CN105456230A - Method for preparing vitamin sustained release microsphere liquid-charging capsules - Google Patents
Method for preparing vitamin sustained release microsphere liquid-charging capsules Download PDFInfo
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- CN105456230A CN105456230A CN201510006275.0A CN201510006275A CN105456230A CN 105456230 A CN105456230 A CN 105456230A CN 201510006275 A CN201510006275 A CN 201510006275A CN 105456230 A CN105456230 A CN 105456230A
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Abstract
The invention relates to a method for preparing vitamin sustained release microsphere liquid-charging capsules. The method is characterized by including the steps that vitamins are dissolved into a release regulating agent ethanol solution, a proper quantity of emulsifying agent, a proper quantity of pore forming agent and a proper quantity of modifiers are added, the mixture is stirred, heated to 65 DEG C and emulsified for 2-4 h, solvents are washed away, and vitamin microspheres are prepared; then an auxiliary material is added to prepare a suspension, the suspension is poured into hard hollow capsules, and the capsules are prepared. The method is simple in technology and moderate in condition, severe conditions such as high temperature are avoided, and the biological activity of the vitamins can be guaranteed; a sustained-release technology and a liquid charging technology are used, the disadvantages of the poor stability, the short in-vivo half-life period, the volatility and the like of the vitamins can be overcome, and dosing times can be reduced; in addition, the medicine efficacy effect is even, safety is high, and a certain blood concentration can be maintained for a long time; hard capsule pouring is adopted, bonding caused when outer capsule membranes of soft capsules are broken and oil leaks can be avoided, the cost of devices and the like is reduced, and the capsules are easy to process and convenient to use and popularize.
Description
Technical field
The invention belongs to preparation technique field, be specifically related to a kind of preparation method of vitamin slow-releasing microsphere liquid-filling capsule.
Background technology
Vitamin is the micro-nutrient composition required for organism, and generally cannot be generated by organism oneself, needs to be obtained by means such as diet.Vitamin can not can produce power as saccharide, protein and fat, composition cell, but they play regulatory role the metabolism of organism.Most people, because single, the digestive system disease of food or to take in fat mass very few thus affect the absorption of fatsoluble vitamin, cause body to be deficient in vitamin; Gestation and women breast-feeding their children, child, special work post, crowd under special environment, vitamin needs amount increases relatively.Be deficient in vitamin and can cause serious health problem, appropriate picked-up vitamin can keep health in vigorous health, and excess ingestion vitamin but can cause poisoning.
Along with social development and people's living standard improve constantly, the mankind also have the development of advancing by leaps and bounds in the medical skill of preventing and curing diseases, in pharmaceutical preparation by original ordinary preparation to different characteristics preparation future developments such as quick-acting, long-acting, slow release.
Current vitamine capsule adopts soft capsule mostly, take Serum Vitamin concentration in rear a period of time can rise fast, Serum Vitamin concentration over-standard may be caused, newly old the thanking of body so can be caused to get muddled for a long time, unhealthful problem, and soft capsule needs daily repeatedly, takes number of times too much.Adopt slow release method prepare slow release vitamin microspheres capsule, can times for spraying be reduced, and Serum Vitamin concentration can be made to maintain certain level, avoid occur " entirely having " or " completely without " phenomenon.Vitamine soft capsule can because outer capsular rupture leakage of oil etc. cause occurring bonding situation, and adopt hard capsule embedding that this kind of situation can be avoided to occur.
Microsphere belongs to multiple-unit drug delivery system, has the following advantages: (1) medicine can be evenly dispersed in gastric, thus reduces individual variation; (2) after avoiding administration under one's belt occur " entirely having " or " completely without " phenomenon; (3) medicine is made microsphere by certain rate of releasing drug to take, treatment concentration can be reached fast, and maintain this level.Therefore there is better development prospect.
At present, the most frequently used preparation method of microsphere is solvent diffuse-volatility process, be divided into O/O type, O/W type, w/o type and W/O/W type, O/W/O type multi-emulsion method, the preparation of first two method is commonly used for insoluble drug, typical process flow is first by medicine dissolution or in being distributed to containing carrier volatile solvent, again the solution of formation or suspension are joined in the continuous phase containing emulsifying agent, then except desolventizing, obtain microsphere.Whole preparation process is simple, and process equipment drops into less.
Liquid-filling capsule is a kind of Novel capsule preparation developed in recent years.The structure of this capsule is traditional two-segment type, adopt gelatin or hydroxypropyl emthylcellulose shell, in softgel shell, do not add plasticizer, therefore migration is less likely to occur medicine, it discharges with the solid dosage forms liquid of novel concept, is called as " the desirable container of liquid and semi-solid preparation ".Liquid-filling capsule this be rich in the popularization of characteristic medicine-feeding technology, the existing product line of enterprise expansion can not only be made, also can meet the requirement of consumer to product " convenience ", " attractive in appearance ".
Adopt liquid-filling capsule technology, take inherently liquid mode, more multiple benefit can be brought: 1, be made up of natural colloid in liquid-filling capsule, fast the nutritional labeling of liquid state can be discharged, allow well the more effective absorption of health, the bioavailability of nutritional labeling can be made greatly to promote; 2, liquid-filling capsule can better be avoided decomposing degeneration by blocking oxygen, better protects the effectiveness of nutritional labeling; 3, liquid-filling capsule is easily swallowed and can better be covered up taste or bad smell; 4, the liquid parts of flowing in capsule can be seen in liquid-filling capsule, can provide and there is visual attraction.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of vitamin slow-releasing microsphere liquid-filling capsule.
The present invention is achieved through the following technical solutions:
A preparation method for vitamin slow-releasing microsphere liquid-filling capsule, its feature comprises the steps:
(1) vitamin is dissolved in the mixing release regulator alcoholic solution of hydroxypropyl emthylcellulose and polyacrylic resin with 1:1-5 ratio, stirs;
(2) add appropriate emulsifying agent, porogen and modifier, stir and be warming up to 65 DEG C of emulsifyings;
(3) after emulsifying 2-4h, solvent is washed away, obtained vitamin microsphere;
(4) add adjuvant and be made into suspension, embedding enters hollow and hard capsule and makes.
Release regulator described in the present invention is one or more of No. 1, polyacrylic resin, No. 2, polyacrylic resin and hydroxypropyl emthylcellulose (HPMC), the mixture of No. 1, optimization polypropylene acid resin and hydroxypropyl emthylcellulose (HPMC), its ratio is 1:1-20, preferred 1:1-10.
The consumption of release regulator described in the present invention and vitamin ratio are 1-5:1.
The preferred fatsoluble vitamin of vitamin described in the present invention, as vitamin A, vitamin D, vitamin E, vitamin K etc.
Emulsifying agent described in the present invention is gelatin, glycerol, Tween 80, polysorbate60, polysorbas20, preferably wherein one or more, and described emulsifier is 1-15%, preferred 1-5%.
Porogen described in the present invention is PVP, PEG, PVA, preferred PEG, more preferably PEG6000, and described porogen consumption is 1-20%, preferred 5-10%.
Modifier described in the present invention is magnesium stearate, Pulvis Talci, preferred magnesium stearate, and described magnesium stearate consumption is 0.5%-10%, preferred 0.5-2%.
Adjuvant described in the present invention is the mixture of edible oil, gelatin and appropriate amount of PEG 400 or PEG600, and its consumption is 10%-100%.。
The preferred plant of Capsules described in the present invention capsule.
Compared with existing vitamine soft capsule, beneficial effect of the present invention is:
(1) the present invention obtains vitamin microsphere by O/W emulsion process, adds adjuvant and is made into suspension, and envelope pours into obtained vitamin slow-releasing microsphere liquid-filling capsule in Capsules.This method technique is simple, easy to operate, and equipment cost is low, and organic reagent toxicity used is extremely low, volatile, little to human body side effect.It can avoid occurring that capsular rupture leakage of oil as outer in vitamine soft capsule causes the situations such as bonding, and vitamin microsphere has good slow release characteristic.
(2) vitamin is prepared into sustained-release micro-spheres by the present invention, and I, the shortcomings such as the poor stability of vitamin own, Half-life in vivo are short, changeableness can be overcome; II, can times for spraying be reduced, and make potent effects even, avoid occurring that vitamin content is too high, high safety, certain blood drug level can be maintained for a long time; III, add polyacrylic resin, can decompose in certain circumstances making microsphere, there is target administration.
(3) the present invention adopts liquid-filling capsule technology, and I, the bioavailability of vitamin can be improved; II, can better vitamin be avoided to decompose degeneration by blocking oxygen, better protect the effectiveness of its nutritional labeling; III, visual attraction can be provided.
(4) the vitamin slow-releasing microsphere that obtains of the present invention, is greater than 40%, 10h during its release rate 4h and is greater than 80%.
(5) vitamin slow-releasing microsphere of the present invention meets 2010 editions pharmacopeia to the release request of microsphere.
Accompanying drawing explanation
Fig. 1 is vitamin E microsphere scanning electron microscope diagram prepared by embodiment 3.
Fig. 2 is the vitro release-release time curve chart of the vitamin E sustained-release micro-spheres liquid-filling capsule prepared of embodiment and vitamin E soft capsule reference substance.
Detailed description of the invention
Below in conjunction with embodiment, embodiment of the present invention are described in detail, below embodiment be only limitted to the present invention is described, and should not be considered as limiting scope of the present invention.
Embodiment 1
Preparation: take release regulator (ratio of polyacrylic resin and HPMC is 1:1) 370g, be dissolved in 500ml alcoholic solution, stirring and evenly mixing, add 370g vitamin E powder, stirring adds emulsifying agent 150g (accounting for 15%), PEG90g (accounting for 9%), magnesium stearate 20g (accounting for 2%), stirring washes away solvent by purified water after being warming up to 65 DEG C of emulsifying 2h, obtains vitamin E microsphere.Get obtained microsphere 500g, by 1# capsule standard (1# capsule volume 0.5ml, its amount containing vitamin E is 50mg) carry out capsule-filling, calculate add adjuvant (calculating with edible oil density 0.8g/ml) amount for 2150ml, stirring and evenly mixing, in capsule filling and sealing machine, carry out embedding, obtain vitamin E sustained-release micro-spheres liquid-filling capsule.
Embodiment 2
Preparation: take release regulator (ratio of polyacrylic resin and HPMC is 1:3) 520g, be dissolved in 500ml alcoholic solution, stirring and evenly mixing, add 260g vitamin E powder, stirring adds emulsifying agent 120g(and accounts for 12%), PEG80g(accounts for 8%), magnesium stearate 20g(accounts for 2%), stirring washes away solvent by purified water after being warming up to 65 DEG C of emulsifying 2h, obtains vitamin E microsphere.Get obtained microsphere 500g, by 1# capsule standard (1# capsule volume 0.5ml, its amount containing vitamin E is 50mg) carry out capsule-filling, calculate add adjuvant (calculating with edible oil density 0.8g/ml) amount for 1350ml, stirring and evenly mixing, in capsule filling and sealing machine, carry out embedding, obtain vitamin E sustained-release micro-spheres liquid-filling capsule.
Embodiment 3
Preparation: take release regulator (ratio of polyacrylic resin and HPMC is 1:5) 615g, be dissolved in 500ml alcoholic solution, stirring and evenly mixing, add 205g vitamin E powder, stirring adds emulsifying agent 100g(and accounts for 10%), PEG70g(accounts for 7%), magnesium stearate 15g(accounts for 1.5%), stirring washes away solvent by purified water after being warming up to 65 DEG C of emulsifying 2h, obtains vitamin E microsphere.Get obtained microsphere 500g, by 1# capsule standard (1# capsule volume 0.5ml, its amount containing vitamin E is 50mg) carry out capsule-filling, calculate add adjuvant (calculating with edible oil density 0.8g/ml) amount for 950ml, stirring and evenly mixing, in capsule filling and sealing machine, carry out embedding, obtain vitamin E sustained-release micro-spheres liquid-filling capsule.
Embodiment 4
Preparation: take release regulator (ratio of polyacrylic resin and HPMC is 1:7) 688g, be dissolved in 500ml alcoholic solution, stirring and evenly mixing, add 172g vitamin E powder, stirring adds emulsifying agent 70g(and accounts for 7%), PEG60g(accounts for 6%), Pulvis Talci 10g(accounts for 1%), stirring washes away solvent by purified water after being warming up to 65 DEG C of emulsifying 2h, obtains vitamin E microsphere.Get obtained microsphere 500g, by 1# capsule standard (1# capsule volume 0.5ml, its amount containing vitamin E is 50mg) carry out capsule-filling, calculate add adjuvant (calculating with edible oil density 0.8g/ml) amount for 680ml, stirring and evenly mixing, in capsule filling and sealing machine, carry out embedding, obtain vitamin E sustained-release micro-spheres liquid-filling capsule.
Embodiment 5
Preparation: take release regulator (ratio of polyacrylic resin and HPMC is 1:9) 750g, be dissolved in 500ml alcoholic solution, stirring and evenly mixing, add 150g vitamin E powder, stirring adds emulsifying agent 50g(and accounts for 5%), PEG50g(accounts for 5%), magnesium stearate 5g(accounts for 0.5%), stirring washes away solvent by purified water after being warming up to 65 DEG C of emulsifying 2h, obtains vitamin E microsphere.Get obtained microsphere 500g, by 1# capsule standard (1# capsule volume 0.5ml, its amount containing vitamin E is 50mg) carry out capsule-filling, calculate add adjuvant (calculating with edible oil density 0.8g/ml) amount for 500ml, stirring and evenly mixing, in capsule filling and sealing machine, carry out embedding, obtain vitamin E sustained-release micro-spheres liquid-filling capsule.
The discriminating of embodiment 6 vitamin E microsphere:
The microsphere powder that each Example 1,2,3,4,5 washes away solvent gained is pasted on microscope slide uniformly, with electron microscope observation, see and form microsphere situation, the microsphere surface of result display embodiment 3,4,5 has gauffer and granular adsorption thing, has no micropore and crackle; The microsphere particle rounding of embodiment 1,2, there is crackle on surface.
The detection of embodiment 7 vitamin E sustained-release micro-spheres rate of release:
The vitamin E liquid-filling capsule that each Example 1,2,3,4,5 is obtained and vitamin E soft capsule one example, with simulated intestinal fluid 100ml for medium, temperature is 37.5 DEG C, with the 12h time for benchmark, sample in different time points, by Vitamin E levels in gas chromatography determination solution, calculate the Accumulation dissolution of each time point.
Table 1: the cumulative release percentage rate (%) of different sample
| Sequence number | 0.5h | 1h | 1.5h | 2h | 4h | 6h | 8h | 10h | 12h |
| Reference substance | 24.99 | 54.97 | 85.50 | 99.50 | |||||
| Embodiment 1 | 30.00 | 53.23 | 84.80 | 99.20 | |||||
| Embodiment 2 | 22.53 | 27.46 | 34.07 | 40.46 | 66.40 | 98.90 | |||
| Embodiment 3 | 18.95 | 28.32 | 36.20 | 43.22 | 53.27 | 67.56 | 84.49 | 96.35 | 99.50 |
| Embodiment 4 | 17.63 | 25.41 | 32.79 | 38.29 | 45.13 | 61.03 | 70.44 | 81.55 | 93.70 |
| Embodiment 5 | 8.95 | 11.46 | 14.10 | 16.85 | 28.55 | 39.30 | 46.33 | 55.79 | 62.10 |
Claims (9)
1. a preparation method for vitamin slow-releasing microsphere liquid-filling capsule, its feature comprises the steps:
(1) vitamin is dissolved in the mixing release regulator alcoholic solution of hydroxypropyl emthylcellulose and polyacrylic resin with 1:1-5 ratio, stirs;
(2) add appropriate emulsifying agent, porogen and modifier, stir and be warming up to 65 DEG C of emulsifyings;
(3) after emulsifying 2-4h, wash away solvent, obtain vitamin microsphere;
(4) add adjuvant and be made into suspension, embedding enters hollow and hard capsule and makes.
2. preparation method according to claim 1, it is characterized in that, described release regulator is one or more of polyacrylic resin I number, polyacrylic resin II number and hydroxypropyl emthylcellulose (HPMC), the mixture of optimization polypropylene acid resin I number and hydroxypropyl emthylcellulose (HPMC), its ratio is 1:1-20, preferred 1:1-10.
3. preparation method according to claim 1, is characterized in that, described release regulator consumption and vitamin ratio are 1-5:1.
4. preparation method according to claim 1, is characterized in that, the preferred fatsoluble vitamin of described vitamin, as vitamin A, vitamin D, vitamin E, vitamin K etc.
5. preparation method according to claim 1, is characterized in that, described emulsifying agent is gelatin, glycerol, Tween 80, polysorbate60, polysorbas20, preferably wherein one or more, and described emulsifier is 1-15%, preferred 1-5%.
6. preparation method according to claim 1, is characterized in that, described porogen is PVP, PEG, PVA, preferred PEG, more preferably PEG6000, and described porogen consumption is 1-20%, preferred 5-10%.
7. preparation method according to claim 1, is characterized in that, described modifier is magnesium stearate, Pulvis Talci, preferred magnesium stearate, and described magnesium stearate consumption is 0.5%-10%, preferred 0.5-2%.
8. preparation method according to claim 1, is characterized in that, described adjuvant is the mixture of edible oil, gelatin and appropriate amount of PEG 400 or PEG600, and its consumption is 10%-100%.
9. preparation method according to claim 1, is characterized in that, described Capsules preferred plant capsule.
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| CN201510006275.0A CN105456230A (en) | 2015-01-07 | 2015-01-07 | Method for preparing vitamin sustained release microsphere liquid-charging capsules |
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| CN201510006275.0A CN105456230A (en) | 2015-01-07 | 2015-01-07 | Method for preparing vitamin sustained release microsphere liquid-charging capsules |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107744147A (en) * | 2017-10-21 | 2018-03-02 | 刘滨 | A kind of cellulose base spacetabs type liposoluble vitamin piece and preparation method thereof |
| CN108144063A (en) * | 2017-12-25 | 2018-06-12 | 北京康比特体育科技股份有限公司 | A kind of preparation method of pellet liquid-filling capsule with Weight-reducing health |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1157690A1 (en) * | 2000-05-26 | 2001-11-28 | Pharma Pass LLC | Sustained release pharmaceutical composition |
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2015
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1157690A1 (en) * | 2000-05-26 | 2001-11-28 | Pharma Pass LLC | Sustained release pharmaceutical composition |
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| 孙清清: "pH敏感微球的制备及其控制释放性能", 《中国优秀硕士学位论文全文输数据库（工程科技I辑）》 * |
| 杨明等主编: "《药剂学》", 31 August 2014, 中国医药科技出版社 * |
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| 马家骅等: "充液胶囊的研究进展", 《中国中药杂志》 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107744147A (en) * | 2017-10-21 | 2018-03-02 | 刘滨 | A kind of cellulose base spacetabs type liposoluble vitamin piece and preparation method thereof |
| CN108144063A (en) * | 2017-12-25 | 2018-06-12 | 北京康比特体育科技股份有限公司 | A kind of preparation method of pellet liquid-filling capsule with Weight-reducing health |
| CN108144063B (en) * | 2017-12-25 | 2020-06-23 | 北京康比特体育科技股份有限公司 | Preparation method of pellet liquid-filled capsule with weight-losing and health-care functions |
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