CN107773555A - A kind of nifedipine micropore permeation pump particulate and preparation method thereof - Google Patents
A kind of nifedipine micropore permeation pump particulate and preparation method thereof Download PDFInfo
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- CN107773555A CN107773555A CN201711017618.9A CN201711017618A CN107773555A CN 107773555 A CN107773555 A CN 107773555A CN 201711017618 A CN201711017618 A CN 201711017618A CN 107773555 A CN107773555 A CN 107773555A
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
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Abstract
The invention belongs to pharmaceutical technology field, the nifedipine micropore permeation pump particulate of specifically a kind of particle containing polyoxyethylene as expansion capsule core and preparation method thereof.Micropore permeation pump particulate is to be used as expansion capsule core using polyoxyethylene particle.Nifedipine micropore permeation pump particulate prepared by the present invention is released the drug with approximate zero order release rate, simple production process, is easy to industrialization amplification.
Description
Technical field
The invention belongs to pharmaceutical technology field, nitre benzene of specifically a kind of particle containing polyoxyethylene as expansion capsule core
Horizon micropore permeation pump particulate and preparation method thereof.
Background technology
Nifedipine (Nifedipine), chemical name：1,4- dihydro -2,6- dimethyl -4- (2- nitrobenzophenones) -3,5-
Pyridinedicarboxylic acid dimethyl ester, it is one kind in calcium ion antagonist, is the choice drug of ariant angina, clinic is applied to pre-
Anti- and treatment coronary disease and angina pectoris, suitable for various types of hypertension, also has good therapeutic effect to intractable, severe hypertension.
Hypertension is one of most common angiocardiopathy in the world today, and cardiovascular and cerebrovascular disease main hazard because
Element.China's Prevalence of Hypertension is about 12%, and existing hyperpietic's number is more than 100,000,000 people, and every year with the speed more than 3,000,000 people
Degree increases.Antihypertensive medicine is currently used in be broadly divided into diuretics, beta-blocker, calcium ion antagonist, act on kidney
Several major classes such as element-hypertensin system medicine, sympatholytic agent.Wherein, calcium ion antagonist is as anti-hypertension one
The status of line drug substance stable, affirmed in 2003 European hypertension prevention and control guides.
Nifedipine ordinary tablet need to taken three times per day, it is impossible to preferably maintain the stabilization of internal blood concentration and daily blood pressure
Steadily.At present, Nifedipine sustained release tablets and controlled release tablet, wherein daily controlled release preparation once is given birth to by Bayer A.G
Production, is 24 hours controlled release preparations close to constant release, and nifedipine and 24 hours keep basically identical rate of release, its body
The correlation of outer release profiles does not decline to a great extent in drug release later stage rate of release up to 0.99, keeps constant speed to release with many 16h
The controlled release preparation put maintains more stable state compared to there is certain advantage per blood pressure in the daytime.
Oral osmotic pump controlled-releasing tablet (OPT) is optimal controlled release formulations for oral administration so far, and it is using osmotic pressure as driving
Power, medicine is set to reach Zero order release.Its advantage has：Extend administration time, reduce administration number of times, reduce adverse reaction frequency
And degree；Releasing the drug, it is small to be influenceed by internal condition such as PH, gastrointestinal motility and food etc., and In vitro-in vivo correlation is preferable, greatly carries
High Drug safety and validity.
According to its design feature, Oros can be divided into elementary osmotic pump and (the also known as push-pull infiltration of more chamber osmotic pumps
Pump) two classes.Wherein elementary osmotic pump piece is the first generation product of osmotic pump controlled release tablet, and the medicine for being only applicable to dissolve in water is (logical
Normal solubility is 5-30g/100ml), label includes medicine and penetrating agent, the pellicle of one layer of controlled release of outsourcing, is then existed with laser
A small delivery aperture is opened on label coating membrane, the moisture in oral rear intestines and stomach enters label by pellicle, forms medicine
Saturated solution or suspension, the dissolving of Thief zone auxiliary material, makes big permeable pressure head inside and outside film be present, by decoction with constant speed in addition
Rate extrudes release hole, and its discharge is equal with penetrating into the water in film, until label medicine is molten most.More chamber osmotic pumps are main
Suitable for being insoluble in water or having the medicine of incompatibility.Its label is made up of double-deck or three-layer tablet.In label by medicine, have
The hydrophilic polymer of osmotic pressure activity and one layer of other auxiliary materials composition are medicated layer；Other one layer of label is gathered by hydrophily
Compound, osmotic pressure accelerator and other auxiliary materials composition, are properly termed as boosting layer.Pellicle is surrounded by outside label, and in pellicle
Both sides it is unilateral on open one or several release holes, medicine is connected by release hole with external environment.When osmotic pump tablet enter it is water-based
During environment, moisture enters label by release hole and pellicle, and medicine is partly dissolved or is suspended in the presence of permeation enhancers
In water, discharged in the presence of osmotic pressure from small delivery aperture, meanwhile, volume is swollen after the hydrophilic polymer water suction in boosting layer
It is swollen, certain impetus is produced from release hole release to medicine.
Nifedipine controlled-release tablet 24 hours is close to constant release, but preparation technology is complicated, first has to suppress double-layer tablets, then
Pellicle is wrapped up, then carries out laser boring, the requirement to equipment is very high.
Chinese invention patent CN105920000A (publication number) discloses " the nitre benzene of the global pharmaceutical discovery in Chinese medicines group Guangdong
Ground release preparation and preparation method thereof ".It is directed to nifedipine being prepared into drug containing with pharmaceutically acceptable auxiliary material and delays
Release capsule core and drug containing release layer.From the point of view of drug-eluting curve, test sample is in different condition medium, 5~6h cumulative release
Amount just reaches more than 80%.Slow-release time can only achieve more than 6 hours.
Open " the nifedipines for having invented Shenyang Pharmaceutical University's invention of Chinese invention patent CN102429874A (publication number)
Matrix type sustained release pellet and its preparation method and application ".It is directed to nifedipine liquid being co-mulled and made into thing and relevant auxiliary materials system
It is standby into matrix sustained-release pellets.From the point of view of drug-eluting curve, test sample reaches 40% in 2h or so releases, reaches within 8 hours or so
50%, the release of medicine later stage is short of power, and shows to discharge incomplete trend.This is also that insoluble drug is prepared into matrix type
The place of sustained-release preparation deficiency.
Multiple-unit microparticulate systems (MUPS) have more advantages than only metasystem, and multiple-unit can be very good to be distributed to stomach
In enteron aisle, bioavilability can be improved, it is possible to reduce topical remedy's concentration, reduce drug toxicity danger and side effect
(G.M.Clarke,J.M.Newton,M.D.Short,Comparative gastrointestinal transit of
Pellet system of varying density, Int.J.Pharm.114 (1995) 1-11), reduce individual internal or individual
External bioavilability difference (J.P.Decheshe, L.Delattre, A new enteric tablet of
acetylsalicylic acid:biopharmaceutical aspects,Int.J.Pharm.34(1996)257–262)。
Thus urgent need one kind, which can reach 12 hours slow release and cans, makes nifedipine discharge complete multiple-unit microparticle formulation.
The content of the invention
It is an object of the invention to provide a kind of nifedipine micropore permeation pump particulate and preparation method thereof.
To achieve the above object, the present invention use technical scheme for：
A kind of nifedipine micropore permeation pump particulate, it is characterised in that:Micropore permeation pump particulate is with polyoxyethylene particle
As expansion capsule core.
Micropore permeation pump particulate is followed successively by polyoxyethylene particle expansion capsule core, nifedipine medicated layer and semi-transparent from the inside to the outside
Film, each component mass ratio are oxygen ethene particle：Nifedipine medicated layer：Pellicle=(10~40)：(15~75)：(5~50).
Wherein, to be 600000~7000000 selected from molecular weight, preferred molecular weight is the polyoxyethylene particle
1000000~7000000 scope, more preferably molecular weight are 4000000~7000000 scope；Particle diameter is selected from 50 μm~400
μm, preferably 100 μm~400 μm, more preferably 150~350 μm.
The nifedipine medicated layer is made up of nifedipine, adhesive, osmotic pressure regulator, filler；Each component weight
Amount ratio is nifedipine：Adhesive：Osmotic pressure regulator：Filler=(10~90)：(1~15)：(1~25)：(0~
30)。
One or more of the described adhesive in hydroxypropyl methylcellulose, hydroxypropyl cellulose, PVP；The infiltration
Press conditioning agent be selected from sucrose, lactose, glucose, mannitol, sorbierite, fructose, sodium chloride, potassium chloride, sodium sulphate, sodium phosphate,
One or more in sodium dihydrogen phosphate；The filler is selected from microcrystalline cellulose, starch and its derivative, cyclodextrin, sweet dew
One or more in alcohol, lactose, sucrose.
The pellicle is made up of cellulose, plasticizer, pore-foaming agent；Each component part by weight is cellulose：Plasticizer：Cause
Hole agent=(10~50)：(1~15)：(1~25).
The cellulose is selected from cellulose acetate or ethyl cellulose；The plasticizer is selected from glycerine, propane diols, poly- second two
One or more in alcohol, triethyl citrate, diethyl phthalate, glyceric acid triethyl, castor oil；The pore-foaming agent
One or more in sucrose, lactose, mannitol, polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, PVP.
A kind of preparation method of nifedipine micropore permeation pump particulate：
A) the suitable polyoxyethylene particle of particle diameter is screened as expansion capsule core；
B) nifedipine and adhesive, osmotic pressure regulator, filler are configured to ethanol suspension and spray to polyoxy second
Alkene particle expansion capsule core surface prepares nifedipine drug containing particulate；
C) plasticizer, pore-foaming agent and cellulose are dissolved in into organic solvent-aqueous solution to wrap nifedipine medicine-containing particle
Clothing, nifedipine micropore permeation pump particulate is made.
The obtained nifedipine micropore permeation pump particulate is inserted capsule in the way of formulation art is conventional or is pressed into
Tablet.
Advantages of the present invention：
Polyoxyethylene particle is prepared nifedipine micropore permeation pump particulate by the present invention, by nifedipine
Drug suspension is sprayed on polyoxyethylene particle, then wraps up pellicle as oral formulations.After oral said preparation, moisture leads to
Pore-foaming agent on semi-permeable membrane enters medicine layer, and medicine layer forms suspension, portion in the presence of the auxiliary material such as moisture and penetrating agent
Drug suspension is divided to be discharged by micropore, when moisture penetration medicine layer contacts expansion capsule core, it is swollen that polyoxyethylene meets water
It is swollen, promote remaining drug suspension to discharge, active medicine nitre benzene can be discharged with the rate of releasing drug of approximately constant
It is flat.
The characteristics of nifedipine micropore permeation pump particulate of the present invention combines multiple-unit microparticulate systems and osmotic pumps, can
Active medicine nifedipine is discharged with the speed of approximately constant, and not by media environment pH value, gastrointestinal peristalsis and food etc.
The influence of factor, there is preferable In vitro-in vivo correlation, blood concentration fluctuation caused by common oral preparation can be avoided, reduce clothes
Medicine number, Drug safety, validity and compliance is greatly improved.The preparation process of the present invention is simple, only need to sieve polyoxy
Ethene particle, the medicine-feeding of nifedipine suspension, semi-transparent film coating three step process, it is not necessary to which Double layer pellet and laser boring etc. are cumbersome
Technique and costliness equipment.After oral said preparation, moisture enters medicine layer by the pore-foaming agent on pellicle, and medicine layer is in water
Point and the auxiliary material such as penetrating agent in the presence of form suspension, some drugs suspension can be discharged by micropore, work as moisture
Medicine layer contact expansion capsule core is penetrated, polyoxyethylene water-swellable, promotes remaining drug suspension to discharge.The present invention is
The conventional technology of preparation, easy industrialization.
Brief description of the drawings
Fig. 1 is nifedipine micropore permeation pump of the particle containing polyoxyethylene provided in an embodiment of the present invention as expansion capsule core
Particulate schematic diagram.
Fig. 2 obtains preparation for each embodiment provided in an embodiment of the present invention and existed with commercial preparation nifedipine Adalat-L
900mL0.25%SDS, pH are the drug release patterns figure in 6.8 dissolution medium.
Embodiment
Following examples are that the present invention is further described, without limiting the scope of the present invention.
Invention formulation can discharge nifedipine with the rate of releasing drug of approximately constant.Mainly have polyoxyethylene particle,
Nifedipine medicated layer and pellicle are formed, wherein nifedipine medicated layer by nifedipine, adhesive, osmotic pressure regulator,
Filler and other pharmaceutic adjuvants composition；Pellicle is made up of cellulose acetate or ethyl cellulose, plasticizer, pore-foaming agent.This
The prepared nifedipine micropore permeation pump particulate of invention is released the drug with approximate zero order release rate, simple production process, is easy to produce
Industryization is amplified.
Embodiment 1
Prescription
Preparation technology：
1st, the preparation containing pill：
The polyoxyethylene coagulant particle 300g of 150~250 μm of particle diameter are screened, are placed in DPP-II fluidized bed granulation bags
In clothing machine；Nifedipine, hydroxypropyl methylcellulose E5, sodium chloride, the lactose of recipe quantity are weighed, is distributed in 95% ethanol, point
Dissipate uniform.Open (the m of the fluid bed blow rate required 15 ± 23/ h)/kg, 1.5 ± 0.2bar of atomizing pressure, hydrojet 15 ± 1g/min of speed,
50 ± 2 DEG C of EAT, 30 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue to dry in fluid bed, obtain nifedipine and contain
Pill.
2nd, semi-transparent film coating
The cellulose acetate, Macrogol 4000, hydroxypropyl methylcellulose E5 for weighing recipe quantity are dissolved in acetone-water solution,
After the completion of dissolving, above-mentioned nifedipine is placed in DPP-II fluidized bed granulation seed-coating machines containing pill, lysate is sprayed onto nitre benzene
Horizon surface containing pill, fluid bed impose a condition to open (the m of the fluid bed blow rate required 18 ± 23/ h)/kg, atomizing pressure 1.6 ±
0.2bar, hydrojet 20 ± 1g/min of speed, 45 ± 2 DEG C of EAT, 28 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue flowing
Change in bed and dry, obtain nifedipine micropore permeation pump particulate.
3rd, capsule is filled
Capsule is filled according to every capsule nifedipine labelled amount 20mg (referring to Fig. 1).
Embodiment 2
Prescription
Preparation technology：
1st, the preparation containing pill：
The particle 300g of polyoxyethylene 303 of 150~250 μm of particle diameter is screened, is placed in DPP-II fluidized bed granulation seed-coating machines；
Recipe quantity nifedipine, hydroxypropyl cellulose LF, potassium chloride, mannitol are weighed, is distributed in 95% ethanol, is uniformly dispersed.
Open (the m of the fluid bed blow rate required 15 ± 23/ h)/kg, 1.5 ± 0.2bar of atomizing pressure, hydrojet 14 ± 1g/min of speed, enter wind-warm syndrome
50 ± 2 DEG C of degree, 30 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue to dry in fluid bed, obtain nifedipine and contain pill.
2nd, semi-transparent film coating
The cellulose acetate, triethyl citrate, hydroxypropyl cellulose LF for weighing recipe quantity are dissolved in acetone-water solution,
After the completion of dissolving, above-mentioned nifedipine is placed in DPP-II fluidized bed granulation seed-coating machines containing pill, lysate is sprayed onto nitre benzene
Horizon surface containing pill, fluid bed impose a condition to open (the m of the fluid bed blow rate required 18 ± 23/ h)/kg, atomizing pressure 1.6 ±
0.2bar, hydrojet 20 ± 1g/min of speed, 45 ± 2 DEG C of EAT, 28 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue flowing
Change in bed and dry, obtain nifedipine micropore permeation pump particulate.
3rd, capsule is filled
Capsule is filled according to every capsule nifedipine labelled amount 20mg.
Embodiment 3
Prescription
Preparation technology：
1st, the preparation containing pill：
The particle 300g of polyoxyethylene 303 of 150~250 μm of particle diameter is screened, is placed in DPP-II fluidized bed granulation seed-coating machines；
Recipe quantity nifedipine, hydroxypropyl methylcellulose E5, sodium chloride, lactose are weighed, is distributed in 95% ethanol, is uniformly dispersed.Open
Open (the m of the fluid bed blow rate required 16 ± 23/ h)/kg, 1.6 ± 0.2bar of atomizing pressure, hydrojet 18 ± 1g/min of speed, EAT
50 ± 2 DEG C, 30 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue to dry in fluid bed, obtain nifedipine and contain pill.
2nd, semi-transparent film coating
The ethyl cellulose, polyethylene glycol, hydroxypropyl methylcellulose E5 for weighing recipe quantity are dissolved in acetone-water solution, dissolving
After the completion of, above-mentioned nifedipine is placed in DPP-II fluidized bed granulation seed-coating machines containing pill, lysate is sprayed onto nifedipine
Surface containing pill, fluid bed impose a condition to open (the m of the fluid bed blow rate required 18 ± 23/ h)/kg, atomizing pressure 1.6 ±
0.2bar, hydrojet 20 ± 1g/min of speed, 50 ± 2 DEG C of EAT, 35 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue flowing
Change in bed and dry, obtain nifedipine micropore permeation pump particulate.
3rd, capsule is filled
Capsule is filled according to every capsule nifedipine labelled amount 20mg.
Embodiment 4
Prescription
Preparation technology：
1st, the preparation containing pill：
The polyoxyethylene Coagulant particle 300g of 150~250 μm of particle diameter are screened, are placed in DPP-II fluidized bed granulation bags
In clothing machine；Recipe quantity nifedipine, hydroxypropyl methylcellulose E5, sodium chloride, lactose are weighed, is distributed in 95% ethanol, is disperseed
Uniformly.Open (the m of the fluid bed blow rate required 15 ± 23/ h)/kg, 1.5 ± 0.2bar of atomizing pressure, hydrojet 14 ± 1g/min of speed, enter
50 ± 2 DEG C of air temperature, 30 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue to dry in fluid bed, obtain nifedipine drug containing
Ball.
2nd, semi-transparent film coating
The cellulose acetate, polyethylene glycol, hydroxypropyl methylcellulose E5 for weighing recipe quantity are dissolved in acetone-water solution, dissolving
After the completion of, above-mentioned nifedipine is placed in DPP-II fluidized bed granulation seed-coating machines containing pill, lysate is sprayed onto nifedipine
Surface containing pill, fluid bed impose a condition to open (the m of the fluid bed blow rate required 18 ± 23/ h)/kg, atomizing pressure 1.6 ±
0.2bar, hydrojet 25 ± 1g/min of speed, 50 ± 2 DEG C of EAT, 35 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue flowing
Change in bed and dry, obtain nifedipine micropore permeation pump particulate.
3rd, tabletting
Nifedipine micropore permeation pump particulate is mixed with appropriate filler, pressed according to every nifedipine labelled amount 20mg
Piece.
Embodiment 5
Prescription
1st, the preparation containing pill：
The polyoxyethylene Coagulant particle 300g of 100~200 μm of particle diameter are screened, are placed in DPL-3/5 fluidized bed granulation bags
In clothing machine；Recipe quantity nifedipine, hydroxypropyl methylcellulose E5, sodium chloride, lactose are weighed, is distributed in 95% ethanol, is disperseed
Uniformly.Open (the m of the fluid bed blow rate required 26~35 ± 23/ h)/kg, 2.0 ± 0.2bar of atomizing pressure, 52 ± 1g/ of hydrojet speed
Min, 50 ± 2 DEG C of EAT, 30 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue to dry in fluid bed, with obtaining nitre benzene
It is flat to contain pill.
2nd, semi-transparent film coating
The cellulose acetate, polyethylene glycol, hydroxypropyl methylcellulose E5 for weighing recipe quantity are dissolved in acetone-water solution, dissolving
After the completion of, above-mentioned nifedipine is placed in DPL-3/5 fluidized bed granulation seed-coating machines containing pill, lysate is sprayed onto nifedipine
Surface containing pill, fluid bed impose a condition to open (the m of the fluid bed blow rate required 36 ± 23/ h)/kg, atomizing pressure 2.0 ±
0.2bar, hydrojet 57 ± 1g/min of speed, 46 ± 2 DEG C of EAT, 28 ± 2 DEG C of temperature of charge, after hydrojet terminates, continue flowing
Change in bed and dry, obtain nifedipine micropore permeation pump particulate.
3rd, capsule is filled
Capsule is filled according to every capsule nifedipine labelled amount 20mg.
Embodiment 6
Dissolution determination
Lucifuge operates, and takes above-described embodiment to obtain each formulation samples, by dissolution rate and drug release determination method (2015 editions pharmacopeia
The method of general rule 0,931 first), with 900mL0.25%SDS, pH is 6.8 dissolution medium, and temperature (37 ± 0.5) DEG C rotating speed is 100r/
Min, take nifedipine sample (n=6), a piece of/grain placed in each dissolution basket, respectively 0.5,1,2,3,4,5,6,7,8,9,
10th, 11,12h samplings 5mL, per sub-sampling after supplement 5mL dissolution mediums simultaneously at once.The sample of taking-up is micro- by 0.45 μm of water system
Hole membrane filtration, takes subsequent filtrate.Simultaneously control, chromatographic condition are used as using marketed drugs：Octadecylsilane chemically bonded silica is to fill out
Agent is filled, adds guard column, mobile phase：Acetonitrile：0.3% triethylamine (60:40, v/v), Detection wavelength：265nm, flow velocity 0.8mL
min-1, sample size：20μL.Calculate the Accumulation dissolution of each sample.
Accumulation dissolution calculation formula：
Xi schools=Xi+ (X1+X2+......+Xi) V2/V1
V1 is dissolution medium cumulative volume, and for V2 to supplement volume after every sub-sampling, Xi is the actually measured percentage of ith
Dissolution rate.
From above-mentioned table 1 and Fig. 2, the nifedipine micropore permeation pump particulate by the use of polyoxyethylene particle as expansion capsule core
Compared with former triturate, rate of release is slower, and can reach complete release.
Claims (8)
- A kind of 1. nifedipine micropore permeation pump particulate, it is characterised in that:Micropore permeation pump particulate is to be made with polyoxyethylene particle To expand capsule core.
- 2. the nifedipine micropore permeation pump particulate as described in claim 1, it is characterised in that:Micropore permeation pump particulate by it is interior extremely Polyoxyethylene particle expansion capsule core, nifedipine medicated layer and pellicle are followed successively by outside, each component mass ratio is oxygen ethene particle： Nifedipine medicated layer：Pellicle=(10~40)：(15~75)：(5~50).
- 3. the nifedipine micropore permeation pump particulate as described in claim 1 or 2, it is characterised in that：The polyoxyethylene particle To be 600000~7000000 selected from molecular weight, preferred molecular weight is 1000000~7000000 scope, more preferably molecular weight For 4000000~7000000 scope；Particle diameter is selected from 50 μm~400 μm, preferably 100 μm~400 μm, more preferably 150~350 μ m。
- 4. the nifedipine micropore permeation pump particulate as described in claim 2, it is characterised in that：The nifedipine medicated layer is by nitre Benzene Horizon, adhesive, osmotic pressure regulator, filler composition；Each component part by weight is nifedipine：Adhesive：Osmotic pressure Conditioning agent：Filler=(10~90)：(1~15)：(1~25)：(0~30).
- 5. the nifedipine micropore permeation pump particulate as described in claim 4, it is characterised in that：It is fine that described adhesive is selected from hydroxypropyl first Tie up the one or more in element, hydroxypropyl cellulose, PVP；The osmotic pressure regulator be selected from sucrose, lactose, glucose, One or more in mannitol, sorbierite, fructose, sodium chloride, potassium chloride, sodium sulphate, sodium phosphate, sodium dihydrogen phosphate；It is described One or more of the filler in microcrystalline cellulose, starch and its derivative, cyclodextrin, mannitol, lactose, sucrose.
- 6. the nifedipine micropore permeation pump particulate as described in claim 2, it is characterised in that：The pellicle is by cellulose, increasing Mould agent, pore-foaming agent is formed；Each component part by weight is cellulose：Plasticizer：Pore-foaming agent=(10~50)：(1~15)：(1~ 25)。
- 7. the nifedipine micropore permeation pump particulate as described in claim 6, it is characterised in that：The cellulose is selected from acetate fiber Element or ethyl cellulose；The plasticizer is selected from glycerine, propane diols, polyethylene glycol, triethyl citrate, phthalic acid diethyl One or more in ester, glyceric acid triethyl, castor oil；The pore-foaming agent be selected from sucrose, lactose, mannitol, polyethylene glycol, One or more in hydroxypropyl methylcellulose, hydroxypropyl cellulose, PVP.
- A kind of 8. preparation method of nifedipine micropore permeation pump particulate described in claim 1, it is characterised in that：A) the suitable polyoxyethylene particle of particle diameter is screened as expansion capsule core；B) nifedipine and adhesive, osmotic pressure regulator, filler are configured to ethanol suspension and spray to polyoxyethylene Grain expansion capsule core surface prepares nifedipine drug containing particulate；C) plasticizer, pore-foaming agent and cellulose are dissolved in into organic solvent-aqueous solution to be coated nifedipine medicine-containing particle, made Obtain nifedipine micropore permeation pump particulate.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711017618.9A CN107773555A (en) | 2017-10-26 | 2017-10-26 | A kind of nifedipine micropore permeation pump particulate and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711017618.9A CN107773555A (en) | 2017-10-26 | 2017-10-26 | A kind of nifedipine micropore permeation pump particulate and preparation method thereof |
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| CN107773555A true CN107773555A (en) | 2018-03-09 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111184699A (en) * | 2020-04-09 | 2020-05-22 | 河北大学 | Nifedipine controlled release capsule and preparation method thereof |
| CN117084992A (en) * | 2023-10-19 | 2023-11-21 | 华润双鹤利民药业（济南）有限公司 | Nifedipine controlled release tablet preparation and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102138912A (en) * | 2010-12-03 | 2011-08-03 | 中国药科大学 | Nifedipine osmotic pump controlled release tablet and preparation method thereof |
| US8637080B2 (en) * | 2007-06-28 | 2014-01-28 | Osmotica Kereskedelmi és Szolgáltató, KFT | Rupturing controlled release device comprising a subcoat |
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2017
- 2017-10-26 CN CN201711017618.9A patent/CN107773555A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8637080B2 (en) * | 2007-06-28 | 2014-01-28 | Osmotica Kereskedelmi és Szolgáltató, KFT | Rupturing controlled release device comprising a subcoat |
| CN102138912A (en) * | 2010-12-03 | 2011-08-03 | 中国药科大学 | Nifedipine osmotic pump controlled release tablet and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111184699A (en) * | 2020-04-09 | 2020-05-22 | 河北大学 | Nifedipine controlled release capsule and preparation method thereof |
| CN117084992A (en) * | 2023-10-19 | 2023-11-21 | 华润双鹤利民药业（济南）有限公司 | Nifedipine controlled release tablet preparation and preparation method thereof |
| CN117084992B (en) * | 2023-10-19 | 2023-12-26 | 华润双鹤利民药业（济南）有限公司 | Nifedipine controlled release tablet preparation and preparation method thereof |
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Application publication date: 20180309 |