverized, crossed to C14H25N4NaO11P2, and pregelatinized Starch and microcrystalline Cellulose are crossed 40 mesh sieves respectively, and be subsequent use; With the C14H25N4NaO11P2, pregelatinized Starch and the microcrystalline Cellulose that sieve and handle, dry-pressing is granulated and is promptly got the C14H25N4NaO11P2 immediate-release granules.
Get the moistureproof coating powder of recipe quantity, be mixed with the coating solution that solids content is 3wt%.Getting above-mentioned C14H25N4NaO11P2 immediate-release granules places fluid bed to carry out coating: EAT is 50-70 ℃, and the air intake volume is 600-800m
3/ h, atomizing pressure are 1.0-1.5bar, and temperature of charge is 30-40 ℃, and spray speed is 60-200g/min, and coating finishes the back and keeps fluidized state, continues dry 5-15min, promptly get the moistureproof immediate-release granules of C14H25N4NaO11P2; Filled capsules gets capsule.
Embodiment 4:
Get respectively the foregoing description 1,2 and 3 the preparation the citicoline natrium capsule each 3 batches, embodiment 1 lot number: 081201,081202,081203; Embodiment 2 corresponding lot numbers: 090101,090102,090103; Embodiment 3 corresponding lot numbers: 090201,090202,090203.Measure moisture, dissolution, related substance, content labelled amount etc. (detection) according to WS-051 (x-047)-2002.The long-term placement after 36 months measured These parameters, and the result sees table 1 for details to 3.
36 months long-term stable experiment results of table 1 citicoline natrium capsule
36 months long-term stable experiment results of table 2 citicoline natrium capsule
36 months long-term stable experiment results of table 3 citicoline natrium capsule
The result shows: each batch of citicoline natrium capsule differences of the present invention is little, constant product quality is controlled.The long-term placement 36 months compared with 0 day under the 30 ℃/60%RH condition, and moisture and related substance slightly increase, but all up to specification, and other each item indexs have no significant change.
Claims (8)
1. citicoline natrium capsule; It is characterized in that containing in every capsules moistureproof micropill of C14H25N4NaO11P2 rapid release or granule; Moistureproof micropill of said C14H25N4NaO11P2 rapid release or granule are that the spraying moistureproof coating is processed on fast release micropill that makes with C14H25N4NaO11P2, microcrystalline Cellulose, pregelatinized Starch or granule, and each constituent mass percentage ratio is:
C14H25N4NaO11P2 40%-70%, microcrystalline Cellulose 10%-30%, pregelatinized Starch 10%-30%, moistureproof coating 2%-10%, each composition dosage sum is 100%.
2. citicoline natrium capsule according to claim 1 is characterized in that said moistureproof coating material is selected from Opadry, hydroxypropyl cellulose, hydroxypropyl emthylcellulose or acrylic resin.
3. citicoline natrium capsule according to claim 2 is characterized in that Opadry is moisture resistance Opadry AMB, and acrylic resin is an Eudragit E 100.
4. citicoline natrium capsule according to claim 1 is characterized in that, said citicoline natrium capsule prescription is formed as follows:
5. citicoline natrium capsule according to claim 1 is characterized in that, said citicoline natrium capsule prescription is formed as follows:
6. the capsular method for preparing of each said C14H25N4NaO11P2 of claim 1～5 may further comprise the steps:
(1) 100 mesh sieves are pulverized, crossed to C14H25N4NaO11P2, pregelatinized Starch and microcrystalline Cellulose are crossed 40 mesh sieves respectively, and be subsequent use;
(2) by proportioning, the C14H25N4NaO11P2 after sieving, pregelatinized Starch and microcrystalline Cellulose are mixed, water is a wetting agent system soft material; Prepare micropill or granule with extruding spheronization; In 30-50 ℃ of oven dry, get C14H25N4NaO11P2 fast release micropill or granule then; Perhaps,
By proportioning, the C14H25N4NaO11P2 after sieving, pregelatinized Starch and microcrystalline Cellulose are mixed, dry-pressing is granulated, and gets the C14H25N4NaO11P2 immediate-release granules;
(3) by proportioning, get the moistureproof coating material and be mixed with the coating solution that solids content is 3-10wt%;
(4) C14H25N4NaO11P2 fast release micropill or the granule of getting step (2) place fluid bed, the coating solution of spraying step (3); Coating finishes the back and keeps fluidized state, continues dry 5-15min, promptly gets moistureproof fast release micropill of C14H25N4NaO11P2 or granule;
(5) with moistureproof fast release micropill of C14H25N4NaO11P2 or the particles filled capsule that in capsule shells, gets.
7. like the capsular method for preparing of the said C14H25N4NaO11P2 of claim 6, it is characterized in that using in the step (2) and extrude spheronizator and prepare micropill or granule, rate of extrusion 20-30HZ is set, round as a ball rotating speed 300-500rpm, round as a ball time 30s-1min.
8. like the capsular method for preparing of the said C14H25N4NaO11P2 of claim 6, it is characterized in that process conditions are in the step (4): EAT is 40-60 ℃, and the air intake volume is 600-800m
3/ h, atomizing pressure are 1.0-1.5bar, and temperature of charge is 30-40 ℃, and coating solution spray speed is 60-120g/min.
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| CN 201210077026 CN102525997B (en) | 2012-03-21 | 2012-03-21 | Moisture-proof coating citicoline sodium capsule and preparation method thereof |
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| CN 201210077026 CN102525997B (en) | 2012-03-21 | 2012-03-21 | Moisture-proof coating citicoline sodium capsule and preparation method thereof |
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| CN102525997A true CN102525997A (en) | 2012-07-04 |
| CN102525997B CN102525997B (en) | 2013-07-17 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103509073A (en) * | 2013-08-29 | 2014-01-15 | 洪军 | Citicoline sodium compound |
| CN103830200A (en) * | 2012-11-21 | 2014-06-04 | 石药集团中奇制药技术（石家庄）有限公司 | Composition of 3-n-butylphthalide derivative, and preparation method thereof |
| CN106727377A (en) * | 2016-12-28 | 2017-05-31 | 江苏飞马药业有限公司 | A kind of tablet composition containing C14H25N4NaO11P2 main ingredient and preparation method thereof |
| CN106727415A (en) * | 2016-12-28 | 2017-05-31 | 江苏飞马药业有限公司 | A kind of capsule composition containing C14H25N4NaO11P2 and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101053572A (en) * | 2006-04-11 | 2007-10-17 | 中国医药研究开发中心有限公司 | Citicoline enteric coated preparation and its preparation method |
-
2012
- 2012-03-21 CN CN 201210077026 patent/CN102525997B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101053572A (en) * | 2006-04-11 | 2007-10-17 | 中国医药研究开发中心有限公司 | Citicoline enteric coated preparation and its preparation method |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830200A (en) * | 2012-11-21 | 2014-06-04 | 石药集团中奇制药技术（石家庄）有限公司 | Composition of 3-n-butylphthalide derivative, and preparation method thereof |
| CN103509073A (en) * | 2013-08-29 | 2014-01-15 | 洪军 | Citicoline sodium compound |
| CN103509073B (en) * | 2013-08-29 | 2016-01-06 | 洪军 | A kind of Citicoline sodium compound |
| CN106727377A (en) * | 2016-12-28 | 2017-05-31 | 江苏飞马药业有限公司 | A kind of tablet composition containing C14H25N4NaO11P2 main ingredient and preparation method thereof |
| CN106727415A (en) * | 2016-12-28 | 2017-05-31 | 江苏飞马药业有限公司 | A kind of capsule composition containing C14H25N4NaO11P2 and preparation method thereof |
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| CN102525997B (en) | 2013-07-17 |
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