CN105832671A - Dry suspension for controlled-release of medicine and preparation method of dry suspension - Google Patents
Dry suspension for controlled-release of medicine and preparation method of dry suspension Download PDFInfo
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- CN105832671A CN105832671A CN201610234640.8A CN201610234640A CN105832671A CN 105832671 A CN105832671 A CN 105832671A CN 201610234640 A CN201610234640 A CN 201610234640A CN 105832671 A CN105832671 A CN 105832671A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
-
- 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
Abstract
The invention discloses a dry suspension for controlled-release of a medicine and a preparation method of the dry suspension. The dry suspension comprises 15-80% of combined sustained-release pellets and 20-85% of suspending particles. The combined sustained-release pellets are prepared from two pellets with different medicine release speeds according to a certain ratio. In the suspending particles, the ratio of a suspending agent is 2-40% of that of the suspending particles, the ratio of a sweetening agent is 0.1-4% of that of the suspending particles, and the ratio of the other components is 60-90% of that of the suspending particles. Through the dry suspension, the controlled-release of a medicine can last for 12 h. The dry suspension can be made into a suspension with a proper amount of warm water. The suspension is good in suspension effect, accurate in dose, and good in stability, tastes sweet, and is convenient for children to drink.
Description
Technical field:
The present invention relates to sustained release preparation technical field, particularly relate to composition and the preparation side thereof of a kind of slow-release dry suspension
Method.
Background technology:
According to the physilogical characteristics of children, the children of different age group are suitable for different pharmaceutical preparations.As: infant's first-selection sugar
Slurry and drops；2-5 year children can use syrup, supensoid agent, solution and effervescent agent, and tablet and capsule can cause swallowing tired
Difficult or bring the damage of esophagus；6-11 year children can use oral disnitegration tablet, chewable tablet and coating tablet.But above-mentioned preparation is both needed to
Within one day, take repeatedly, be administered the problem bringing compliance to children frequently.Due to the shortage of children kind, for a long time
Since children all substitute with the medicine of adult, dosage is according to age, body weight, body surface area and the adult of children
Ratio empirically carry out converting and obtaining.The shortage of children causes children to use adult's medicine to become universal phenomenon, brings
Serious drug safety hidden danger.
The main clinical manifestation of respiratory disease is cough, asthma, expectoration etc..Phlegm is the secretion of respiratory tract, normally
The sputum of people is little, keeps the mucus that respiratory tract is moistening the most on a small quantity.When human body sucks dust, irritative gas, pathogenic germ
During with virus, the sputum of respiratory tract secretion is consequently increased, and sputum can become yellow dense phlegm.Guaiacol glycerol ether is conventional dispelling
Phlegm medicine.The entitled 3-of chemistry (2-methoxyphenoxy) propane-1 of guaiacol glycerol ether, 2-glycol, also known as more create glycerine
Ether.This medicine is soluble in ethanol, is slightly soluble in water, has bitter taste, and rapid in gastrointestinal absorption, the half-life is 1h.Its mechanism of action is:
By stimulating the Vagal Afferent Fibers of stomach lining, reaching oblongata vomiting centre, reflexive gas-distribution pipe is with bronchial
Descending vagal efferent, makes tracheae increase with bronchus glandular secretion, dilutes sputum so that it is be prone to expectoration.Guaiacol is sweet
Oil ether child dose be: 2-6 year every 4 hours 50-100mg of children, 24 hours be less than 600mg；Every 4 hours of 6-12 year children
100-200mg, is less than 1200mg in 24 hours.CN 103222971 discloses the oral administration solution of a kind of guaiacol glycerol ether,
Although this formulation medication is easy, but still needs to the most secondary administration, compliance is poor, is unfavorable for children taking.CN100389757 is public
Having opened a kind of guaiacol glycerol ether oral drop pills, this formulation has that drugloading rate is big, rapid-action, production technology is the most special
Point, but still need to the most secondary administration, however it remains the problem that compliance is poor.It is sweet that US 6372252 discloses a kind of guaiacol
Oil ether sustained release tablets, this tablet is double-layer sustained release tablets, is made up of release layer and slow release layer.After medication, release layer discharges rapidly, sustained release
The medicine of layer slowly discharges from skeleton, can reach the effect of 12 hours sustained releases.Although sustained release tablets has long-acting Medicinal Trait,
But this sustained release tablets nearly weighs 720mg, volume is 16mm × 10mm × 6mm, and volume is relatively big, is unfavorable for the patient of children and dysphagia
Take, children's dysphagia or damage esophagus can be caused.CN1994285 discloses a kind of sustained release micro-pellet of guaifenesin,
Said preparation prepares medicine carrying micropill by the method for extrusion spheronization, uses the mode of spray at the bottom of fluid bed to be coated with slow release layer and prepares sustained release
Ball, then it is coated with release layer on the basis of sustained release ball, reach the effect of quick-release and sustained release, but prepared micropill gross weight 1000mg, micro-
Pill footpath, between 0.7-1.0mm, yet suffering from volume relatively greatly if being administered after encapsulating capsule, being unfavorable for the trouble of children and dysphagia
The problem that person takes；If directly using, guaiacol glycerol ether has bitter taste and sand type, is unfavorable for children taking.
CN102266293 A, CN101829045 A, CN102232928 A etc. disclose the slow-release dry suspension of multi-medicament, above-mentioned
Patent of invention packs after directly mixing with suspending agent, flavouring after making sustained release pellet, has that sustained release pellet is easy and suspending
Agent, the problem of flavouring layering, may bring micropill suspension the best, the underproof problem of the medicament contg uniformity.
Summary of the invention:
It is an object of the invention to provide slow-release dry suspension of a kind of medicine and preparation method thereof, slow-release dry suspension by
Combination sustained release pellet and suspending particle composition.This dry suspensoid agent includes combining sustained release pellet 15%-80%, suspending particle 20%-
85%, suspending particle means the granular particle obtained by suspending agent by granulating process.This dry suspensoid agent adds water before taking
Obtaining suspension after shaking up, dosage is accurate, has sweet taste, it is possible to resolve the problem of children's Compliance.
The slow-release dry suspension of medicine of the present invention, described medicine is selected from the medicine for the treatment of respiratory disease.
The slow-release dry suspension of medicine of the present invention, described medicine is selected from expectorant, also can be selected for antitussive, relievings asthma
Medicine, expectorant, anti-inflammatory agent etc..
The slow-release dry suspension of medicine of the present invention, described medicine is selected from nauseous expectorant, also can be selected for excitant
Expectorant, sputum lytic agent, sputum diluent etc..
The slow-release dry suspension of medicine of the present invention, described medicine is selected from guaiacol glycerol ether.
The slow-release dry suspension of medicine of the present invention is a kind of slow-release dry suspension being easy to children taking, preferably more wound
Wood phenol glycerin ether slow-release dry suspension.
In the medicine that children commonly use, the effective dose of guaiacol glycerol ether is bigger, it is desirable to the sustained release pellet made carries
Dose is higher, and the weightening finish of medicine-feeding process is relatively big, and therefore technology difficulty is bigger.The present invention has selected guaiacol glycerol ether to be model
Medicine, it is provided that the preparation method of a kind of slow-release dry suspension being easy to children taking, builds a kind of sustained release being easy to children taking
The technology platform of dry suspensoid agent preparation method is it can also be used to other children's common drugs, to prepare slow-release dry suspension.
Break by the teeth when taking guaiacol glycerol ether slow-release dry suspension the risk of sustained release pellet to reduce children, simultaneously
Ensure higher drugloading rate, therefore select the blank capsule core medicine-feeding that particle diameter is less, prepare that drugloading rate is relatively big and that particle diameter is less is slow
Release micropill.The specification of sustained release micro-pellet of guaifenesin prepared by the present invention is every bag of 150mg, can fit according to the age of children
When the bag number that selection is taken, dosage is accurate, can avoid taking half bag of inaccurate problem of the dosage brought.In order to allow children taking
After guaiacol glycerol ether slow-release dry suspension, number of times is taken in energy rapid-onset and minimizing, and sustained release pellet part of the present invention is by two kinds
The micropill of different drug release rates combines, and release micropill faster can ensure that early stage quickly discharges, and reaches treatment effect in early days
Really, the slower micropill of release can maintain the release of 12h, maintaining treatment effect.In order to prevent supensoid agent from leading with sustained release pellet layering
The defective problem the best with suspension of uniformity of dosage units caused, the present invention is not by sustained release pellet and suspending agent, flavouring
Simple mixing, but supensoid agent is made the suspending grain close with sustained release pellet density and particle diameter with other compositions by granulation
Son, reduces the risk of layering.Additionally, from the angle of environmental protection with safety, the present invention is also with suspension medicine-feeding of spraying water at the bottom of fluid bed
Mode prepares guaiacol glycerol ether medicine carrying micropill, and technique reappearance is relatively strong, and controllability is preferable.
The guaiacol glycerol ether slow-release dry suspension of the present invention, it is characterised in that by weight percentage, by guaiaci lignum
Phenol glycerin ether combination sustained release pellet 15%-80%, suspending particle 20%-85% composition.In described suspending particle, suspending agent accounts for
The 2%-40% of suspending particle, sweetener accounts for the 0.1%-4% of suspending particle, and other compositions account for the 60%-90% of suspending particle.
Sustained release micro-pellet of guaifenesin of the present invention is that the component based on following weight is made:
A. guaiacol glycerol ether medicine carrying micropill
Wherein guaiacol glycerol ether medicine carrying micropill consists of the following composition:
Guaiacol glycerol ether: 40%-80%
Blank capsule core: 20%-60%
Adhesive: 0.1%-10%
Owing to the effective dose of guaiacol glycerol ether is relatively big, therefore require that the drugloading rate of sustained release pellet made is higher.
B. guaiacol glycerol ether isolation micropill
Separation layer weight is the 2%-20% of medicine carrying micropill weight, preferably 5%-15%.
Wherein separation layer consists of the following composition:
Film forming agent: 50%-100%
Antitackiness agent: 0%-50%
The effect of separation layer is: 1) owing to the smoothness on guaiacol glycerol ether medicine carrying micropill surface may not, bag
The more smooth rounding in micropill surface can be made after covering barrier gown, be beneficial to next step sustained release coating；2) separation layer can prevent slow release layer bag
During clothing, guaiacol glycerol ether infiltrates through slow release layer and causes medicine to discharge in advance, or avoids guaiacol glycerol ether and sustained release
Layer material directly contacts the chemical stability problems brought.
C. sustained release micro-pellet of guaifenesin
Slow release layer weight is the 2%-60%, preferably 2%-50% of isolation micropill weight.
Wherein slow release layer consists of the following composition:
Slow releasing function can not be played when slow release layer weightening finish is relatively low, but when sustained release weightening finish is too high, 12h release is incomplete, therefore
The present invention finally determines the 2%-60% that slow release layer coating weight gain is isolation micropill weight.
D. guaiacol glycerol ether combination sustained release pellet is combined by a certain percentage by two kinds of different drug release rate micropills:
The very fast micropill of release accounts for the 10%-50% of micropill gross weight,
The slower micropill of release accounts for the 50%-90% of micropill gross weight.
Release micropill faster can ensure that early stage quickly discharges, and reaches result for the treatment of in early days, and the slower micropill of release can
Maintain the release of 12h, maintaining treatment effect.
The most described release micropill faster can be guaiacol glycerol ether medicine carrying micropill, guaiacol glycerol ether isolation micro-
Ball or the sustained release less sustained release pellet of weightening finish, the preferably less sustained release pellet of sustained release weightening finish, it quickly discharges except providing early stage
May also function as outward the effect of taste masking.
The blank capsule core of guaiacol glycerol ether medicine carrying micropill, selected from sucrose capsule core, microcrystalline cellulose capsule core, starch capsule core
In one or more, preferably sucrose capsule core；Described adhesive is selected from HPMC, hydroxypropyl cellulose, polyethylene
One or more in pyrrolidones, preferably HPMC.
The separation layer film forming agent of sustained release micro-pellet of guaifenesin is HPMC, hydroxypropyl cellulose, first
One or more in base acrylic resin copolymer.One or more in talcum powder, superfine silica gel powder of antitackiness agent.Anti-glutinous
The use of agent is possible to prevent the adhesion in separation layer coating process between micropill.
Slow-release material in sustained release micro-pellet of guaifenesin slow release layer is methacrylic resin copolymer, ethyl fibre
One or more in dimension element, preferred, ethyl.Additionally, polyvinyl acetate ester aqueous dispersion also can operate with sustained release coating
In.Described pore-foaming agent is the one in lactose, sucrose, polyvinylpyrrolidone, HPMC, polyethylene glycol or several
Kind.Described plasticizer be the one in triethyl citrate, polyethylene glycol, dibutyl sebacate, diethyl phthalate or
Several.The use of plasticizer can reduce slow-release material glass transition temperature.Simple use ethyl cellulose is as slow-release material
Time, the slow releasing function of ethyl cellulose is too strong, may cause insoluble drug release the most out, releases so needing to add pore-foaming agent regulation
Put.Methacrylic resin copolymer itself has permeability, therefore need not add pore-foaming agent regulation release, can be slow by regulation
Release weightening finish and control the release of medicine.Described antitackiness agent is a kind of or several in talcum powder, superfine silica gel powder, glycerin monostearate
Kind, preferably talc powder.The use of antitackiness agent is possible to prevent the adhesion in slow release layer coating process between micropill.
The suspending particle of guaiacol glycerol ether slow-release dry suspension is become to be grouped into other by suspending agent, sweetener.Its
His composition includes filler, adhesive, disintegrant, pigment.Described suspending agent is xanthans, Arabic gum, sodium alginate, card ripple
One or more in nurse.Described sweetener is one or more in Aspartame, Steviosin, saccharin sodium, Sucralose.Institute
Stating filler is one or more in sucrose, microcrystalline cellulose, glucose, lactose.Described adhesive is hydroxypropyl methylcellulose
One or more in element, hydroxypropyl cellulose, copolyvidone.Described disintegrant is Ac-Di-Sol, cross-links and gather
One or more in vinylpyrrolidone, crosslinked carboxymethyl fecula sodium, low-substituted hydroxypropyl cellulose.For prevent supensoid agent with
The defective problem the best with suspension of the sustained release pellet uniformity of dosage units that causes of layering, the present invention be not by sustained release pellet with
Suspending agent, flavouring simply mix, but supensoid agent and other compositions are made and sustained release pellet density and grain by granulation
The suspending particle that footpath is close, reduces the risk of layering.
The suspending particle of guaiacol glycerol ether slow-release dry suspension is by following by suspending agent, sweetener and other compositions
The component of weight meter is made:
Due to guaiacol glycerol ether slightly bitter taste, the addition of sweetener can be covered the bitter taste of guaiacol glycerol ether, carry
The compliance that high children take medicine.The consumption of suspending agent is 2%-40%, and the consumption of suspending agent is too small, may cause suspendible effect not
Good, sustained release pellet free settling；When the consumption of supensoid agent is excessive, the mobility that may cause suspension is the best.Except xanthans, I
Outside the suspending agents such as primary glue, sodium alginate, carbomer, gellan gum heating be i.e. dissolved into transparent solution, after cooling, formed transparent and
Solid gel, can act also as the material of supensoid agent.The viscosity of dry suspensoid agent can regulate the consumption of suspending agent as required.Bonding
The yield of suspending particle when the addition of agent can improve granulation.The addition of disintegrant can be when using mixing in water for oral taking, and disintegrant can collapse rapidly
Open, make suspendible material play rapidly the effect of suspendible.The addition of a small amount of pigment can improve the outward appearance of supensoid agent.
Guaiacol glycerol ether slow-release dry suspension of the present invention, it is characterised in that be prepared as follows and
Become:
A. the preparation of guaiacol glycerol ether medicine carrying micropill
Guaiacol glycerol ether, adhesive are dissolved in the ethanol solution of 50%-90% or are suspended in water, and suspendible is uniform,
Continuously stirred, the capsule core of 0.18-0.50mm is placed in fluid bed, uses the mode of spray at the bottom of fluid bed to add medicine to, coating ginseng is set
Number, constantly adjusts each parameter, makes micropill have good fluidized state during medicine-feeding.
Break by the teeth when taking guaiacol glycerol ether slow-release dry suspension the risk of sustained release pellet to reduce children, simultaneously
Ensure higher drugloading rate, therefore select the blank capsule core medicine-feeding that particle diameter is less.
B. the preparation of guaiacol glycerol ether isolation micropill
Being suspended in ethanol solution or the water of 50%-90% by separation layer coating material, suspendible is uniform, continuously stirred, system
Becoming solid content to be about the coating solution of 4%-18%, medicine carrying micropill uses the mode bag separation layer of spray at the bottom of fluid bed, during constantly
Adjust each parameter, prepare guaiacol glycerol ether isolation micropill.
C. the preparation of sustained release micro-pellet of guaifenesin
Slow release layer coating material being dissolved in the ethanol solution of 70%-90% or is suspended in water, suspendible is uniform, persistently stirs
Mix, make the coating solution that solid content is about 4%-20%, guaiacol glycerol ether is isolated micropill and uses the side of spray at the bottom of fluid bed
Formula bag extended release coatings, during constantly adjust each parameter, prepare sustained release micro-pellet of guaifenesin.Sustained release pellet adds about
Talcum powder, magnesium stearate or the superfine silica gel powder of 1%, prevents micropill adhesion during storing.
D. the micropill mixing of different rate of releasing drug
Being mixed according to a certain percentage by two kinds of different drug release rate micropills and obtain combining sustained release pellet, wherein release is relatively
Fast micropill accounts for the 10%-50% of micropill gross weight, and the slower micropill of release accounts for the 50%-90% of micropill gross weight.
E. the preparation of suspending particle
After suspending agent, sweetener, filler, adhesive, disintegrant, pigment are mixed.By dry granulation mechanism
Become particle.F. combination sustained release pellet and the mixing of suspending particle
Guaiacol glycerol ether is combined sustained release pellet and becomes slow-release dry suspension with suspending mix particles, wherein guaiacol
Glycerin ether combination sustained release pellet accounts for 15%-80%, suspending particle 20%-85%.
The present invention uses the mode of spray at the bottom of fluid bed to be prepared for sustained release micro-pellet of guaifenesin, but also can use centrifugal
The mode of granulation prepares guaiacol glycerol ether medicine carrying micropill, and the time of guaiacol glycerol ether medicine carrying micropill is prepared in shortening.
The guaiacol glycerol ether slow-release dry suspension of the present invention solves the problem that the related preparations of prior art exists.
Guaiacol glycerol ether slow-release dry suspension by combining sustained release pellet, suspending particle forms, warm water stirs and can take, energy
Enough 12 hours sustained release, are suitable for children taking, improve the compliance that children take medicine by suspending particle pleasantly sweet dose.
The assay method of guaiacol glycerol ether slow-release dry suspension release is molten according to Chinese Pharmacopoeia version four in 2015
The regulation of out-degree and drug release determination method the first method is tested.Take the guaiacol glycerol ether slow-release suspension that suspendible is good, put
In turning in basket, with the water of 900ml as dissolution medium, rotating speed is 100rpm, and temperature is 37 ± 0.5 DEG C, respectively at 1h, 2h, 4h,
6h, 8h, 12h sample 10ml, and the dissolution medium of supplementary equal-volume isothermal, and sample filters through 0.8 μm miillpore filter, and it is right separately to weigh
According to the solution of product configuration debita spissitudo, calculate accumulative releasing degree according to external standard method.
Accompanying drawing explanation
Fig. 1 is embodiment one guaiacol glycerol ether slow-release dry suspension release profiles in aqueous medium
Fig. 2 is embodiment two guaiacol glycerol ether slow-release dry suspension release profiles in aqueous medium
Fig. 3 is embodiment three guaiacol glycerol ether slow-release dry suspension release profiles in aqueous medium
Detailed description of the invention
In order to make those skilled in the art be better understood from the technological invention of the present invention, below in conjunction with specific embodiment and
Accompanying drawing describes the present invention in detail.The explanation of following example is only intended to help to understand method and the core concept thereof of the present invention.
It should be pointed out that, for those skilled in the art, under the premise without departing from the principles of the invention, it is also possible to right
The present invention carries out some modifications and improvement, and these are modified and improve also to fall within the scope of the invention as claimed.
Embodiment one
1. the preparation of medicine carrying capsule core
The proportioning of each component of medicine carrying capsule core is as follows:
Preparation process:
After HPMC is dissolved in water, adds guaiacol glycerol ether and be configured to suspension, by 0.3-0.425mm
Sucrose capsule core is placed in fluid bed, uses the mode of spray at the bottom of fluid bed to add medicine to, and medicine-feeding weightening finish, to 100%, arranges coating parameter, on
Constantly adjust each parameter during medicine, make micropill have good fluidized state.In the present embodiment, adhesive is that hydroxypropyl is fine
Dimension element, it is also possible to select one or more in polyvinylpyrrolidone, hydroxypropyl cellulose.
2. isolate the preparation of micropill
Preparation process:
The HPMC of recipe quantity, talcum powder are added to the water so that it is after dispersed, continuously stirred, use
Spraying mode bag separation layer at the bottom of fluid bed, isolation weightening finish, to 5%, constantly adjusts each parameter, makes micropill have during bag separation layer
Good fluidized state.
3. the preparation of sustained release pellet
Preparation process:
The water of recipe quantity is added in Surlease aqueous dispersion, dispersed after, isolation micropill is placed in fluid bed,
Arranging coating parameter, use and spray mode bag slow release layer at the bottom of fluid bed, increase weight to 3% taking-up part sustained release pellet, residue micropill increases
Weight to 25%, during constantly adjust each parameter, it is ensured that the fluidized state that micropill is good.
4. combine the preparation of sustained release pellet
The sustained release pellet of sustained release weightening finish 3% is mixed according to the ratio of 40: 60 with the sustained release pellet of weightening finish 25%
To combination sustained release pellet.
5. the preparation of suspending particle
Preparation process:
After being mixed by above-mentioned auxiliary material, make particle by dry granulating machine.In the present embodiment, suspending agent is xanthans,
One or more in Arabic gum, sodium alginate, carbomer can also be selected.In the present embodiment, filler is sucrose, it is possible to
To select one or more in microcrystalline cellulose, glucose, lactose.In the present embodiment, sweetener is Aspartame, it is also possible to
Select one or more in Steviosin, saccharin sodium, Sucralose.In the present embodiment, adhesive is copolyvidone, it is also possible to choosing
By one or more in hydroxypropyl cellulose, HPMC.In the present embodiment, disintegrant is cross-linked carboxymethyl fiber
Element sodium, it is also possible to select the one in low-substituted hydroxypropyl cellulose, PVPP, crosslinked carboxymethyl fecula sodium
Or it is several.
5. the preparation of slow-release dry suspension
After combination sustained release pellet is mixed in the ratio of 20: 80 with suspending particle, pack.
Embodiment two
1. the preparation of medicine carrying capsule core
The proportioning of each component of medicine carrying capsule core is as follows:
Preparation process:
Guaiacol glycerol ether, hydroxypropyl cellulose are dissolved in ethanol/water solution, by 0.18-0.25mm sucrose capsule core
Being placed in fluid bed, use the mode of spray at the bottom of fluid bed to add medicine to, medicine-feeding weightening finish, to 100%, arranges coating parameter, during medicine-feeding
Constantly adjust each parameter, make micropill have good fluidized state.In the present embodiment, adhesive is hydroxypropyl cellulose, it is also possible to
Select one or more in HPMC, polyvinylpyrrolidone.
2. isolate the preparation of capsule core
Preparation process:
The HPMC of recipe quantity is added in ethanol/water mixed solution so that it is after dispersed, add talcum
Powder, continuously stirred, use and at the bottom of fluid bed, spray mode bag separation layer, during bag separation layer, constantly adjust each parameter, isolation weightening finish
Coating is stopped after 15%.
3. the preparation of sustained release pellet
Preparation process:
Recipe quantity is obtained ethyl cellulose, polyvinylpyrrolidone, the mixed solution of dibutyl sebacate addition water/ethanol
In, after dissolving, isolation micropill is placed in fluid bed, coating parameter is set, use mode bag slow release layer, the process of spraying at the bottom of fluid bed
In constantly adjust each parameter, it is ensured that the fluidized state that micropill is good, stop coating after sustained release weightening finish to 18%.
4. combine the preparation of sustained release pellet
The sustained release pellet of guaiacol glycerol ether medicine carrying micropill with weightening finish 18% is mixed according to the ratio of 30: 70
To combination sustained release pellet.
5. the preparation of suspending particle
Preparation process:
After being mixed by above-mentioned auxiliary material, make particle by dry granulating machine.In the present embodiment, suspending agent is alginic acid
Sodium, it is also possible to select one or more in Arabic gum, xanthans, carbomer.In the present embodiment, filler is glucose, also
One or more in microcrystalline cellulose, sucrose, lactose can be selected.In the present embodiment, sweetener is Steviosin, it is also possible to choosing
By one or more in Aspartame, saccharin sodium, Sucralose.In the present embodiment, adhesive is hydroxypropyl cellulose, it is possible to
To select one or more in copolyvidone, HPMC.In the present embodiment, disintegrant is crosslinked polyethylene pyrroles
Alkanone, it is also possible to select the one in low-substituted hydroxypropyl cellulose, Ac-Di-Sol, crosslinked carboxymethyl fecula sodium
Or it is several.
6. the preparation of slow-release dry suspension
After combination sustained release pellet is mixed in the ratio of 40: 60 with suspending particle, pack.
Embodiment three
1. the preparation of medicine carrying capsule core
The proportioning of each component of medicine carrying capsule core is as follows:
Preparation process:
Guaiacol glycerol ether, polyvinylpyrrolidone are dissolved in ethanol solution, 0.35-0.50mm starch capsule core is put
In fluid bed, using the mode of spray at the bottom of fluid bed to add medicine to, medicine carrying increases weight to 100%, arranges coating parameter, during medicine-feeding not
The each parameter of disconnected adjustment, makes micropill have good fluidized state.In the present embodiment, adhesive is polyvinylpyrrolidone, in one
Plant or one or more can also selected in HPMC, hydroxypropyl cellulose several.
2. isolate the preparation of micropill
Preparation process:
The Eudragit EPO of recipe quantity, talcum powder are added in ethanol/water mixed solution so that it is after dispersed, hold
Continuous stirring, uses and sprays mode bag separation layer at the bottom of fluid bed, constantly adjusts each parameter, make micropill have well during bag separation layer
Fluidized state, isolation weightening finish is to stopping coating after 8%.
3. the preparation of sustained release pellet
Preparation process:
By water, talcum powder add recipe quantity Eudragit NE30D in, dispersed after, isolation micropill is placed in fluidisation
In Chuan, coating parameter is set, continuously stirred, use and spray mode bag slow release layer at the bottom of fluid bed, during constantly adjust each parameter, protect
The fluidized state that card micropill is good, stops coating after sustained release weightening finish to 45%.
4. combine the preparation of sustained release pellet
Guaiacol glycerol ether is isolated micropill mix according to the ratio of 30: 70 with the sustained release pellet of weightening finish 45%
To combination sustained release pellet.
5. the preparation of suspending particle
Preparation process:
After being mixed by above-mentioned auxiliary material, make particle by dry granulating machine.In the present embodiment, suspending agent is Arabic
Glue, it is also possible to select one or more in sodium alginate, xanthans, carbomer.In the present embodiment, filler is microcrystalline cellulose
Element, it is also possible to select one or more in glucose, sucrose, lactose.In the present embodiment, sweetener is saccharin sodium, it is also possible to choosing
By one or more in Aspartame, Steviosin, Sucralose.In the present embodiment, adhesive is hydroxypropyl cellulose, it is possible to
To select one or more in copolyvidone, HPMC.In the present embodiment, disintegrant is crosslinked carboxymethyl fecula
Sodium, it is also possible to select the one in low-substituted hydroxypropyl cellulose, PVPP, Ac-Di-Sol
Or it is several.
6. the preparation of slow-release dry suspension
After combination sustained release pellet is mixed in the ratio of 50: 50 with suspending particle, pack.
Claims (13)
1. the slow-release dry suspension of a medicine, it is characterised in that by weight percentage, by combination sustained release pellet 15%-
80%, suspending particle 20%-85% form；Described combination sustained release pellet is by two kinds of different drug release rate micropill groups by a certain percentage
Conjunction forms；In described suspending particle, suspending agent accounts for the 2%-40% of suspending particle weight, and sweetener accounts for suspending particle weight
0.1%-4%, other compositions account for the 60%-90% of suspending particle.
The most according to claim 1, the slow-release dry suspension of medicine, described medicine is selected from the medicine for the treatment of respiratory disease.
The most according to claim 1, the slow-release dry suspension of medicine, described medicine is selected from expectorant.
The most according to claim 1, the slow-release dry suspension of medicine, described medicine is selected from nauseous expectorant.
The most according to claim 1, the slow-release dry suspension of medicine, described medicine is selected from guaiacol glycerol ether.
The most according to claim 1, the slow-release dry suspension of medicine, the slow-release dry suspension of described medicine is that one is easy to
The slow-release dry suspension that child takes.
The slow-release dry suspension of medicine the most according to claim 6, described sustained release pellet component based on following weight makes:
A. guaiacol glycerol ether medicine carrying micropill
Guaiacol glycerol ether medicine carrying micropill consists of the following composition:
Guaiacol glycerol ether: 40%-80%
Blank capsule core: 20%-60%
Adhesive: 0.1%-10%
B. guaiacol glycerol ether isolation micropill
Separation layer weight is the 2%-20% of medicine carrying micropill weight
Wherein separation layer consists of the following composition:
Film forming agent: 50%-100%
Antitackiness agent: 0%-50%
C. sustained release micro-pellet of guaifenesin
Slow release layer weight is the 2%-60% of isolation micropill weight
Wherein slow release layer consists of the following composition:
D. guaiacol glycerol ether combination sustained release pellet is combined by a certain percentage by two kinds of different drug release rate micropills:
The very fast micropill of release accounts for the 10%-50% of micropill gross weight,
The slower micropill of release accounts for the 50%-90% of micropill gross weight；
The most described release micropill faster can be guaiacol glycerol ether medicine carrying micropill, guaiacol glycerol ether isolation micropill,
The sustained release less sustained release pellet of weightening finish.
The slow-release dry suspension of medicine the most according to claim 7, it is characterised in that guaiacol glycerol ether medicine carrying micropill
Blank capsule core, one or more in sucrose capsule core, microcrystalline cellulose capsule core, starch capsule core；Described adhesive is selected from hydroxyl
One or more in third methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone.
The slow-release dry suspension of medicine the most according to claim 7, it is characterised in that described separation layer film forming agent is hydroxypropyl
One or more in methylcellulose, hydroxypropyl cellulose, methacrylic resin copolymer；Antitackiness agent selected from talcum powder,
One or more in superfine silica gel powder, glycerin monostearate.
The slow-release dry suspension of medicine the most according to claim 7, it is characterised in that in described slow release layer, slow-release material is
One or more in methacrylic resin copolymer, ethyl cellulose；Described pore-foaming agent is lactose, sucrose, polyethylene pyrrole
One or more in pyrrolidone, HPMC, polyethylene glycol；Described plasticizer is triethyl citrate, poly-second two
One or more in alcohol, dibutyl sebacate, diethyl phthalate；Described antitackiness agent selected from talcum powder, superfine silica gel powder,
One or more in glycerin monostearate.
The slow-release dry suspension of 11. medicines according to claim 6, it is characterised in that suspending particle is by suspending agent, sweetener
Become to be grouped into other；Other compositions include filler, adhesive, disintegrant and/or pigment；Described suspending agent be xanthans,
One or more in Arabic gum, sodium alginate, carbomer；Described sweetener be Aspartame, Steviosin, saccharin sodium, three
One or more in chlorine sucrose；Described filler is one or more in sucrose, microcrystalline cellulose, glucose, lactose；Institute
Stating adhesive is one or more in HPMC, hydroxypropyl cellulose, copolyvidone；Described disintegrant is crosslinking
One in sodium carboxymethylcellulose, PVPP, crosslinked carboxymethyl fecula sodium, low-substituted hydroxypropyl cellulose
Or it is several；Described pigment is one or more in iron oxide yellow, iron oxide red, iron oxide brown.
12. according to the slow-release dry suspension of medicine described in claim 11, it is characterised in that suspending agent, sweetener and other compositions
Component based on following weight is made:
The preparation method of 13. slow-release dry suspensions of medicine according to claim 6, it is characterised in that comprise the following steps
Make:
1) by guaiacol glycerol ether and adhesive wiring solution-forming or suspension, in the way of spray at the bottom of fluid bed, guaiacol is sweet
Oil ether is coated in the capsule core of 0.18-0.50mm, prepares medicine carrying micropill；
2) use the mode of spray at the bottom of fluid bed, medicine carrying micropill is coated with separation layer, prepare isolation micropill；
3) use the mode of spray at the bottom of fluid bed, isolation micropill is coated with slow release layer, prepares sustained release pellet；
4) two kinds of different drug release rate micropills are combined by a certain percentage, obtain combining sustained release pellet；
4), after uniformly being mixed by outside auxiliary material, it is made into suspending particle by dry granulation；
5) guaiacol glycerol ether is combined sustained release pellet with suspending particle by following weight ratio: guaiacol glycerol ether combination is slow
Release and pack after micropill 15%-80%, suspending particle 20%-85% mix, prepare guaiacol glycerol ether slow release dry suspension composition
Agent.
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