CN1188114C - Edible coating composition - Google Patents

Edible coating composition Download PDF

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Publication number
CN1188114C
CN1188114C CNB008150168A CN00815016A CN1188114C CN 1188114 C CN1188114 C CN 1188114C CN B008150168 A CNB008150168 A CN B008150168A CN 00815016 A CN00815016 A CN 00815016A CN 1188114 C CN1188114 C CN 1188114C
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China
Prior art keywords
coating
coated composition
gram
microcrystalline cellulose
dosage forms
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Expired - Fee Related
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CNB008150168A
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Chinese (zh)
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CN1384736A (en
Inventor
M·奥吉洛
S·M·戴尔
D·C·图亚松
J·J·莫德理奇斯基
T·A·鲁斯卡
D·E·温纳
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FMC Corp
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FMC Corp
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Priority claimed from US09/491,724 external-priority patent/US6432448B1/en
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Publication of CN1188114C publication Critical patent/CN1188114C/en
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Classifications

    • 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
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • 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
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone

Abstract

An edible, hardenable coating composition containing microcrystalline cellulose and carrageenan and at least one of a strengthening polymer, a plasticizer, a surface active agent or a combination thereof. The coating composition of the present invention may be applied to pharmaceutical and veterinary solid dosage forms, confectionery, seeds, animal feed, fertilizers, pesticide tablets, and foods and provides an elegant prompt release coating which does not retard the release of active ingredients from the coated substrate.

Description

Edible coating composition
Invention field
The present invention relates to edible, can harden, the rapid release coated composition, these compositionss comprise microcrystalline Cellulose (MCC), chondrus ocellatus Holmes polysaccharide (CGN), and at least a reinforcement polymer or plasticizer.Coating of the present invention can be used for medicine (comprising nutrient drug) and veterinary drug solid preparation, confectionery, seed, animal feed, fertilizer, parasite killing tablet and granule, food.Coating of the present invention for example when being used as the coating of being taken in by the people, easily being scattered in the aqueous medium, and can obviously not postponing or prolong the release of active component in the substrate that is wrapped up.
Background of invention
It is a kind of common practice that medicine and beastly tablet dose are carried out coating, because can obtain some benefits like this, wherein have: cover offending active component taste with isolation coat, the apparent character that improves tablet makes it to be easier to swallow, reduce the absorption of tablet to water or dampness, because may reduce the activity of active component behind the tablet absorption moisture, cause that perhaps other disadvantageous variations take place tablet configuration, and just to obtaining the more good-looking tablet of outward appearance.
Another important function of medicine or beastly tablet dose coating is to improve the globality of tablet itself.Do not have the tablet of coating that wearing and tearing or cracked usually take place, in use can cause the loss of active component.What more kill is that they might break into two or several.A tolerance sign of useful coating is that it prevents that tablet configuration from the ability of above-mentioned any mechanical degradation taking place.Coating material prevents that tablet from wearing and tearing, effectiveness cracked or fracture can be tested with fragility and be measured.
Can wrap up confectionery and food by coated preparation, prevent that confection or food from contacting with dampness with airborne oxygen and go bad.Coating also can improve food appearance, improve the food organoleptic properties and do not lose its taste.
Seed can wrap up with coating, prevents to contact with dampness, thus the developmental capacity of protection seed.It also is a kind of method that increases particle diameter, makes things convenient for mechanical planting that seed is wrapped up.Can use dyestuff in the coated preparation, distinguishing the seed of different qualities, type, or as other labellings.Also usually comprise insecticide in the coated preparation,, can protect seed itself like this, also can protect from the longer seedling of seed as antifungal.In any case this coating can reduce the developmental capacity of seed anything but, after seed is planted in the soil, also cannot harm germination.
Animal feed can improve outward appearance by the increase flowability that is wrapped, opposing efflorescence or dirtization.In this class is used, can comprise vitamin, hormone, antibiotic or other analogous components in the coated preparation, to benefit the domestic animal of edible this feedstuff.
Fertilizer no matter be granule or tablet form, can wrap coating; to keep the integrity of fertilizer morphology; particularly can protect fertilizer not contact dampness,, thereby cause difficulty or inconvenience to quick in soil, uniform of application because dampness can make fertilizer agglomeration in storage.
Insecticidal preparation to the film-making agent carries out the integrity that coating can keep tablet or granule, and is just discrete rapidly after they place water, forms solution or serosity, thereby is applied in the soil or on the plant.The tablet that contains insecticide is carried out second of coating effect no less important, promptly prevent people's contact insecticide, thereby increased operation and use of insecticide process safe.
At present, the edible coating utilization of most commercial be a kind of synthetic cellulose polymer, as HYDROXY PROPYL METHYLCELLULOSE (HPMC).Other synthetic film former commonly used comprise ethyl cellulose, methylcellulose, polyvinyl pyrrolidone and dextrosan.These coating raw materials can use separately, also can with secondary film former, be used in combination as sodium alginate or propylene glycol alginate.Common and other combination of components uses of above-mentioned raw materials, described other components comprise filler, as lactose or maltodextrin; Plasticizer is as Polyethylene Glycol, dibutyl sebacate and triethyl citrate; Surfactant; Usually also have coloring material, as food dye or pigment, comprise opacifier, as titanium oxide and so on.
The process of the coated preparation that is used for spraying in preparation, the film former composition of other in preparation usually dissolves or is dispersed in the solvent, for example water.In water solution system, because many polymer need fully hydration of plenty of time, the preparation of coating usually must be carried out before it is used to wrap up tablet.General procedure is to prepare coating the previous day wrapping up operation, to guarantee the abundant hydration of used polymer.
Mainly the coating based on HPMC has a special disadvantage, and promptly coating may harden in time, thereby increases the disintegration time of tablet.The increase of disintegration of tablet time can delay the bioavailability of active component, and this delaying is directly proportional with the increase of disintegration time at least.Know, usually the many reagent of other that use in the coating component also can delay the release of medicament, as use the enteric coating (this type of enteric coating of part is specially selected to make tablet through the harmonization of the stomach small intestinal, discharges then) of the polymer film-forming material of water insoluble or gastric juice in colon.
Coating of the present invention meets the USP standard (American Pharmacopeia monograph 23) about active component quick or instantaneous stripping from the tablet that is wrapped with coating or other solid dosage formss.The speed of their rapid release or stripping is suitable with the normal rate of release of the tablet that does not have coating or other substrates.Therefore, they can not bring negative effect, perhaps can not delay active component and discharge from the substrate that is wrapped with coating.In addition, coating of the present invention disperses in the aqueous medium that puts on the coating substrate and the energy fast hydrating easily, and can provide profile refined coating, and they have all advantages of present commercial coating, and do not have their common shortcomings that exists.
Summary of the invention
We find, according to the present invention, above-mentioned and other advantage can realize by a kind of coated composition, and said composition comprises and is particularly suitable in aqueous medium or the combination of the material of the uniqueness that (for example being taken in by the people) back that is ingested discharges rapidly.Coated composition of the present invention comprises microcrystalline Cellulose, chondrus ocellatus Holmes polysaccharide, and at least a reinforcement polymer and plasticizer.More particularly, the invention provides a kind ofly can discharge rapidly, edible, hardenable coated composition, it comprises the microcrystalline Cellulose of 3%-40%, the ι chondrus ocellatus Holmes polysaccharide of 9%-25%, at least a reinforcement polymer, plasticizer or surfactant; The present invention also provides anhydrous coating and its aqueous dispersions of above-mentioned composition.
The present invention also provides medicine (comprising nutrient drug) and the veterinary drug solid preparation that is wrapped with rapid release of the present invention, edible, hardenable compositions, confectionery, seed, animal feed, fertilizer, parasite killing tablet and granule, and food.
Detailed Description Of The Invention
According to application purpose of the present invention, term " edible " means regulator and agrees as medicinal or edible food-grade material.The term that is used for describing coated composition of the present invention " can harden ", be intended to only to comprise those can be from its aqueous solution or dispersion liquid mummification become the coated composition of solid coating (coating promptly hardens), this solid coating can be resisted frictional force, be different from " being coated with sugar-coat " coating on the confection, the latter is made into to operate and to pack but can not significantly resists the Soft Roll clothing of frictional force.Be used to illustrate coated composition of the present invention or discharge, be meant that coating of the present invention meets about active component quick or instantaneous dissolved USP standard (American Pharmacopeia monograph 23) from the tablet that is wrapped with coating or other solid dosage formss with the dissolution rate of the tablet of present composition coating or the term of time " immediately ", " fast " or " rapidly ".The speed of their rapid release or stripping is suitable with the normal rate of release of the tablet that does not have coating or other substrates.Consistent with above-mentioned standards of pharmacopoeia, when they placed aqueous medium or are ingested (for example being taken in by the people), their not appreciable impacts or delay were wrapped with the release or the stripping of tablet or other solid preparations of above-mentioned coating.For example, according to the coating of the present invention preparation be ingested the back or be placed in the aqueous medium after, can be within 10 minutes basically or fully disintegrate and/or molten removing.Therefore, after a kind of solid dosage forms wrapped coating of the present invention and taken in by people or other animals, coating of the present invention just can stripping or disintegrate before leaving stomach.In the embodiment and claim of this description and back, all percent all is to calculate by the dry weight of compositions.Unless spell out in addition, above-mentioned definition is applicable to the application's full content.
Microcrystalline Cellulose can be processed with chondrus ocellatus Holmes polysaccharide, also can with its simple mixing, but can both have an effect with chondrus ocellatus Holmes polysaccharide, so that important film forming character to be provided, these film forming character are that the refined coating of preparation profile is desired, they are for example, be used for wrapping up contain in the medicine that after being placed in aqueous medium or being ingested, needs the active component that discharges rapidly or veterinary drug tablet, capsule, granule and the pill particularly useful.
Microcrystalline Cellulose is the cellulose of a kind of purification, part depolymerization, and is general by using mineral acid, salt acid treatment cellulosic material preferably, the chemical cellulose of preferably taking from the cellulosic plant and existing with pulpous state) produce.Acid is owed regular zone on the attack cellulosic polymer chain selectively, thereby exposes and vacate crystallite thing site, forms the crystallite thing aggregation that constitutes microcrystalline Cellulose.Subsequently these crystallite thing aggregations are separated from reactant mixture, washing is to remove degradation by-products.The wet thing that obtains (moisture that 40%-60% is arranged usually) has several names in this area, comprise hydrocellulose, microcrystalline Cellulose, the wet cake of microcrystalline Cellulose, or be called wet cake simply.The wet cake of this microcrystalline Cellulose can directly utilize at this point, also can further handle, and for example polishes and/or drying, is used according to the present invention then.
Being used for microcrystalline Cellulose of the present invention also can utilize the steam explosion processing to be prepared.In the method, wood chip or other cellulosic materials are placed a Room, feed superheated steam to this chamber then.After keeping about 1-5 minute, open air outlet valve fast, indoor material is discharged with the form of outburst, thereby produce microcrystalline Cellulose.Need not in reactant mixture, to add acid in addition, it is believed that this is because acidic materials and high temperature, high pressure in the wood chip have made cellulose generation hydrolysis and degraded.Except that the microcrystalline Cellulose of true-to-shape, the present invention also considers to use other cellulose derivatives, comprises that microgrid shape cellulose (also claiming microgrid shape microcrystalline Cellulose) and Powderd cellulose are (as commercially available prod " Solka Floc ").
As following will more talking out, among the present invention the mean diameter of the preferred microcrystalline Cellulose that uses less than about 100 microns, if grind little or mean diameter between the 1-50 micron then relatively good, then better between the 1-30 micron.
Chondrus ocellatus Holmes polysaccharide and microcrystalline Cellulose are used in combination, to form the refined coating with rapid release advantage of the present invention.The chondrus ocellatus Holmes polysaccharide that uses among the present invention is natural chondrus ocellatus Holmes polysaccharide, comprises different stage further defined below: ι (iota), κ (kappa) and λ (lambda) chondrus ocellatus Holmes polysaccharide.The preferred type of chondrus ocellatus Holmes polysaccharide is by galactose repetitive and 3, the polysaccharide that 6-galactose acid anhydride repetitive constitutes, and what promptly be applicable to the present composition is the ι chondrus ocellatus Holmes polysaccharide.The abundant source of ι chondrus ocellatus Holmes polysaccharide is the zostera marina of a kind of Eucheumaspinosum of being named as.The content of galactose acid anhydride is about 30% in the ι chondrus ocellatus Holmes polysaccharide, and the content of galactose acid anhydride is about 34% in the kappa carrageen glycan, and does not contain these unit substantially in the λ chondrus ocellatus Holmes polysaccharide.Another feature of chondrus ocellatus Holmes polysaccharide is the content of the sulfate group on galactose and galactose acid anhydride.The content of sulfuric ester is about 25%-34% in the ι chondrus ocellatus Holmes polysaccharide, preferably about 32%.This is between kappa carrageen glycan (sulfuric ester content is 25%) and λ chondrus ocellatus Holmes polysaccharide (sulfuric ester content is 35%).The sodium salt of ι chondrus ocellatus Holmes polysaccharide is dissolved in cold water, but the ι chondrus ocellatus Holmes polysaccharide of different stage need be heated to different temperatures with water so that its dissolving.Be applicable to that the ι chondrus ocellatus Holmes polysaccharide in microcrystalline Cellulose of the present invention/ι chondrus ocellatus Holmes polysaccharide raw material dissolves in the highest water that is heated to 80 ℃ (176).Other ι chondrus ocellatus Holmes polysaccharide of priority should be able to dissolve under lower temperature, and for example 50 ℃ (122 °F), this includes, but is not limited to ι chondrus ocellatus Holmes polysaccharide sodium salt.
In coated composition of the present invention, the consumption of chondrus ocellatus Holmes polysaccharide must be enough to be used for forming film.Suitable amounts that can film forming chondrus ocellatus Holmes polysaccharide is generally about 9%-25% (with the dry weight basis of coated composition), if between about 10%-20% (with the dry weight basis of coated composition) then more favourable.
Microcrystalline Cellulose and the chondrus ocellatus Holmes polysaccharide coprocessing of can putting together also can mix in any suitable manner, mixes as doing.
The microcrystalline Cellulose of coprocessing/ι chondrus ocellatus Holmes polysaccharide is peptizationization rapidly.Peptizationization is meant that dried reagent can easily be dispersed in the water, is colloidal state.The peptizationization of dried reagent in aqueous medium can make the functional restoration of reagent to approaching, perhaps better reaches reagent viewed level before drying.The peptization dried reagent can be with minimum dispersed with stirring (peptizationization) in colloidal state fast.Therefore, the coated preparation of novelty that has mixed the microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide of coprocessing can be in few hydration in 0.5 hour the time, but preferably requires to carry out in 1-3 hour hydration.Like this, under the situation of not damaging preparation, can save and put forward the practice for preparing coated preparation the previous day, if but this practice is favourable, also can keep it.If used in second day after the formulation preparation, must stir preparation for a moment before use, to recover its flow regime.
Being used for coprocessing microcrystalline Cellulose of the present invention/ι chondrus ocellatus Holmes polysaccharide can prepare like this: at first polish through the wet cake of the cellulose of hydrolysis, make the mean diameter of wet cake particle generally be no more than about 20 microns, less than about 10 microns better; The wet cake of polishing is dispersed in the water of heating, and water temperature is higher than makes the used required temperature of specific ι chondrus ocellatus Holmes polysaccharide dissolving; Dried chondrus ocellatus Holmes polysaccharide is added in the microcrystalline Cellulose dispersion liquid; Blending ingredients preferably makes mixture homogenization, to guarantee thorough mixing; Dry dispersion liquid; Spray drying often is used to preparation and is used for siccative of the present invention, but the additive method of dry dispersion liquid may be utilized equally.
Can be directly by wet cake dispersion liquid of microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide, by replenishing the water that is present in the wet cake and preparing coating other components (promptly before the dry wet cake) that in dispersion liquid, add in the preparation.Operation is favourable though this operational approach is for some coatings, is more prone to use spray-dried usually or through the exsiccant material of additive method, because the cost of transportation of dispersion liquid is very uneconomical.In addition, with the association that any method drying all can improve microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide, the coating that makes thus has the rapid releasing effect that makes us more satisfied.
We find, by dry mixed microcrystalline Cellulose (for example, Avicel PH-105,20 microns of mean diameters) and the coating of ι chondrus ocellatus Holmes polysaccharide preparation be equal at least, also be better than coated composition in some cases by microcrystalline Cellulose/chondrus ocellatus Holmes polysaccharide preparation of coprocessing.
When the aqueous dispersions of chondrus ocellatus Holmes polysaccharide sprays from the teeth outwards, and when making it drying, itself be exactly known natural film forming hydrocolloid.Yet, a little less than the film that is become is considered to too, be not suitable for tablet (seeing result shown in the Comparative Example A An), therefore require to use microcrystalline Cellulose to obtain satisfied result.
In Comparative Examples B, physics is done and is mixed ι chondrus ocellatus Holmes polysaccharide and microcrystalline Cellulose (for example, Avicel As if PH-102,100 microns of mean diameters) result who produces considers from commercial angle, can not be satisfactory.Therefore, for commercial object, it is believed that be used for doing the mean diameter of the microcrystalline Cellulose that mixes with natural film forming hydrocolloid should be below 100 microns, be lower than about 50 microns more favourable, between about 1-50 micron, be good, between about 1-30 micron better.The refined coated preparation of high-performance within the scope of the present invention can be done microcrystalline Cellulose and the chondrus ocellatus Holmes polysaccharide preparation that mixes by this physics.
In the present invention, the weight ratio of microcrystalline Cellulose that is adopted and chondrus ocellatus Holmes polysaccharide is 90: 10 to about 15: 85.The higher microcrystalline Cellulose of needs and chondrus ocellatus Holmes polysaccharide ratio (MCC: in the application CGN weight ratio), this ratio is generally about 90: 10 to about 60: 40, especially, from about 85: 15 to about 65: 35, more particularly, about 70: 30.In certain embodiments of the invention, discovery can be adopted more a spot of relatively microcrystalline Cellulose, like this, MCC: CGN can from about 15: 85 in 60: 40 scope, better up to 55: 45, best up to 50: 50.The ratio that it is microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide that physics is done a mixed good especially place can change easily by simple hybrid technology, and does not need the coprocessing material of synthetic different proportion.Therefore, physics is done and is mixed and can provide king-sized motility for the concrete application with different demands.Contain the medicine of given activity component and veterinary drug solid preparation and may need to increase chondrus ocellatus Holmes polysaccharide content in the compositions, so that better the parcel of tablet.For these application in medicine and veterinary drug, the preferable weight ratio of microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide is between about 75: 25 to 25: 75.
No matter compositions is based on the microcrystalline Cellulose/chondrus ocellatus Holmes polysaccharide of coprocessing and also is based on dried microcrystalline Cellulose and the chondrus ocellatus Holmes polysaccharide that mixes of physics, in coated preparation of the present invention, may there be a kind of reinforcement polymer (strengthening polymer) [hydroxyethyl-cellulose (HEC) or polyvinyl pyrrolidone (PVP) are better], perhaps a kind of plasticizer, perhaps reinforcement polymer and plasticizer and/or surfactant.
Can bring same benefits and can replace other reinforcement polymer of HEC to comprise HPMC, hydroxypropyl cellulose, ethyl cellulose and methylcellulose; But, must be careful when using these substitution material, in case significantly delay the release of active component and/or influence its bioavailability.The preferable use amount of reinforcement polymer should be less than the total amount of microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide in the compositions.According to the required hardness of coating, the reinforcement polymer use amount in the compositions can think that coating provides intensity on the level between about 0.5% to about 30%, and improves its outward appearance.This intensity can be measured by following method: on a noncohesive flat surface coated preparation is made film, the film that is become is cut into wide bar shaped, go up in tension force experimental machine (as Instron tension force experimental machine) then strip-shaped membrane is carried out tension test.These test results show that when comprising HEC or other reinforcement polymer in the preparation, the film forming hot strength of institute increases, and fragility reduces.Being applicable to the present invention and can significantly not delaying the reinforcement polymer of the rate of release of tablet or other forms of solid preparation, is these polymer, and under 20 ℃, its 2% viscosity in aqueous solution is equal to or less than the polymer of 20 milli handkerchief seconds.When preparation used the reinforcement polymer under without the situation of plasticizer when, the consumption of reinforcement polymer was about 5%-30% (with the dry weight basis of coated composition) usually.
For preparing compositions preferably, in coated composition, also should comprise traditional plasticizer.Suitable manufacturing methods comprises Polyethylene Glycol (Polyethylene Glycol that molecular weight is high is preferable), glycerol triacetate, dibutyl sebacate, polypropylene glycol, sorbitol, glycerol and triethyl citrate.Wherein polyvinyl alcohol is preferable.The amount of these used plasticizers can be 18% on about 36% level (with the dry weight basis of coated composition) in the coated composition of the present invention, best on 31% to 35% level (with the dry weight basis of coated composition).
Rapid release coated composition of the present invention can comprise at least a filler.This type of filler can comprise, for example, calcium carbonate, dicalcium phosphate and carbohydrate are as starch, maltodextrin, lactose, mannitol and other saccharides.Wherein, maltodextrin, mannitol and lactose are filleies preferably.
Rapid release coated composition of the present invention can comprise at least a surfactant.This surfactant can be anion surfactant or non-ionic surface active agent.Useful surfactant can be, for example, and sodium lauryl sulphate, hydroxylation soybean lecithin (lecithin), polysorbate (polysorbates), and polyoxypropylene-polyoxyethylene block copolymer.We find that lecithin is specially adapted in some coated composition of the present invention, and suitable consumption is (with the dry weight basis of coated composition) on the level between about 2% to about 10%.
Stain and opacifier also can be used in these coatings, or are added in their suspension.Stain and opacifier comprise aluminum color lake (aluminum lakes), insoluble pigment, water-soluble dye, titanium dioxide and Talcum.Can add about 1% stearic acid to about 5% (with the dry weight basis of compositions), or its salt, or its ester, to increase the gloss of coating, especially in compositions, do not use under the situation of plasticizer.Similarly, also can increase the gloss of coating by a spot of propylene glycol alginate of adding [about 5% to about 10% (with dry weight basis of coated composition)], shown in embodiment 31.
Coated preparation of the present invention can dry powder form or the i.e. form sale of usefulness aqueous dispersions.Aqueous dispersions is preferably in preparation under the aseptic condition.Before the preparation dispersion liquid, heat water to higher temperature (as 85 ℃), found that to prevent that at least 48 hours agar from pouring into antibacterial on the plate, mycete and zymic growth.Therefore, if the container of dress dispersion liquid is suitably cleaned, fill dispersion liquid then and seal needs up for safekeeping when using, grow in dispersion liquid so antibacterial, mycete or zymic probability are very little.Perhaps,, and a period of time to be stored, so also antiseptic can be added if the preparation of selling is an aqueous dispersions.In this respect, the combination of methyl hydroxybenzoate and propylparaben is found useful.
In dry weight percent, a better compositions of the present invention comprises at least 43%, and suitable is about 45% to about 75%, is more preferably about 45% to about 60% microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide (carrageenan) mixed-powder; About 0.5% to about 30%, is more preferably the reinforcement polymer of about 7-22%; About 25% to about 40%, is more preferably about 31% to about 35% plasticizer; About 2% to about 28% inert filler.Optional is, about 1% to about 30% preparation can comprise edible stain and opacifier (as Talcum or titanium dioxide), comprising from 1% to about dyeing component of 8%, preferably about 1% to about 3% (as food dye or pigment).Other any components can comprise about 0.5% to about 10%, and 0.5% to about 7% surfactant advantageously is if the filler of existence as maltodextrin or mannitol then is 1.25% preferable to 3%.If filler of no use, then the consumption of surfactant (as lecithin) can reach about 5% to about 20% level.Also can contain antiseptic in the preparation, methyl hydroxybenzoate as 0.75% to 1.50% and/or 0.075% to 0.15% propylparaben.If make filler with maltodextrin, its consumption is generally about 2% to about 7% (with dry weight basis of compositions); If make filler with mannitol, then its consumption is generally about 10% to about 25% (with dry weight basis of preparation).These filleies can be used singly or in combination in above-mentioned specified scope.
The amount of filler in these coated preparations is lower, particularly when opacifier is titanium dioxide, can use the stain of relatively small amount.Because stain is very expensive, so with respect to those need 6% to about 16% the effective painted preparation process of stain ability in the prior art of coated preparation, this greatly reduces cost.
Provide edible in interested other embodiments that the present invention can mention especially, can harden, the coated composition of rapid release, it comprises the combination of the ι chondrus ocellatus Holmes polysaccharide of 3% to 40% microcrystalline Cellulose and about 9% to about 25%, with at least a reinforcement polymer, plasticizer or surfactant, but wherein said coated composition fast hydrating, and when being ingested or being placed in the aqueous medium, can significantly not delay to be wrapped with the release of active component in the substrate of described coating.Here any reinforcement polymer of mentioning, plasticizer, surfactant, stain etc. may be used to this embodiment.
For instance, first kind of embodiment in these embodiments comprise a kind of edible, can harden, the coated composition of rapid release, it comprises about 5% to about 25%, particularly about microcrystalline Cellulose of 5% to 10%; About 10% to about 16%, concrete is about 14% to about 16% ι chondrus ocellatus Holmes polysaccharide.Such embodiment also can comprise about 2% to about 10% surfactant (as lecithin), about 35% to about 70% filler (as lactose as filler) and/or about 5% to about 10% propylene glycol alginate.These compositionss also can comprise 5% to 22% reinforcement polymer (as polyvinyl pyrrolidone or hydroxyethyl-cellulose).Also can use reinforcement mixture of polymers (as PVP and HEC).In addition, available about stain of 2% to 10% prepares the coated composition of colouring.These compositionss can also comprise at least a filler, as maltodextrin, dicalcium phosphate, cross-linking sodium carboxymethyl cellulose (croscarmellose sodium) and their mixture.In this embodiment, can reduce the consumption of microcrystalline Cellulose, use low quantity of surfactant simultaneously, and with high-load lactose as filler.The specific compositions of this class can comprise 5% to 10% microcrystalline Cellulose, 14% to 16% ι chondrus ocellatus Holmes polysaccharide, and 2% to 4% hydroxylation soybean lecithin, 65% to 70% lactose also can comprise about propylene glycol alginate of 5% to 10%.MCC in this embodiment: the CGN weight ratio can about 15: 85 in 60: 40 scope, perhaps more specifically, at 15: 85 to about 50: 50 in scope; And the combination total amount of microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide accounts for about 20% to about 40% of coated composition.When PVP was used as unique reinforcement polymer, its consumption level was better at about 5% to about 16% o'clock; And when HEC was used as unique reinforcement polymer, its consumption level was better at about 20% to about 22% o'clock.The object lesson of these implementation methods is set forth among the embodiment 36-53 of table 1 below.
Second kind of embodiment of coated composition of the present invention comprises about 30% to about 40%, particularly the microcrystalline Cellulose of about 33%-38%; About 10% arrive to about ι chondrus ocellatus Holmes polysaccharide of 20%, more particularly about 14% to about 17% and about 12% about 25%, the reinforcement polymer (as hydroxyethyl-cellulose) of about 12%-22% more particularly.These compositionss also can further comprise about 5% to about 10%, particularly the surfactant of 7-10% (as the hydroxylation soybean lecithin); About 8% to about 15% filler (as lactose, maltodextrin and combination thereof), more particularly about lactose of 5% to 10% and optional be from 5% to about 10% stain.In this embodiment, if make filler with maltodextrin, then its content is about 3% on about 5% level, and is about 3% particularly, and will with another kind of filler, 7% to about 10% according to appointment, more particularly about lactose of 8% to 9% is used in combination.Suitable variation comprises such some compositions: except MCC, outside CGN and the HEC, also comprise about 30% stain to about Polyethylene Glycol of 36%, more particularly about 34% to about 35% and about 4% to about 5%.In this group compositions, MCC: the CGN weight ratio can be in 64: 40 to 75: 35 scope, MCC and CGN to close heavy can be about 48% weight to about 60% weight (with composition weight meter).Be also pointed out that the present embodiment can contain a kind of suitable stain.This embodiment is shown in the embodiment 54-57 of following table 1.
At last, the third embodiment of the present composition comprises 30% to 40%, particularly about 33% to about 38% microcrystalline Cellulose; About 10% to about 20%, more particularly about 13% to about 16%.The ι chondrus ocellatus Holmes polysaccharide; About 10% to about 15% reinforcement polymer (as polyvinyl pyrrolidone); 30% to 40%, 33% to 36% plasticizer (as Polyethylene Glycol) more particularly.This embodiment also can comprise about 2% to about 10% stain.In this embodiment, MCC: the CGN weight ratio can about 60: 40 in about 75: 25 scope, MCC and CGN close the about 50-60% weight that heavily accounts for composition weight.The compositions of this embodiment can contain suitable stain.Embodiment 58 in the table 1 has shown this embodiment.
The viscosity of hydration preparation may outbalance.Under the ideal situation, it should be enough low, so that pump is sprayed on the substrate to be wrapped with effective and efficient manner then equably to spraying in the unit continuously.Therefore, do the useful concentration of component in water and can be about 6% to about 15%, 6.5% to 11% more favourable, about 8% to about 11% be good (being percetage by weight).For guaranteeing the homogeneity of coated composition, desirable way is in the whole process that it is sprayed onto medicine or veterinary drug solid preparation, confectionery, seed, animal feed, fertilizer, parasite killing tablet or food, continues to stir its aqueous dispersions.
Among the present invention, edible preferably, can harden, the rapid release coated preparation generally can and use by simple program preparation.Following substances can be mixed and form dried coated composition: the dried dark compound of the coprocessing mixture of powders of microcrystalline Cellulose/chondrus ocellatus Holmes polysaccharide or microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide, reinforcement polymer (as hydroxyethyl-cellulose), Polyethylene Glycol or other suitable manufacturing methods, optional solid filler (as maltodextrin, lactose, mannitol or similar substance), antiseptic and/or surfactant.Edible stain, for example water-soluble dye or pigment can add before the hydration step of the final coated preparation of preparation.Next, above-mentioned dry mixture is slowly added in the pure water whirlpool of stirring.Stirring to mixture is long enough, so that all fully hydrations of all components.Obtain colored coating material if ask, then also will in the hydration coated composition, add water-soluble dye or pigment, preferably dispersion liquid or solution form.In this operational phase, also can randomly add surfactant and/or plasticizer.
In the preparation of microcrystalline Cellulose and ι chondrus ocellatus Holmes polysaccharide, the stirring that common propeller agitator provides just is enough to satisfy the requirement of fast hydrating.Hydration time may be as short as 0.5 hour.Its hydration time can be longer, and preferably longer, but it is believed that and there is no need to be longer than 3 hours.Hydration energy at room temperature takes place, also can take place under the temperature of (150) up to 65.5 ℃, under the temperature of about 48.9 ℃ (120) better.When preparation dispersion liquid under higher temperature, fully the required time of hydration shortens dramatically, and the viscosity of dispersion liquid also greatly reduces.But when at room temperature preparing the coating dispersion liquid, only need to prolong hydration time, reduce solids content a little, just can thoroughly reach satisfied effect.As previously mentioned, these preparations can be operated preparation the previous day (if talking about so more easily) at coating; But before coating, need to stir a period of time, to overcome the thixotropy that preparation produces in the process of storage of spending the night.Based on the coated preparation of cellulosic hydroxy alkyl ether (for example HPMC), the preparation based on crystallite and chondrus ocellatus Holmes polysaccharide of the present invention need not stir in the coating process incessantly unlike mainly, if but mixing effect is better, can continue to stir.
Any commercially available sprinkling coating machine can both be used for coating.The example of coating machine has preferably: the Accela-Cota coating machine that Vector High coating machine that VectorCorporation produces and Thomas Engineering produce.The personnel that are familiar with this technical field can the commanding apparatus parametric variable, comprise that inlet temperature, outlet temperature, air-flow, coating pan (coating pan) rotary speed and coated preparation pump into the speed of coating machine, produce refined coating thereby be provided on the basis of microcrystalline Cellulose and chondrus ocellatus Holmes polysaccharide material (coprocessing or do and mix).It is very important that import and outlet temperature are controlled at enough height, like this can the efficient drying coating, on giving identical tablet, damaged coating on new before another layer coating owing to roll in case go up the tablet of coating.
Hydroxyethyl-cellulose more can combine with water effectively than chondrus ocellatus Holmes polysaccharide.Therefore, the existence of main amount chondrus ocellatus Holmes polysaccharide has appreciable impact to the rate of drying of edible coating in the preparation of the present invention.Because the chondrus ocellatus Holmes polysaccharide that exists has been alleviated HEC to the adverse effect of drying time, shorten dramatically drying time.Like this, for eutectic active agents (for example ibuprofen), can reduce outlet temperature, and drying time is still shorter, this says it is very favourable from commercial angle.
The at high temperature easy especially stopped nozzles of hydroxyethyl-cellulose.Another benefit of preparation of the present invention is a stopped nozzles when having avoided at high temperature spraying dispersion liquid.
The coating amount of medicine or veterinary drug preparation between about 0.5% to about 4% better, between about 2% to about 3.5% better (all in not the weight of coated preparation).This contents level can provide refined, practical coating for many kinds of preparations.Wrapping thicker coating to tablet can be uneconomical, and may influence disintegrate ability or other character of tablet conversely.Coating is too thin can't to produce common desirable optimal properties again, for example, improves fragility or provides the suitable sense of taste to hide.
For confection, coating content should be between about 5% to about 10% (coming in the weight of coating confection not).The content of seed pelleting should be between about 3% to about 6% (coming in capsuled seed weight not).The coating of fertilizer and insecticide tablet and granule is 1% to about 3% more favourable (so that coated granule or tablet do not come).
Can see that from the following examples coating of the present invention can be successfully applied to the tablet that comprises many kinds of active component.For example, report the difficult coating of going up of Multivitamin tablet, because the vitamin surface is lipophilic.Similarly, ibuprofen also is the bad active component of going up coating.According to the present invention, comprise these difficult tablets of going up the active component of coating and all gone up at an easy rate coating, obtained the refined tablet of profile.In addition, coating of the present invention also is used to be carved with the tablet of letter or sign, and can letter or sign not linked up, and can cover even wipe the pattern that engraves like that.
Another purposes of coated preparation of the present invention is to substitute the tablet sugar-coat.Sugar-coat is mainly used to increase the weight and/or the size of tablet, but this is old technology, has many problems.Therefore, people wish to replace traditional sugar-coat with a kind of coating of being easier to use, just as shown in the embodiment 26.Another advantage of this coating program is not need to add as sugar-coat a top layer coating.
Under daily temperature and humidity, or under 40 ℃ and 75% relative humidity, coated tablet is stored 1 to 3 months, the result finds no the obvious degradation phenomenon and takes place.These disintegration of tablet required times are the same with tablet with a collection of firm first-class coating, and the dissolution rate of the tablet under the both of these case and time are with as the coating substrate but also there is not the tablet of coating basic identical.For the coating for preparing on the basis of chondrus ocellatus Holmes polysaccharide and microcrystalline Cellulose, this is a unexpected advantage, and is different with the known defect of the coating that is prepared by HPMC.
All components is typically pharmaceutically acceptable, edible food-grade material in the preparation.
(wherein percent is meant percetage by weight to the embodiment that provides below, tablet hardness is a unit with kip (Kp)) be preparation and using method for the coating that these are refined is described, they are not consumption and the type that is used for limiting this paper optional components, or limit the specific applying method of described tablet coating.
Embodiment 1
(coprocessed) microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30) of the coprocessing that adding 14.43 gram spray dryinges are crossed in the mixer of Patterson-Kelley bivalve, 18.36 gram polyvinyl pyrrolidone 29/32 (GAF), 16.40 gram Polyethylene Glycol 8000 (Union Carbide Corporation) and 0.2 gram 5# yellow food pigment.After fully mixing, slowly add in the 450 gram deionized waters that just in the 1L beaker, stirring with the Lightnin blender with doing component.After adding dried component, continue to stir 2 hours, make its abundant hydration.Filling 1 kilogram of aspirin tablet (500 milligrams of specifications) in Vector High coating machine LDCS, every average weight is 0.613 gram, shows 0.2% fragility after 4 minutes.Coating machine operation condition is, 100 ℃ of inlet temperatures, and 35 ℃ of outlet temperatures, rotating speed 22rpm, air is by 934.5 liters/minute of the speed (32 cubic feet/min) of spray coating machine.The coating solution for preparing previously sprayed 23 minutes with the pressure of 137.9kPa (20psi).Coated tablet weighs 0.6322 gram, shows that coating makes every tablet of tablet increase weight about 3.1%.The initial hardness of coated tablet is 7.35Kp (meansigma methodss of 10 tablets of tablets).The fragility of this coated tablet after 4 minutes is 0%, and the disintegration time in 37 ℃ deionized water is less than 3 minutes.Store one month under the room temperature, hardness is 6.55Kp, and disintegration time is less than 1 minute.Store two months under similarity condition, hardness is 6.99Kp.Store one month under 40 ℃ and 75% relative humidity, tablet hardness is 6.67Kp, and disintegration time is less than 5 minutes.Store two months under similarity condition, tablet hardness is 5.19Kp.
Embodiment 2
According to the method for embodiment 1, with coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30) that 19.05 gram spray dryinges are crossed, 0.25 gram hydroxyethyl-cellulose (Aqualon 250L, HerculesIncorporated), 10.40 gram Polyethylene Glycol 8000 and 0.30 gram 5# yellow food pigment are made dry mixture, add in the 410 gram deionized waters that just stirring with the Lightnin blender in the 1L beaker.Stir made the abundant hydration of component in 1 hour after, the viscosity solution that obtains is sprayed onto on 1 kilogram of aspirin tablet (500 milligrams of specifications) with Vector High coating machine LDCS.Used condition comprises: inlet temperature 80-85 ℃, and outlet temperature 36-41 ℃, rotating speed 22rpm, air is by 1189.3 liters/minute of the speed (42 cubic feet/min) of spray coating machine.Finish after being sprayed at 25 minutes.The original depth of these coated tablets is 6.0 millimeters (0.245 inches), and hardness is 7.15Kp.The fragility of tablet after 4 minutes is 0%, without any cracked or fracture.Disintegration time in 37 ℃ of pure water is less than 2 minutes.
Embodiment 3
According to the method for embodiment 1, with coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30) that 19.05 gram spray dryinges are crossed, 0.25 gram hydroxyethyl-cellulose (Aqualon 250L, HerculesIncorporated), 5.40 gram Polyethylene Glycol, 8000,5.0 gram Micro Talc and the red food colour of 0.30 gram 40# are made dry mixture, add in the 400 gram deionized waters that just stirring with the Lightnin blender in the 1L beaker.Stir made the abundant hydration of component in 3 hours after, the viscosity solution that obtains is sprayed onto on 1 kilogram of aspirin tablet (500 milligrams of specifications) with Vector High coating machine LDCS, the average weight of every tablet of tablet be 0.613 the gram.Used condition comprises: inlet temperature 77-81 ℃, and outlet temperature 39-45 ℃, rotating speed 23rpm, air is by 1047.7 liters/minute of the speed (37 cubic feet/min) of spray coating machine.Finish after being sprayed at 40 minutes.The average weight of these coated tablets is 0.6334 gram, shows that coating makes every tablet weightening finish 3.3%.The original depth of these coated tablets is 6.0 millimeters (0.245 inches), and hardness is 8.55Kp.Disintegration time in 37 ℃ of pure water is less than 3 minutes.Store one month under the room temperature, hardness is 7.61Kp, and disintegration time is less than 5 minutes.Store two months under similarity condition, tablet hardness is 7.99Kp.Store one month under 40 ℃ and 75% relative humidity, tablet hardness is 7.64Kp, and disintegration time is less than 1 minute.Store two months under similarity condition, tablet hardness is 7.34Kp.
Embodiment 4
According to the method for embodiment 1, with coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30) that 19.05 gram spray dryinges are crossed, 0.25 gram hydroxyethyl-cellulose (Aqualon 250L, HerculesIncorporated), 10.40 gram Polyethylene Glycol 8000 and the yellow food colour of 0.30 gram 5# are made dry mixture, add in the 400 gram deionized waters that just stirring with the Lightnin blender in the 1L beaker.Stir made the abundant hydration of component in 1.5 hours after, the viscosity solution that obtains is sprayed onto on 1 kilogram of Genpril (200 milligrams of specifications) with Vector High coating machine LDCS, every tablet of tablet weighs 0.3114 gram.Used condition comprises: inlet temperature 73-78 ℃, and outlet temperature 30-34 ℃, rotating speed 19-22rpm, air is by 1104.3 liters/minute of the speed (39 cubic feet/min) of spray coating machine.Finish after being sprayed at 27 minutes.The disintegration time of uncoated tablets in 37 ℃ of pure water is less than 15 seconds.The fragility of uncoated tablets is 0.0667%.Behind the coating, the tablet average weight is 0.3214 gram, shows weightening finish 3.2%.The thickness of these coated tablets is 5.99 millimeters (0.236 inches), and hardness is 11.47Kp.The fragility of these tablets after 4 minutes is 0%.Store one month under the room temperature, hardness is 8.55Kp.Store one month under 40 ℃ and 75% relative humidity, tablet hardness is 8.28Kp.Under two set conditions, the disintegration time of tablet all is less than 2 minutes.Store two months under similarity condition, hardness is 6.99Kp.Store two months under 40 ℃ and 75% relative humidity, hardness is 13.25Kp.Store two months under two set conditions, the disintegration of tablet time of record is 30-60 second.
Embodiment 5
According to the method for embodiment 1, with coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30) that 19.05 gram spray dryinges are crossed, 0.25 gram hydroxyethyl-cellulose (Aqualon 250L, HerculesIncorporated), 10.40 gram Polyethylene Glycol yellow food colours of 8000,0.10 gram 5# and the red food colour of 0.10 gram 40# are made dry mixture, add in the 400 gram deionized waters that just stirring with the Lightnin blender in the 1L beaker.Stir when enough after the abundant hydration of chien shih component, the viscosity solution that obtains is sprayed onto on 1 kilogram of nuclear core of being made up of the calcium carbonate of 20% microcrystalline Cellulose and 80% with Vector High coating machine LDCS, each nuclear core on average weighs 1.05 grams.Used condition comprises: inlet temperature 73-80 ℃, and outlet temperature 36-39 ℃, rotating speed 19rpm, air is by 1104.3 liters/minute of the speed (39 cubic feet/min) of spray coating machine.Finish after being sprayed at 45 minutes.The average weight of every coating tablets tablet is 1.07 grams, shows weightening finish 1.9%.The thickness of these tablets is 5.56 millimeters (0.219 inches), and hardness is 23.08Kp.The fragility of this coated tablet after 4 minutes is 0%, without any cracked or fracture.Disintegration time in 37 ℃ of pure water is less than 3 minutes.
Embodiment 6
According to the method for embodiment 1, the dry mixture of 19.05 coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharides (70: 30) of crossing of gram spray dryinges, 10.65 gram Polyethylene Glycol 8000 and the yellow food colour of 0.30 gram 5# is just added in the 1L beaker with 400 restraining in the deionized waters that the Lightnin blender is stirring.After the stirring certain hour makes the abundant hydration of component, the viscosity solution that obtains is continued to stir, with Vector High coating machine LDCS it is sprayed onto on 1 kilogram of nuclear core of being made up of microcrystalline Cellulose and calcium carbonate simultaneously, it is the same that this nuclear core is used for the nuclear core of coating with embodiment 5.Used condition comprises: inlet temperature 78-79 ℃, and outlet temperature 38-45 ℃, rotating speed 21-22rpm, air is by 1076.0 liters/minute of the speed (38 cubic feet/min) of spray coating machine.Finish after being sprayed at 40 minutes.The fragility of tablet after 12 minutes is 0%, without any cracked or fracture.Disintegration time in 37 ℃ of pure water is less than 3 minutes.The coating that this coating does not contain hydroxyethyl-cellulose is good-looking.
Embodiment 7
According to the method for embodiment 1, coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30), 0.55 gram hydroxyethyl-cellulose 250L, 11.40 dry mixtures that restrain Polyethylene Glycol 8000 and 0.20 gram yellow iron oxide that 20.95 gram spray dryinges are crossed add in the 450 gram deionized waters that just stirring with the Lightnin blender in the 1L beaker.Stir made the abundant hydration of component in 1.5 hours after, the viscosity solution that obtains is continued to stir, simultaneously it is sprayed onto 1.03 kilograms of compacting microcrystalline Cellulose that are carved with the FMC sign with Vector High coating machine LDCS and examines core (Avicel PH-200) on, each nuclear core on average weighs 0.267 gram.Used condition comprises: inlet temperature 87-90 ℃, and outlet temperature 35-39 ℃, rotating speed 17rpm, air is by 1076.0 liters/minute of the speed (38 cubic feet/min) of spray coating machine.Finish after being sprayed at 27 minutes.The average weight of coating nuclear core is 0.2752 gram, has shown the coating of 3.07% (weight).The disintegration time of coating nuclear core is not less than 30 seconds, and the disintegration time of coating nuclear core is less than 2 minutes.The fragility after 4 minutes of coating nuclear core and coating nuclear core is not 0%, without any cracked or fracture.The average thickness of coating nuclear core is not 4.572 millimeters (0.180 inches), and the average thickness of coating nuclear core is increased to 4.594 millimeters (0.181 inches).The average hardness of coating nuclear core is not 9.14Kp, and the average hardness of coated tablet is 10.35Kp.
Embodiment 8
According to the method for embodiment 1, with coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (90: 10) that 285.75 gram spray dryinges are crossed, 7.5 gram hydroxyethyl-cellulose 250L, 156.0 gram Polyethylene Glycol 8000 and the hydrophilic iron oxide red of 45.0 grams are made dry mixture.Getting this dried dark compound of a part (60 gram) adds in the 540 gram deionized waters that just stirring with the Lightnin blender in the 1L beaker.Stir when sufficiently long after the abundant hydration of chien shih component, the viscosity solution that obtains is continued to stir, simultaneously it is sprayed onto the 2Kg acetaminophen with Vector High coating machine LDCS and examines on the core.Used condition comprises: inlet temperature 73-85 ℃, and outlet temperature 40-43 ℃, rotating speed 13rpm, air is by 1217.6 liters/minute of the speed (43 cubic feet/min) of spray coating machine.Finish after being sprayed at 30 minutes.The outward appearance of gained coated tablet is not so good as among the embodiment 1 to 7 with 70: 30 the microcrystalline Cellulose and the coated tablet of ι chondrus ocellatus Holmes polysaccharide combined preparation.The fragility test of these coated tablets is satisfactory, but observes slight cracked and corrosion.
Embodiment 9
Method according to embodiment 1, restrain coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30) that spray dryinges are crossed with 190.8,5.02 gram hydroxyethyl-cellulose 250L, 104.2 gram Polyethylene Glycol 8000,1.5 gram methyl hydroxybenzoate, 0.15 the gram propylparaben, 18.48 gram maltodextrin M-180,4.95 gram Tween 80s and 9.90 gram Chroma Kote Red #40 make dry mixture.Add in the 4451 gram deionized waters that just in the 1L beaker, stirring all doing dark compound with the Lightnin blender.Stir when sufficiently long after the abundant hydration of chien shih component, the viscosity solution that obtains is continued to stir, with Accela Cota coating machine it is sprayed onto the Avicel that 11Kg contains 200 milligrams of chlorphenamines simultaneously On the PH-200 nuclear core.Used condition comprises: inlet temperature 83-87 ℃, and 40 ℃ of outlet temperatures, the chassis rotating speed 11-12rpm of 60.96 centimetres (24 inches).Finish after being sprayed at 71 minutes.The average hardness of the tablet before the coating is 3.1Kp, and the average hardness of coated tablet is 3.9Kp, and the fragility after 4 minutes is 0%.Coated tablet disintegrate required time in 37 ℃ of pure water is less than 1 minute.
Embodiment 10
Method according to embodiment 1, restrain coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30) that spray dryinges are crossed with 194.7,5.61 gram hydroxyethyl-cellulose 250L, 106.4 gram Polyethylene Glycol 8000,1.65 gram methyl hydroxybenzoate, 0.165 the gram propylparaben, 18.48 gram maltodextrin M-180,4.95 gram Tween 80s and the red 40# of 16.5 gram Chroma Kote make dry mixture.Add in the 4384 gram deionized waters that just in the 1L beaker, stirring all doing dark compound with the Lightnin blender.Stir when sufficiently long after the abundant hydration of chien shih component, the viscosity solution that obtains is continued to stir, with Accela Cota coating machine it is sprayed onto on the 10Kg Multivitamin capsule sheet (caplet) simultaneously.Used condition comprises: inlet temperature 75-78 ℃, and outlet temperature 36-37 ℃, the chassis rotating speed 10rpm of 60.96 centimetres (24 inches).Finish after being sprayed at 95 minutes.The average weight of coating capsule sheet is not 1.2503 grams, and the average weight of coating capsule sheet is 1.281 grams, has shown the coating of 2.46% (weight).The hardness of coating capsule sheet is not 19.67Kp, and the hardness of coating capsule sheet is increased to 25.14Kp.The fragility of coating capsule sheet after 4 minutes is 0%.
Embodiment 11
Method according to embodiment 1, restrain coprocessing microcrystalline Cellulose/ι chondrus ocellatus Holmes polysaccharide (70: 30) that spray dryinges are crossed with 68.94,1.82 gram hydroxyethyl-cellulose 250L, 37.63 gram Polyethylene Glycol 8000,0.545 gram methyl hydroxybenzoate, 0.0545 the gram propylparaben, 10.24 gram maltodextrin M-180,1.79 gram Tween 80s are made dry mixture.Do not add stain in this preparation.Add with 1068 restraining in the deionized waters that the Lightnin blender stirs all doing dark compound.Stir when sufficiently long after the abundant hydration of chien shih component, the viscosity solution that obtains is continued to stir, with Accela Cota coating machine it is sprayed onto the circle that 11Kg contains 500 milligrams of aspirin simultaneously and examines on the core.Used condition comprises: inlet temperature 74-80 ℃, and 40 ℃ of outlet temperatures, the chassis rotating speed 9-11rpm of 60.96 centimetres (24 inches).Finish after being sprayed at 50 minutes.When on the coating of nuclear on the core time 0.5% (weight), suspend and spray, the sample that takes out heavy 1.4Kg is used for test, recovers to spray the level of coating to 1.0% (weight) on the remaining nuclear core then.The hardness of coating nuclear core is not 8.25Kp, and the coating amount is that the hardness of the nuclear core of 0.5% (weight) reduces to 7.5Kp, and the coating amount is that the hardness of the nuclear core of 1% (weight) is 7.87Kp.The disintegrate required time of the nuclear core of two kinds of coating amounts all is less than 1 minute.The fragility of nuclear core after 4 minutes before the coating is greater than 6%, and the coating amount is that the fragility of the nuclear core of 0.5% (weight) slightly reduces to 1%, and the coating amount is that the fragility of the nuclear core of 1% (weight) further is reduced to 0.1%.
Embodiment 12
In the mixer of Patterson-Kelley bivalve, add 229.5 grams by microcrystalline Cellulose (Avicel PH-105,160.65 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (68.85 gram), 49.5 restrain hydroxyethyl-cellulose (Aqualon 250L), 148.5 gram Polyethylene Glycol 8000 (Union Carbide Corporation) and 9.0 gram 5# toner yellows (yellow lake).After fully mixing, slowly add in the 4550 gram deionized water whirlpools that just stirring with the Lightnin blender in large beaker doing component, water has been heated to 54.4 ℃ (130 °F).After adding dried component, continue to stir 2 hours, make its abundant hydration.During the hydration, the temperature of dispersion liquid is reduced to 33.3 ℃ (92 °F).5 kilograms of aspirin tablets of filling in Accela Cota coating machine (500 milligrams of specifications, every average weight is 0.613 gram, shows 0.2% fragility after 4 minutes) and 5 kilograms of Genprils (every heavy 0.3114 gram).Coating machine operation condition is: inlet temperature 100-108.9 ℃, and outlet temperature 40-45 ℃, rotating speed 10-12rpm.In required 53 minutes sprinkling process, gone up the coating of 3% (weight is in tablet weight).After having sprayed, before from the coating machine, taking out, allow the dry again 3-5 branch of coated tablet clock time.This tablet coating has good surface appearance.From every kind of tablet, take out 10 and carry out the fragility test.There are not vestiges cracked or wearing and tearing after 8 minutes.
Embodiment 13
According to the method for embodiment 12, restrain by microcrystalline Cellulose (Avicel 238.5 PH-105,166.95 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (71.55 gram), 40.5 restrain hydroxyethyl-cellulose (Aqualon 250L), 148.5 gram Polyethylene Glycol 8000 (Union Carbide Corporation), 13.5 gram maltodextrin (Maltrin M-180) and 9.0 gram 5# toner yellows are made dry mixture, are dispersed in 4550 grams and have been heated in the deionized water of 45.6 ℃ (114).Hydration needs 1 hour.3.33 kilograms of aspirin tablet (500 milligrams of specifications of filling in Accela Cota coating machine, every average weight is 0.613 gram, shows 0.2% fragility after 4 minutes), 3.33 kilograms of acetaminophen capsule sheets and 3.33 kilograms of Genprils (every heavy 0.3114 gram).Coating machine operation condition is: inlet temperature 102.8-110.6 ℃, and outlet temperature 41-47 ℃, rotating speed 10-12rpm.In required 51 minutes sprinkling process, gone up the coating of 3% (weight is in tablet weight).After having sprayed, before from the coating machine, taking out, allow the dry again 5 fens clock times of coated tablet.This tablet coating has good surface appearance.To 10 minutes fragility test shows that coating aspirin and acetaminophen tablet (10 every kind) carry out, do not occur cracked and damage.The disintegration time of coating aspirin, acetaminophen and Genpril was respectively 80 seconds, 295 seconds and 26-27 minute.But the disintegration time of coating ibuprofen nuclear core is about 25 minutes.In 900 milliliters of 0.05M phosphate buffers, carry out 30 minutes stripping experiment with the rotating speed of 50rpm with USP instrument 2 (oar formula (paddle)), the result shows, at pH is that 5.8: 100 ± 0.8% acetaminophen can discharge, and is that 7.2: 97 ± 2.2% ibuprofen can discharge at pH.Carry out the stripping experiment with USP instrument 1 (basket (basket)) with the rotating speed of 50rpm in 500 milliliters of 0.05M acetate buffers, the result shows, pH is that 4.5: 93 ± 6.9% aspirin can discharge.
Embodiment 14
According to the method for embodiment 12, restrain by microcrystalline Cellulose (Avicel 238.5 PH-105,166.95 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (71.55 gram), 40.5 restrain hydroxyethyl-cellulose (Aqualon 250L), 148.5 gram Polyethylene Glycol 8000 (Union Carbide Corporation) and 22.5 gram maltodextrins (Maltrin M-180) are made dry mixture, are dispersed in 4550 and restrain in the deionized water that has been heated to 90 ℃.Hydration needs 75 minutes.12 kilograms of nuclear cores that comprise 20% microcrystalline Cellulose and 80% calcium carbonate of filling in Accela Cota coating machine, each nuclear core on average weighs 1.05 grams.Coating machine operation condition is: inlet temperature 92.8-108.3 ℃, and outlet temperature 42-46 ℃, rotating speed 11rpm.In required 76 minutes sprinkling process, gone up the coating of 3% (weight is in tablet weight).After having sprayed, before from the coating machine, taking out, allow the dry again 4 fens clock times of coated tablet.This tablet coating has good surface appearance.
Embodiment 15
In the mixer of Patterson-Kelley bivalve, add 234.0 grams by microcrystalline Cellulose (Avicel PH-105,166.5 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (67.5 gram), 67.5 restrain hydroxyethyl-cellulose (Aqualon 250L), 63.0 gram maltodextrin (Maltrin M-180, Grain ProcessingCorporation), 63.0 gram titanium dioxide and 22.5 gram Red#40 aluminum color lakes.After fully mixing, slowly add in the 4550 gram deionized water at room temperature whirlpools that just in large beaker, stirring with the Lightnin blender with doing component.Stirring lasts till till the abundant hydration of component.The acetaminophen capsule sheet of 2 kilograms of equivalent of filling, ibuprofen capsule sheet and Multivitamin nuclear core in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 102-109 ℃, and outlet temperature 40-42 ℃, rotating speed 10rpm.In required 55 minutes sprinkling process, gone up the coating of 3% (weight is in tablet weight).After having sprayed, before from the coating machine, taking out, allow the dry again 3-5 branch of coated tablet clock time.Coated tablet has good distribution of color.From every type tablet, get 10 and carry out fragility mensuration.There are not vestiges cracked or wearing and tearing after 8 minutes.
Embodiment 16
In the mixer of Patterson-Kelley bivalve, add 76.5 grams by microcrystalline Cellulose (Avicel PH-105,55.5 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (21.0 gram), 22.5 restrain hydroxyethyl-cellulose (Aqualon 250L), 28.5 gram maltodextrin (Maltrin M-180, Grain ProcessingCorporation), 10.0 gram Red#40 aluminum color lakes and 0.7 gram sodium lauryl sulphate.After fully mixing, slowly add in the 1399.4 gram deionized water at room temperature whirlpools that just in large beaker, stirring with the Lightnin blender with doing component.Stirring lasts till till the abundant hydration of component.Filling 2 kilograms of acetaminophen capsule sheets (500 milligrams of specifications) in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 57-70 ℃, and outlet temperature 35-40 ℃, rotating speed 9-10rpm.In required 56 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).It is believed that coating is gratifying, can not cause linking in the sign, have clear, good surface appearance.
Embodiment 17
In the mixer of Patterson-Kelley bivalve, add 76.5 grams by microcrystalline Cellulose (Avicel PH-105,55.5 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (21.0 gram), 22.5 restrain hydroxyethyl-cellulose (Aqualon 250L), 28.5 gram maltodextrin (Maltrin M-180, Grain ProcessingCorporation), 10.0 gram red dye mixtures (Warner Jenkinson) and 5.0 gram lubricants (Eastman EL).After fully mixing, will do component and slowly add in the 1441.0 gram deionized waters, and with Silverson mixer disperses 10-15 minute.Under the room temperature, in large beaker, use the Lightnin blender with dispersion liquid hydration while stirring 1.5 hours.Filling 2 kilograms of acetaminophen capsule sheets (500 milligrams of specifications) in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 73-85 ℃, and outlet temperature 38-44 ℃, rotating speed 10-11rpm.In required 60 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).Coating has obvious gloss, can not cause linking in the sign, covers fully.
Embodiment 18
In a big Patterson-Kelley bivalve mixer, add 1.940 kilograms by microcrystalline Cellulose (Avicel PH-105,1.358 kilograms) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (0.582 kilogram), 0.436 kilogram of hydroxyethyl-cellulose (Aqualon 250L), 0.277 kilogram of maltodextrin (Maltrin M-180, Grain Processing Corporation) and 1.307 kilograms of Polyethylene Glycol 8000 (UnionCarbide Corporation).After fully mixing, dried component is slowly added in 40.04 kilograms of distilled water that stir in groove.Under the room temperature, serosity was the middle hydration that continues to stir 2 hours.Stop to stir, coated preparation was left standstill 8 hours; Stirred then 1 hour, and began the coating operation again.Filling 120 kilograms of acetaminophen capsule sheets (comprising 500 milligrams of activating agents/capsule sheet) in being furnished with 1.22 meters (48 inches) Accela-Cota coating machines of 4 mixing baffles.Coating machine operation condition is: inlet temperature 62-71 ℃, and outlet temperature 42-44 ℃, rotating speed 4-4.5rpm.Carrying the speed of coated preparation toward the coating machine is 400 ml/min.In required 107 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).Coating has good surface appearance.
Acetaminophen from coating capsule sheet dissolved speed with the flat oar of USP instrument 2[(paddle)] measure in 900 milliliters, pH are 5.8 0.05M phosphate buffer with the rotating speed of 50rpm.After 10 minutes, 20 minutes and 30 minutes, measure the acetaminophen of stripping respectively.Stripping is after about 79%, 20 minute after about 97%, 30 minute about 100% after 10 minutes.With these coated tablets 24 weeks of storage (available desiccant, also can without desiccant) under 40 ℃, 75% relative humidity, above-mentioned dissolution rate is constant substantially.
Embodiment 19
In the mixer of Patterson-Kelley bivalve, add 72.8 grams by microcrystalline Cellulose (Avicel PH-105,56.25 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (16.55 gram), 33.08 restrain hydroxyethyl-cellulose (Aqualon 250L) with the hydrophilic iron oxide red of 44.15 grams.After fully mixing, will do component and add in the 1516.7 gram deionized waters, stir 2.5 hours under the room temperature, make the abundant hydration of compositions.Filling 2 kilograms of acetaminophen capsule sheets (500 milligrams of specifications) in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 81-95 ℃, and outlet temperature 38-46 ℃, rotating speed 10rpm.In required 45 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).Coated tablet does not show fragility after 8 minutes.Tablet disintegrate in 37 ℃ of immobilized water needs 3-4 branch clock time.
Embodiment 20
In the mixer of Patterson-Kelley bivalve, add 73.5 grams by microcrystalline Cellulose (Avicel PH-105,55.5 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (18.0 gram), 33.0 restrain hydroxyethyl-cellulose (Aqualon 250L), 15.0 gram maltodextrin (Maltrin M-180, Grain ProcessingCorporation) and the hydrophilic oxidation Huang of 22.5 grams.After fully mixing, will do component and add in the 1516.7 gram deionized waters, and at room temperature stir nearly 5 hours, so that the abundant hydration of compositions.Filling 2 kilograms of acetaminophen capsule sheets (500 milligrams of specifications) in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 74-83 ℃, and outlet temperature 35-39 ℃, rotating speed 10-12rpm.In required 51 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).The color homogeneity is good.
Embodiment 21
In the mixer of Patterson-Kelley bivalve, add 73.5 grams by microcrystalline Cellulose (Avicel PH-105,55.5 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (18.0 gram), 33.0 restrain hydroxyethyl-cellulose (Aqualon 250L) with 21.0 gram maltodextrin (Maltrin M-180, Grain ProcessingCorporation).Simultaneously, in 1516.7 gram deionized waters, add 22.5 gram titanium dioxide, stirred 5 minutes with the Silverson blender.After dried component is fully mixed, it is slowly added in the whirlpool of titanium oxide dispersion, at room temperature stirred 2.25 hours, so that the abundant hydration of compositions with the Lightnin blender.The plain capsule sheet of 2 kilograms of yellow multifilaments of filling (on average weighing 1.258 grams) in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 85-91 ℃, and outlet temperature 38-39 ℃, rotating speed 11rpm.In required 51 minutes sprinkling process, gone up the coating of 3.5% (weight is in capsule sheet weight).Through 10 minutes fragility test, coated tablet did not occur cracked or fracture.Yellow thoroughly deepening.
Embodiment 22
In the mixer of Patterson-Kelley bivalve, add 73.5 grams by microcrystalline Cellulose (Avicel PH-105,55.5 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (18.0 gram), 33.0 restrain hydroxyethyl-cellulose (Aqualon 250L) with 21.0 gram maltodextrin (Maltrin M-180, Grain ProcessingCorporation).Simultaneously, in 1516.7 gram deionized waters, add 31.5 gram titanium dioxide, stirred 5 minutes with the Silverson blender.After dried component is fully mixed, it is slowly added in the whirlpool of titanium oxide dispersion, at room temperature stirred 1 hour, so that the abundant hydration of compositions with the Lightnin blender.2 kilograms of acetaminophen capsule sheets of having used the iron oxide red coating of filling in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 76-86 ℃, and outlet temperature 33-38 ℃, rotating speed 13rpm.In required 56 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).Through 10 minutes fragility test, coated tablet did not occur cracked or fracture.The red thoroughly deepening of capsule sheet.
Embodiment 23
In the mixer of Patterson-Kelley bivalve, add 78.0 grams by microcrystalline Cellulose (Avicel PH-105,55.5 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (22.5 gram), 33.0 restrain hydroxyethyl-cellulose (Aqualon 250L) with 9.0 gram maltodextrin (Maltrin M-180, Grain ProcessingCorporation).Simultaneously, in 1516.7 gram deionized waters, add 30.0 gram titanium dioxide, stirred 5 minutes with the Silverson blender.After dried component is fully mixed, it is slowly added in the whirlpool of titanium oxide dispersion, at room temperature stirred 1 hour, so that the abundant hydration of compositions with the Lightnin blender.2 kilograms of chlorphenamine tablets of filling in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 76-86 ℃, and outlet temperature 36-39 ℃, rotating speed 12-15rpm.In required 59 minutes sprinkling process, gone up the coating of 3% (weight is in tablet weight).Coating covers good, the tablet colour-darkening.
Embodiment 24
In the mixer of Patterson-Kelley bivalve, add 71.33 grams by microcrystalline Cellulose (Avicel PH-105,49.94 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (21.39 gram), 16.01 restrain hydroxyethyl-cellulose (Aqualon 250L), 48.05 gram Polyethylene Glycol 8000 (Union Carbide Corporation), 10.19 gram maltodextrin (Maltrin M-180, Grain Processing Corporation) and 4.5 gram Muscovitums (White Timeron MP-10, E.M.Merck and Company).After dried component is fully mixed, it is slowly added in the 1516.7 gram deionized waters, at room temperature stir the enough time, so that the abundant hydration of compositions with the Lightnin blender.2 kilograms of acetaminophen capsule sheets of filling in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 73-80 ℃, and outlet temperature 35-39 ℃, rotating speed 8-16rpm.In required 57 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).Coated tablet has good surface appearance, is creamy white.
Embodiment 25
In the mixer of Patterson-Kelley bivalve, add 78.0 grams by microcrystalline Cellulose (Avicel PH-105,55.5 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (22.5 gram), 33.0 restrain hydroxyethyl-cellulose (Aqualon 250L) with 1.5 gram stearic acid.Simultaneously, in 1516.7 gram deionized waters, add 37.5 gram titanium dioxide, stirred 5 minutes with the Silverson blender.After dried component is fully mixed, it is slowly added in the whirlpool of titanium oxide dispersion, at room temperature stir the sufficiently long time, so that the abundant hydration of compositions with the Lightnin blender.2 kilograms of chlorphenamine capsule sheets of filling in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 74-80 ℃, and outlet temperature 33-37 ℃, rotating speed 13-16rpm.In required 54 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).This preparation is good to capsule sheet parcel, and makes coating capsule sheet have good-looking gloss.
Embodiment 26
In the mixer of Patterson-Kelley bivalve, add 300 grams by microcrystalline Cellulose (Avicel PH-105,200 grams) and the mixture and 100 formed of ι chondrus ocellatus Holmes polysaccharide (100 gram) restrain Polyethylene Glycol 8000 (UnionCarbide Corporation).After dried component is fully mixed, it is slowly added in the whirlpool of 5314.3 gram deionized waters, at room temperature stirred 2.25 hours, so that the abundant hydration of compositions with the Lightnin blender.This dispersion liquid smooth in appearance, not protuberance.2 kilograms of placebo of filling in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 77-98 ℃, and outlet temperature 32-35 ℃, rotating speed 12-18rpm.In required 187 minutes sprinkling process, gone up the coating of 15% (weight is in tablet weight).The gained coated tablet is gone up coating once more with same preparation, and coating machine operation condition is: inlet temperature 88-98 ℃, and outlet temperature 40-43 ℃, chassis rotating speed 18-19rpm.The tablet weightening finish 32% that finally obtains.This coating might substitute traditional sugar-coat.
Embodiment 27
In the mixer of Patterson-Kelley bivalve, add 49.0 grams by microcrystalline Cellulose (Avicel PH-105,34.3 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (14.7 gram), 11.0 restrain hydroxyethyl-cellulose (Aqualon 250L), 33.0 gram Polyethylene Glycol 8000 (Union Carbide Corporation), 7.0 gram maltodextrin (Maltrin M-180, Grain Processing Corporation) and 1.0 gram orchil #40 (Allied Chemical).After dried component is fully mixed, it is slowly added in the whirlpool of 1021.3 gram deionized waters, at room temperature stirred 2 hours, so that the abundant hydration of compositions with the Lightnin blender.2.0 kilograms of yellow multidimensional of filling are given birth to the capsule sheet in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 65-79 ℃, and outlet temperature 37-41 ℃, rotating speed 10-11rpm.After sprinkling is finished, allow coating capsule sheet in the coating machine, stop 1 minute more, make coating obtain intensive drying.In required 92 minutes sprinkling process, gone up the coating of 3% (weight is in capsule sheet weight).Coating capsule sheet distribution of color is good, and makes the original yellow deepening of capsule sheet, also can not transfer on the skin when scraping with finger.
Embodiment 28
Dry preparation sample 90 grams of preparation among the embodiment 18 are dissolved in 910 ml deionized water, and 2 liters of glass beakers adorning this deionized water partly are immersed in 85 ℃ of thermal cycle water-baths.Dried powder is added in the water whirlpool that the rotating speed with 1550rpm stirs.Joining day requires to about 1 minute.Under 85 ℃ temperature, stirred lasting 60 minutes.During end, take out 10 milliliters of these slurry samples, mix with 90 milliliters of sterile deionized waters.Then dilute sample is cultivated on board-like counting agar casting plate making full bacteria-measuring, measured containing to cultivate on the Rhizoma Solani tuber osi agar glucose casting plate of chlortetracycline to do full yeast and mycete.Before counting, culture plate was cultivated 5 days at 25 ℃.After 48 hours, measure for two kinds and find that colony-forming units is less than 10 in every gram serosity.In order to compare, except the temperature of the used water of dispersion of dry preparation changes into 19.5 ℃, using the same method has prepared a identical serosity.After 25 ℃ of cultivations, carry out sample determination, observe nearly 9,000 bacterial clumps formation units after 24 hours, observe after 36 hours and reach 1,300 yeast and mold colony formation unit.This experiment shows, as long as serosity prepares being not less than under 85 ℃ the aseptic condition, the aqueous slurry that obtains just can keep stable in a long time.
Embodiment 29
In the mixer of Patterson-Kelley bivalve, add 43.0 grams by microcrystalline Cellulose (Avicel PH-105,33 grams) and the mixture formed of ι chondrus ocellatus Holmes polysaccharide (10 gram), 20 restrain hydroxyethyl-cellulose (Aqualon 250L), 23 gram glycerol triacetates, 4.0 gram propylene glycol alginates and 3 gram Pluronic F-68 (BASF).After dried component is fully mixed, mixture is slowly added in the 1011.1 gram deionized water whirlpools that stir with the Lightnin blender.This dispersion liquid at room temperature stirs 1.5 hours, so that the abundant hydration of compositions.In this dispersion liquid, add red #40 dispersion liquid (the Crompton ﹠amp of 7 grams; Knowles).The viscosity of this dispersion liquid is fit to spraying.1 kilogram of acetaminophen tablet of filling and ibuprofen capsule sheet in Vector High coating machine LDCS.Coating machine operation condition is: inlet temperature 82-87 ℃, and outlet temperature 37-42 ℃, rotating speed 13-15rpm.In required 50 minutes sprinkling process, gone up the coating of 3% (weight is in tablet and capsule sheet weight).The fragility of tablet and capsule sheet is 0% after 10 minutes.The coating that obtains has good outward appearance.
Embodiment 30
According to the method for embodiment 18, mix a kind of coated composition of preparation by doing, its prescription is as follows:
Constituent content
Microcrystalline Cellulose (Avicel PH-105) 37.5
ι chondrus ocellatus Holmes polysaccharide 14.7
Polyethylene Glycol 8,000 34
Hydroxyethyl-cellulose 250L 11
Maltodextrin M-180 3
This preparation is dispersed in the water, and in 49 minutes time, dispersion liquid is sprayed on 2.0 kilograms of acetaminophen capsule sheets, inlet temperature 68-72 ℃, outlet temperature 34-36 ℃, rotating speed 9-12rpm.After 10 minutes, be surrounded by the coating of 3% (weight) on the capsule sheet.
Acetaminophen dissolution rate from coating capsule sheet is measured in pH is 900 milliliters of 0.05M phosphate buffers of 5.8 with the rotating speed of 50rpm with USP instrument 2 (flat oar (paddle)).After 10 minutes, 20 minutes and 30 minutes, measure the acetaminophen of stripping respectively.
To prepared coated tablet, measured coating and be bonded in degree on the capsule sheet.Used " peeling off experiment " adopts single-column TA-XT2 type to stablize micro-system textile analysis instrument, controls and analyzes with microcomputer.This instrument is fixing by two HDP/TCAP type platens (platen), and the two front all is two-sided foaming thing.The capsule sheet is placed in the foamy centre that is arranged in following platen space.Platen above reducing makes it the capsule sheet is produced 800 power that restrain.This power was kept for 10 seconds, remove out top platen with the speed of 10 mm/second then.Data sampling speed was 500 point/seconds.Making film separate required maximum, force from tablet and be defined as " tablet coating bonding force ", is unit with the gram.
The experiment of coating tension force is finished with Instro 5564 type list bundle testers, this instrument computer (being furnished with IX groupware bag) control and analysis.Experiment parameter comprises: 40 millimeters of measuring lengths, crosshead speed 2 mm/min.Coating membrane carries out casting and drying at 45 ℃.Preparation size is 70 millimeters * 12 millimeters, the sample film of thickness between 0.2 millimeter-0.5 millimeter, and is that 22 ℃, relative humidity are to deposit 3 days in 34% the environment in temperature, carries out balance test then.Maximum elongation percentage ratio, maximum stress and Young's modulus are measured.
Under the results are summarized in of these tests:
Stripping quantity (%) %
After 10 minutes 77
After 20 minutes 96
After 30 minutes 98
Coating bonding force (gram) 942
Maximum elongation amount (%) 3.34
Maximum stress (milli handkerchief) a20.3
Young's modulus (milli handkerchief) 1249
aMilli Pascal
Embodiment 31-33
According to the method for embodiment 19, the component of embodiment 31,32,33 is done separately and is mixed, and obtains preparation as shown in the table:
Embodiment 31 32 33
Weight (gram)
Avicel PH-105 38 34.3 34.3
Chondrus ocellatus Holmes polysaccharide 11 14.7 14.7
Hydroxyethyl-cellulose-11 11
PGA a 7
PEG b 34 33 33
Lecithin c747
Maltrin M-180 3 3
A propylene glycol alginate (Protonal Ester SD-LB, Pronova)
B Polyethylene Glycol 8000
C hydroxylation soybean lecithin
Then above-mentioned preparation is dispersed in the deionized water, the dispersion liquid that obtains is sprayed on acetaminophen and the ibuprofen capsule sheet, coating capsule sheet is carried out the fragility test.Following table has been summed up dispersion and coating conditions and fragility test result:
31 32 33
Deionized water 1011.1 grams 1011.1 grams 1011.1 grams
Hydration time 1.75 hours 1.25 hours＞1 hour
The capsule sheet
1 kilogram 1 kilogram 1 kilogram of acetaminophen
1 kilogram 1 kilogram 1 kilogram of ibuprofen
Spraying condition
Inlet temperature 70-71 ℃ 71-75 ℃ 70-73 ℃
Outlet temperature 32-33 ℃ 31-32 ℃ 33-34 ℃
Chassis rotating speed 9-13rpm 10-14rpm 9-12rpm
57 minutes 56 minutes＞50 minutes time
Coat weight % 3% 3% 3%
Fragility test (10 minutes)
Acetaminophen 0% 0% 0%
Ibuprofen 0% 0% 0%
Embodiment 34
The dried component of present embodiment done mixes, obtain dried coated composition as shown in the table:
Weight (gram)
Avicel PH-105 33
ι chondrus ocellatus Holmes polysaccharide 10
Hydroxyethyl-cellulose 20
PGAa 4
Pluronic F-68 3
Alginate propylene glycol (Protonal Ester SD-LB, Pronova)
This dry preparation is dispersed in the deionized water, in the dispersion liquid that obtains, adds glyceryl triacetate and red #40 dispersion liquid (Crompton and Knowles) successively.Then this dispersion liquid is sprayed onto on the capsule sheet, and coated tablet is carried out the fragility test.Following table has been summed up used dispersion, coating and test condition in the present embodiment:
Glyceryl triacetate 23 grams
Red #40 dispersion liquid 7 grams
Deionized water 1011.1 grams
Hydration time 1.5 hours
The capsule sheet
2 kilograms of acetaminophen
Spraying condition
Inlet temperature 82-87 ℃
Outlet temperature 37-42 ℃
Chassis rotating speed 13-15rpm
55 minutes time
Coat weight % 3%
Fragility test (10 minutes)
Acetaminophen 0%
Embodiment 35
According to the method for embodiment 19, the component of this embodiment is done mixed.To do dark compound and be dispersed in the deionized water, be sprayed at then on capsule sheet and/or the tablet, and carry out the fragility test.This embodiment is summarized in following table:
Composition weight (gram)
Avicel PH-105 37
ι chondrus ocellatus Holmes polysaccharide 14.5
Hydroxyethyl-cellulose 22
Mannitol a15.5
Pluronic F-68 3
Blue (Blue Lake) #2 8 that forms sediment
Deionized water 1150
Hydration time 2.5 hours
The capsule sheet
1 kilogram of ibuprofen
1 kilogram of acetaminophen
Spraying condition
Inlet temperature 68-74 ℃
Outlet temperature 30-33 ℃
Chassis rotating speed 12-14rpm
60 minutes time
Coat weight % 3%
Fragility test (10 minutes)
Ibuprofen 0%
Chlorphenamine 0%
aThe mannitol granule
The gained tablet has splendid distribution of color and glossiness.The removal time of acetaminophen capsule sheet in 37 ℃ of deionized waters was less than 5 minutes.
Following table 1 has been enumerated other compositionss embodiment in the scope of the invention.
Table 1
Embodiment 36 37 38 39 40 41 42 43 44 45 46 47
Composition
Microcrystalline Cellulose 5 7 9 9 9 9 9 10 10 12.3 13 15
The ι chondrus ocellatus Holmes polysaccharide 15 15 14 14 14.5 14.5 15 10 14 14.7 14 14
Polyvinyl pyrrolidone 16 12 14 14 a 14 10 14 14 14 10 5 5
Hydroxyethyl-cellulose
Lecithin b 2 3 2.5 3 2.5 2 2 3 2 3 5 3
Lactose 60 60 60 60 60 64 60 60 60 60 60 60
Maltrin M-180
(various) pigment/dye 2 3 3 3 3
Other
Pulvis Talci 0.5 0.5
PGA c
Dicalcium phosphate
Croscarmellose
PEG d
Add up to 100 100 100 100 100 100 100 100 100 100 100 100
Table 1 (continuing)
Embodiment 48 49 50 51 52 53 54 55 56 57 58
Composition
Microcrystalline Cellulose 15 15 20 25 25 7 33 35 34.3 33-36 37.3
The ι chondrus ocellatus Holmes polysaccharide 14 14.5 15 10 15 16 17 15 14.7 15-17 14.7
Polyvinyl pyrrolidone 7.5 7.5 14 11
Hydroxyethyl-cellulose 20 22 22 22 22 12 22
Lecithin b 3 3 5 7 8 3 10 7 8-10
Lactose 60 60 35 67 8 8 9
Maltrin M-180 3 3 3 3 3
(various) pigment/dye 5 12 10 7 10 4-5 10
Other
Pulvis Talci 0.5
PGA c 7 7
Dicalcium phosphate 15
Croscarmellose 2
PEG d 34-35 34
Add up to 100 100 100 100 100 100 100 100 100 100 100
A Kollldon  Va-64:PVP+ acrylate
B hydroxylation soybean lecithin
c Profoam，Pronova
The d Polyethylene Glycol
Comparative Example A An
2.0 gram methyl hydroxybenzoates and 0.2 gram propylparaben are dissolved in the 100 gram propylene glycol.After dissolving is finished, 30.0 gram ι chondrus ocellatus Holmes polysaccharides (Viscarin SD-389, FMC Corporation) are dispersed in the propylene glycol solution.This dispersion liquid is added in the 1800 gram deionized waters then, stir, make the abundant hydration of chondrus ocellatus Holmes polysaccharide.Microscopy confirms chondrus ocellatus Holmes polysaccharide hydration fully.From aqueous solution, take a sample, place on the microscope slide drying.Obtain coherent film not only regular but also that have certain intensity like this., when this aqueous solution is sprayed onto on the tablet core core, to examining the bonding just poor of core.
Comparative Examples B
In 1300 gram deionized waters, 9.30 gram microcrystalline Cellulose (AvicelPH-102, FMC Corporation) and 20.7 gram ι chondrus ocellatus Holmes polysaccharides (Viscarin SD-389) are made dispersion liquid with Scott Turbon mixer.In this dispersion liquid, add 0.50 gram FD﹠amp; C aluminum color lake is dissolved in 25 milliliters of alcoholic acid solution.Have 0.125 gram methyl hydroxybenzoate and the 0.0125 gram propylparaben that add this dispersion liquid simultaneously are dissolved in the solution of 62 gram propylene glycol.To whole preparation restir 1 hour, be sprayed on then on the tablet core core.The bonding force of this coating is poor usually.
Though the present invention is elaborated, and have specific embodiment for reference, clearly, the personnel in this field of being familiar with can make various changes and change to it and not deviate from the spirit and scope of the present invention.

Claims (29)

  1. One kind edible, can sclerosis, the coated composition of the solid dosage forms of immediate release drug or veterinary drug, the mean diameter that said composition comprises 3%-40% is lower than 100 microns microcrystalline Cellulose, the chondrus ocellatus Holmes polysaccharide of film formation amount, and at least a reinforcement polymer, plasticizer or surfactant, when being ingested or place aqueous medium, described coated composition can significantly not postpone active component and discharge from the substrate that is wrapped with this coating, and the chondrus ocellatus Holmes polysaccharide of described film formation amount is 9-25%.
  2. 2. according to coated composition described in the claim 1, it is characterized in that it comprises the microcrystalline Cellulose of 5%-25%, the ι chondrus ocellatus Holmes polysaccharide of 10%-16% and the hydroxylation soybean lecithin of 2%-10%.
  3. 3. according to coated composition described in the claim 2, it is characterized in that it comprises the lactose of 35%-70%.
  4. 4. according to coated composition described in the claim 3, it is characterized in that it further comprises the propylene glycol alginate of 5%-10%.
  5. 5. according to coated composition described in the claim 2, it is characterized in that it comprises hydroxyethyl-cellulose or the polyvinyl pyrrolidone of 5%-22%.
  6. 6. according to coated composition described in the claim 5, it is characterized in that it further comprises the stain of 2%-10%.
  7. 7. according to coated composition described in the claim 1, it is characterized in that it comprises the microcrystalline Cellulose of 5%-10%, the ι chondrus ocellatus Holmes polysaccharide of 14%-16%, the hydroxylation soybean lecithin of 2%-4%, the lactose of 65%-70% and the propylene glycol alginate of 5%-10%.
  8. 8. according to coated composition described in claim 1 or 2, it is characterized in that MCC: the CGN weight ratio at 15: 85 in 60: 40 scope.
  9. 9. according to coated composition described in the claim 1, it is characterized in that it comprises the microcrystalline Cellulose of 30%-40%, the ι chondrus ocellatus Holmes polysaccharide of 10%-20% and the hydroxyethyl-cellulose of 12%-25%.
  10. 10. according to coated composition described in the claim 9, it is characterized in that it further comprises the stain of 2%-10%.
  11. 11., it is characterized in that it further comprises the hydroxylation soybean lecithin of 5%-10% and the lactose of 5%-10% according to coated composition described in the claim 10.
  12. 12., it is characterized in that it further comprises the Polyethylene Glycol of 30%-35% according to coated composition described in the claim 10.
  13. 13., it is characterized in that it comprises the microcrystalline Cellulose of 30%-40%, the ι chondrus ocellatus Holmes polysaccharide of 10%-20%, the polyvinyl pyrrolidone of 10%-15% and the Polyethylene Glycol of 30%-40% according to coated composition described in the claim 1.
  14. 14., it is characterized in that it further comprises the stain of 2%-10% according to coated composition described in the claim 13.
  15. 15., it is characterized in that described reinforcement polymer is at least a material that is selected from hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl methyl fiber and the polyvinyl pyrrolidone according to coated composition described in the claim 1.
  16. 16. according to coated composition described in the claim 1, it is characterized in that described surfactant is at least a material that is selected from sodium lauryl sulphate, hydroxylation soybean lecithin, tween (polysorbates) and the propylene oxide-ethylene oxide block copolymer.
  17. 17., it is characterized in that it further comprises the filler that is selected from lactose or maltodextrin according to coated composition described in the claim 1.
  18. 18., it is characterized in that described plasticizer is at least a material that is selected from Polyethylene Glycol, glyceryl triacetate, dibutyl sebacate, propylene glycol, sorbitol, glycerol and the triethyl citrate according to coated composition described in the claim 1.
  19. 19. one kind edible, can sclerosis, the coated composition of the solid dosage forms of immediate release drug or veterinary drug, said composition comprises the microcrystalline Cellulose of 3%-40%, the chondrus ocellatus Holmes polysaccharide of film formation amount, and at least a reinforcement polymer, plasticizer or surfactant, when being ingested or place aqueous medium, described coated composition can significantly not postpone active component and discharge from the solid dosage forms that is wrapped with this coating, and the chondrus ocellatus Holmes polysaccharide of described film formation amount is 9-25%.
  20. 20. the method to medicine or veterinary drug solid dosage forms coating comprises such step: make the described coated composition hydration of claim 1, the coated composition with described hydration is coated on described medicine or the veterinary drug solid dosage forms then.
  21. 21. method according to claim 20, wherein said hydration time are 0.5-3 hour.
  22. 22. one kind by the medicine or the veterinary drug solid dosage forms of the described coated composition of claim 1 institute coating.
  23. 23. coated composition according to claim 1, it further comprises filler, and wherein said filler is a carbohydrate.
  24. 24. one kind by the medicine of the described coated composition coating of claim 19 or veterinary drug solid dosage forms.
  25. 25. medicine according to claim 22 or solid dosage forms, wherein said pharmaceutical solid dosage forms is a nutrient drug.
  26. 26. medicine according to claim 22 or veterinary drug solid dosage forms, wherein said coated composition further comprises the carbohydrate filler.
  27. 27. medicine according to claim 22 or veterinary drug solid dosage forms, it comprises the 5-25% microcrystalline Cellulose, the hydroxylation soybean lecithin of 2%-10% and 35-70% lactose.
  28. 28. medicine according to claim 22 or veterinary drug solid dosage forms, wherein said medicine or veterinary drug solid dosage forms are tablets.
  29. 29. medicine according to claim 24 or veterinary drug solid dosage forms, wherein said medicine or veterinary drug solid dosage forms are tablets.
CNB008150168A 1999-10-29 2000-08-04 Edible coating composition Expired - Fee Related CN1188114C (en)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US16251499P 1999-10-29 1999-10-29
US60/162,514 1999-10-29
US16740799P 1999-11-24 1999-11-24
US60/167,407 1999-11-24
US17252699P 1999-12-17 1999-12-17
US60/172,526 1999-12-17
US09/491,724 US6432448B1 (en) 1999-02-08 2000-01-27 Edible coating composition
US09/491,724 2000-01-27

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CN1188114C true CN1188114C (en) 2005-02-09

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CN113455577A (en) * 2020-03-31 2021-10-01 仙乐健康科技股份有限公司 Health food, functional food or special dietary food and preparation method thereof

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AU6521300A (en) 2001-05-14
IL149282A0 (en) 2002-11-10
CN1384736A (en) 2002-12-11
AR025070A1 (en) 2002-11-06
JP2003527335A (en) 2003-09-16
TR200201112T2 (en) 2002-12-23
WO2001032150A1 (en) 2001-05-10
IL149282A (en) 2010-05-31
EP1231901A1 (en) 2002-08-21
BR0014966A (en) 2002-07-02

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