CN105412040B - A kind of Nifedipine controlled-release tablet and preparation method thereof - Google Patents
A kind of Nifedipine controlled-release tablet and preparation method thereof Download PDFInfo
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- CN105412040B CN105412040B CN201510924330.4A CN201510924330A CN105412040B CN 105412040 B CN105412040 B CN 105412040B CN 201510924330 A CN201510924330 A CN 201510924330A CN 105412040 B CN105412040 B CN 105412040B
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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
- A61K9/20—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
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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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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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
- A61K9/20—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
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
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Abstract
The present invention provides a kind of Nifedipine controlled-release tablet, including label and the coating that is wrapped on the label；The label includes medicated layer and the boosting layer that is compounded in medicated layer, and the coating has release hole in the side of medicated layer；The medicated layer includes following components, in terms of the mass percent for accounting for medicated layer total weight：Nifedipine：5~45%；Suspending agent：25~85%；Penetrating agent：1~25%；Lubricant：0.5~10%；The boosting layer includes following components, in terms of the mass percent for accounting for boosting layer total weight：Promote osmopolymer：45~90%；Penetrating agent：5~45%；Colorant：0.1~4%；Lubricant：0.1~10%；Described includes filmogen and pore-foaming agent, and the filmogen is 100 with pore-foaming agent mass ratio：(5~30).The Nifedipine controlled-release tablet composition of the present invention is simple, and controlled-release effect is good.The present invention provides a kind of preparation method of Nifedipine controlled-release tablet.
Description
Technical field
The invention belongs to technical field of medicine more particularly to a kind of Nifedipine controlled-release tablet and preparation method thereof.
Background technology
Nifedipine develops listing for the first time by Bayer A.G in the seventies, through for many years clinical application and deeply grind
Study carefully, nifedipine has become one of current clinical treatment hypertension and anginal choice drug.Nifedipine has very strong
Light sensitivity, light-exposed intramolecular will produce disproportionated reaction and generates nitro or nitrosobenzene pyridine derivate.Nifedipine is commonly made
Agent causes increased heart rate, activates stomodaeal nervous system, is unfavorable for the control etc. to myocardial ischemia and heart failure with having reflectivity
Adverse reaction, and frequent drug administration is needed, the medication demand for causing it to be difficult to meet patient.Therefore, nifedipine ordinary preparation
It has been phased out in the world instead long-acting slow, the controlled release preparation product of nifedipine.
A variety of controlled release agent types of nifedipine are developed both at home and abroad at present, commercially available nifedipine delays controlled release
Product is broadly divided into Nifedipine sustained release tablets I (such as Dezhou pharmacy trade name Nifedipine) and II (such as Qingdao of Nifedipine sustained release tablets
Huanghai Sea pharmacy trade name we Fuda).Compared with nifedipine ordinary preparation, the medicine of nifedipine I and nifedipine II is for power
Performance has improvement, and half-life period (tl/2) opposite extension, blood concentration stationarity is opposite to be improved, and peak valley phenomenon is reduced,
Daily medicining times are kept to 2 times by 3 times.But the drug therapy away from current International Medical bound pair hypertension is advocated (to use long-acting
Antihypertensive drugs, i.e., the 1 day drug that need to only take 1 time are reaching steady decompression with this, are reducing fluctuation of blood pressure, effectively control blood for 24 hours
Pressure) there is a distance.
Nifedipine osmotic pump tablet is one of foremost product in osmotic pumps, and said preparation belongs to push-pull osmotic pump piece,
Which overcome the deficiency of the common sustained release tablets of nifedipine, drug 24 hours Zero order releases in vivo reduce internal blood concentration
Peak valley phenomenon, the characteristics of it is administered one day once also improves the compliance of patient's medication.
But these osmotic pump preparations in medicated layer in addition to penetrating agent, promote the functional auxiliary materials such as osmopolymer other than, also
Other materials can be added to regulate and control drug release behavior, such as 101869555 A of patent CN are added in boosting layer and remove functional auxiliary material
Outside polyoxyethylene, it is additionally added diluent hydroxypropyl methylcellulose；Although new auxiliary material has been used to replace polyoxyethylene in some research,
But it in order to reach polyoxyethylated effect, needs to use two or more auxiliary material mixture, these excessive auxiliary materials
So that preparation process is excessively complicated, its industrialization production is hindered.
Invention content
The purpose of the present invention is to provide a kind of Nifedipine controlled-release tablet and preparation method thereof, nitre benzene provided by the invention
Flat controlled release tablet composition is simple and easy to get, is easy to industrialized production.
The present invention provides a kind of Nifedipine controlled-release tablet, including label and the coating that is wrapped on the label；
The label includes medicated layer and the boosting layer that is compounded in medicated layer, and the coating is arranged in the side of medicated layer
There is release hole；
The medicated layer includes following components, in terms of the mass percent for accounting for medicated layer total weight：
Nifedipine：5~45%；
Suspending agent：25%~85%；
Penetrating agent：1~25%；
Lubricant：0.5~10%；
The boosting layer includes following components, in terms of the mass percent for accounting for boosting layer total weight：
Promote osmopolymer：45~90%；
Penetrating agent：5~45%；
Colorant：0.1~4%；
Lubricant：0.1~10%；
Described includes filmogen and pore-foaming agent, and the mass ratio of the filmogen and pore-foaming agent is 100：(5~
30)。
Preferably, the nifedipine is nifedipine micro mist；
The grain size of the nifedipine micro mist is 10~30 μm.
Preferably, in the medicated layer, the suspending agent includes the polyoxyethylene that molecular weight is 10~900,000；
The penetrating agent includes one or more of sodium chloride, sucrose and mannitol；
The lubricant includes the one or more of stearic acid, magnesium stearate, talcum powder, superfine silica gel powder.
Preferably, the suspending agent accounts for the 10~40% of the medicated layer total weight；
The penetrating agent accounts for the 35~80% of the medicated layer total weight；
The lubricant accounts for the 2~20% of the medicated layer total weight.
Preferably, in the boosting layer, the osmopolymer that promotees includes the polyoxy second that molecular weight is 400~7,000,000
Alkene；
The penetrating agent includes one or more of sodium chloride, sucrose and mannitol；
The colorant includes iron oxide red, iron oxide yellow, iron oxide purple or iron oxide black；
The lubricant includes the one or more of stearic acid, magnesium stearate, talcum powder, superfine silica gel powder.
Preferably, the rush osmopolymer accounts for the 50~85% of the boosting layer total weight；
The penetrating agent accounts for the 10~40% of the boosting layer total weight；
The colorant accounts for the 0.2~3% of the boosting layer total weight；
The lubricant accounts for the 0.5~8% of the boosting layer total weight.
Preferably, the mass ratio of the medicated layer and the boosting layer is 1：(0.4~2.0).
Preferably, the coating weight gain is 8~17%.
Preferably, the Nifedipine controlled-release tablet further includes the light shield layer being wrapped in the coating.
The present invention provides a kind of preparation method of Nifedipine Tablets, includes the following steps：
A) by 5~45% nifedipine, 25%~85% suspending agent, 1~25% penetrating agent and 0.5~10%
Mix lubricant obtains medicated layer material；
By 45~90% rush osmopolymer, 5~45% penetrating agent, 0.1~4% colorant and 0.1~10%
Mix lubricant, obtain boosting layer material；
B) by the step A) in medicated layer material and boosting layer material carry out tabletting, obtain double-deck core；
C) using coating solution to the step B) obtained double-deck core is coated, coating tablet is obtained,
The coating solution includes filmogen, pore-foaming agent and solvent, and the mass ratio of the filmogen and pore-foaming agent is
100：(5~30)；
D) by the step C) in coating tablet medicated layer a side perforating, obtain Nifedipine controlled-release tablet.
The present invention provides a kind of Nifedipine controlled-release tablet, including label and the coating that is wrapped on the label；It is described
Label includes medicated layer and the boosting layer that is compounded in medicated layer, and the coating is provided with release hole in the side of medicated layer；Institute
It includes following components to state medicated layer, in terms of the mass percent for accounting for medicated layer total weight：Nifedipine：5~45%；Suspending agent：
25%~85%；Penetrating agent：1~25%；Lubricant：0.5~10%；The boosting layer includes following components, to account for boosting layer
The mass percent meter of total weight：Promote osmopolymer：45~90%；Penetrating agent：5~45%；Colorant：0.1~4%；Profit
Lubrication prescription：0.1~10%；Described includes filmogen and pore-foaming agent, and the mass ratio of the filmogen and pore-foaming agent is
100：(5~30).Nifedipine controlled-release tablet provided by the invention is not necessarily to by limiting penetrating agent and promoting the ratio of osmopolymer
The other slow-release materials of addition, can reach preferable slow release effect, and raw material composition is simple and easy to get, is convenient for industrialization production.It is real
Test the result shows that, Nifedipine controlled-release tablet in the present invention zero-order release in 0~20 hour, rate of releasing drug 1.3 ±
0.3mg/h, accumulative releasing degree reaches 90% or more within 24 hours.
Description of the drawings
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technology description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
The embodiment of invention for those of ordinary skill in the art without creative efforts, can also basis
The attached drawing of offer obtains other attached drawings.
Fig. 1 is the drug release profiles of the Nifedipine controlled-release tablet in the embodiment of the present invention 1；
Fig. 2 is the drug release profiles of the Nifedipine controlled-release tablet in the embodiment of the present invention 2；
Fig. 3 is the drug release profiles of the Nifedipine controlled-release tablet in the embodiment of the present invention 3；
Fig. 4 is the drug release profiles of the embodiment of the present invention 3 and the Nifedipine controlled-release tablet in comparative example 1；
Fig. 5 is the drug release profiles of the embodiment of the present invention 1 and the Nifedipine controlled-release tablet in comparative example 2；
Fig. 6 is the drug release profiles of the embodiment of the present invention 2 and the Nifedipine controlled-release tablet in comparative example 3；
Fig. 7 is the drug release profiles of the embodiment of the present invention 1 and the Nifedipine controlled-release tablet in comparative example 4.
Specific implementation mode
The present invention provides a kind of Nifedipine controlled-release tablet, including label and the coating that is wrapped on the label；
The label includes medicated layer and the boosting layer that is compounded in medicated layer, and the coating is arranged in the side of medicated layer
There is release hole；
The medicated layer includes following components, in terms of the mass percent for accounting for medicated layer total weight：
Nifedipine：5~45%；
Suspending agent：25%~85%；
Penetrating agent：1~25%；
Lubricant：0.5~10%；
The boosting layer includes following components, in terms of the mass percent for accounting for boosting layer total weight：
Promote osmopolymer：45~90%；
Penetrating agent：5~45%；
Colorant：0.1~4%；
Lubricant：0.1~10%；
Described includes filmogen and pore-foaming agent, and the mass ratio of the filmogen and pore-foaming agent is 100：(5~
30)。
Without additional addition slow-release material in Nifedipine controlled-release tablet provided by the invention, it will be able to realize preferable controlled release
Effect.
In the present invention, the label of the Nifedipine controlled-release tablet is preferably double-deck core, and one layer is medicated layer, another layer
Hardness for boosting layer, the label is preferably 4~6kg/mm2, more preferably 4.5~5.5kg/mm2, the medicated layer and help
The mass ratio for pushing away layer is preferably 1：(0.4~2), more preferably 1：(0.45~1.5), most preferably 1：(0.5~0.8), specifically
, can be 1 in an embodiment of the present invention：0.55、1:0.67 or 1:0.56.
In the present invention, in the medicated layer, nifedipine accounts for the 5~45% of the medicated layer total weight, preferably
10~40%, more preferably 15~35%, most preferably 20~30%, specifically, in an embodiment of the present invention, Ke Yishi
21%, 23.2% or 20.4%；Present invention preferably employs nifedipine micro mist, the grain size of the nifedipine micro mist is preferably 10
~30 μm, more preferably 15~25 μm.
In the medicated layer, suspending agent preferably includes the polyoxyethylene that molecular weight is 10~900,000, more preferably molecule
The polyoxyethylene that amount is 100,000,300,000,600,000 or 900,000；The suspending agent accounts for the 25~85% of medicated layer total weight, preferably
35~80%, more preferably 45~75%, most preferably 60~72%, specifically, in an embodiment of the present invention, Ke Yishi
71%, 70.4% or 71.2%.
In the medicated layer, penetrating agent preferably includes one or more of sodium chloride, sucrose and mannitol；The rush
Penetration enhancer accounts for the 1~25% of medicated layer total weight, preferably 2~20%, more preferably 3~15%, most preferably 4~10%, tool
Body, can be 5%, 3.9% or 6.2% in an embodiment of the present invention.
In the medicated layer, lubricant preferably include stearic acid, magnesium stearate, talcum powder, superfine silica gel powder one kind or
It is several；The lubricant accounts for the 0.5~10% of medicated layer total weight, preferably 1~8%, more preferably 2~5%, most preferably
2.2% or 2.5%.
In the boosting layer, the osmopolymer that promotees preferably includes the polyoxyethylene that molecular weight is 400~7,000,000,
The polyoxyethylene for being more preferably 4,000,000,5,000,000 or 7,000,000 including molecular weight；The rush osmopolymer accounts for boosting layer total weight
45~90%, preferably 50~85%, more preferably 60~80%, most preferably 68.5%, 68.2% or 77.5%.
In the boosting layer, the penetrating agent preferably includes one or more of sodium chloride, sucrose and mannitol；Institute
State penetrating agent accounts for boosting layer gross mass 5~45%, preferably 10~40%, more preferably 15~35%, most preferably 20~
30%, specifically, in an embodiment of the present invention, can be used 28.7%, 29.4 or 20.0%.
In the boosting layer, the colorant preferably includes iron oxide red, iron oxide yellow, iron oxide purple or iron oxide
It is black；The colorant accounts for the 0.1~4% of boosting layer gross mass, preferably 0.2~3%, more preferably 0.3~2%, specifically,
In an embodiment of the present invention, it can be used 0.3%.
In the boosting layer, the lubricant preferably include stearic acid, magnesium stearate, talcum powder, superfine silica gel powder one
Kind is several；The lubricant accounts for the 0.1~10% of boosting layer gross mass, preferably 0.5~8%, more preferably 1~5%, most
Preferably 2.1%, 2.2% or 2.4%.
Two-chamber osmotic pump drug release behavior is complicated, and the factor for influencing drug release behavior is more.Applicants have found that two-chamber osmotic
It pumps preparation drug release behavior early period mainly to be controlled by the permeability of medicated layer and drug solubility, the drug release of middle and later periods is mainly by boosting
The motive force and boosting layer of layer proportion in label regulate and control, wherein bulk pharmaceutical chemicals use the nitre after micronizing in medicated layer
Benzene Horizon, grain size can significantly improve the rate of releasing drug of early period between 10-30 μm, by setting between medicated layer and boosting layer
Ratio and penetrating agent and promote the dosage of osmopolymer and regulate and control the drug release behavior of middle and later periods, the results showed that, can significantly improve
Drug release rate.
In the present invention, coating is enclosed on the label, described includes filmogen and pore-foaming agent, the film forming
Material preferably includes one or more of cellulose acetate, ethyl cellulose and polymethacrylates；The pore-foaming agent is excellent
Choosing includes one or more of polyethylene glycol 200, polyethylene glycol 400 and Macrogol 600；The filmogen and pore-foaming agent
Mass ratio be 100：(5~30), preferably 100：(6~25), more preferably 100：(7~20), most preferably 100：(10~
15), specifically, can be 100 in an embodiment of the present invention:10 or 100:12.
In the present invention, the coating is semi-permeable membrane, and the coating is provided with release hole, the drug release in medicated layer side
The diameter in hole is preferably 0.5~2mm, more preferably 1~1.5mm；The coating weight gain is preferably 8~17%, that is, described
The quality of outer semi-transparent clothing film is the 8~17%, more preferably 9~15% of the label quality on Nifedipine controlled-release tablet, optimal
10~13% are selected as, specifically, can be 13.8%, 12.2% and 14.0% in an embodiment of the present invention.The present invention passes through
Penetrating agent is controlled simultaneously and promotees ratio, the weightening of coating and the ratio of medicated layer and boosting layer of osmopolymer, is realized
Control to Nifedipine controlled-release tablet drug release rate.
In the present invention, the Nifedipine controlled-release tablet preferably further includes light shield layer, and the light shield layer is wrapped in described half
Permeable membrane coating is outer, and the coating material of the light shield layer preferably includes the Opadry of Shanghai Colorcon Coating Technology Co., Ltd's offer
Product, specifically, in an embodiment of the present invention, Opadry 85G68918 products can be used.The weightening of the light shield layer is preferred
It is 1~5%, more preferably 2~4%.
The present invention also provides a kind of preparation methods of Nifedipine controlled-release tablet, include the following steps：
A) by 5~45% nifedipine, 25%~85% suspending agent, 1~25% penetrating agent and 0.5~10%
Mix lubricant obtains medicated layer material；
By 45~90% rush osmopolymer, 5~45% penetrating agent, 0.1~4% colorant and 0.1~10%
Mix lubricant, obtain boosting layer material；
B) by the step A) in medicated layer material and boosting layer material carry out tabletting, obtain double-deck core；
C) filmogen, pore-foaming agent and solvent are mixed, coating solution is obtained, using the coating solution to the step B)
To double-deck core be coated, obtain coating tablet, the mass ratio of the filmogen and pore-foaming agent is 100：(5~30)；
D) by the step C) in coating tablet medicated layer a side perforating, obtain Nifedipine controlled-release tablet.
In the present invention, type, dosage and the source of each ingredient of the medicated layer and each ingredient of boosting layer with it is above-mentioned
The type of each ingredient of medicated layer and each ingredient of boosting layer, dosage and source are consistent in technical solution, and details are not described herein.
Suspending agent, penetrating agent, lubricant, rush osmopolymer and colorant are preferably crossed 80 mesh and sieved by the present invention, nitre benzene
Then each ingredient of the medicated layer for being not added with lubricant will be mixed 10~15min respectively, is not added with the boosting layer of lubricant by flat micronizing
Each ingredient mixes 10~15min, is then respectively adding after lubricant and mixes 3~5min respectively again, obtains medicated layer material and helps
Push away a layer material.
After obtaining medicated layer material and boosting layer material, the present invention presses the medicated layer material and boosting layer material
Piece obtains double-layer chip, and in the present invention, the technique of the Double layer pellet is the common technical solution of those skilled in the art.
It is preferably 4~6kg/mm to suppress obtained double-layer chip hardness2, more preferably 4.5~5.5kg/mm2.Present invention preferably employs rule
Lattice are that the scrobicula mold of 9.0mm carries out the compacting of double-layer tablets.
The present invention mixes filmogen, pore-foaming agent and solvent, obtains coating solution, then uses the coating solution to described
Double-deck core is coated, and obtains coating tablet.In the present invention, the type and dosage of the filmogen and pore-foaming agent with it is above-mentioned
Filmogen and the type of pore-foaming agent are consistent with dosage in technical solution, and details are not described herein.In the present invention, institute's coating solution is molten
Agent (i.e. semi-permeable membrane coating solution solvent) is preferably acetone and water；The quality solid content of the coating solution is preferably 2~15%, more excellent
It is selected as 3~12%, most preferably 5~10%.
In the present invention, the piece bed tempertaure of the coating (semi-transparent film coating) is preferably 20~35 DEG C, more preferably 25~
30℃.The weightening of the coating is preferably 8~17%, more preferably 9~15%, most preferably 10~13%.
One side perforating of the coating tablet medicated layer is obtained Nifedipine controlled-release tablet by the present invention, present invention preferably employs
The method of laser boring or mechanical punching obtains release hole, in the present invention, the aperture of the release hole is preferably 0.5~
2mm, more preferably 1~1.5mm.The present invention does not have the position of the release hole special limitation, preferably at the center of tablet.
After completing punching, the present invention preferably wraps up one layer of light shield layer again on the coating tablet of the punching, plays the work of shading
With the present invention preferably mixes light screening material with water, obtains light shield layer solution, is then wrapped to the coating tablet of the punching
Clothing obtains Nifedipine controlled-release tablet.In the present invention, the type of the light screening material and the light screening material in above-mentioned technical proposal
Dosage is consistent with source, and details are not described herein.In the present invention, the quality solid content of the light shield layer solution be preferably 5~
30%, more preferably 10~25%, most preferably 15~20%.
In the present invention, the piece bed tempertaure of the light shield layer coating is preferably 35~45 DEG C, more preferably 40~43 DEG C；Institute
The weightening for stating light shield layer is preferably 1~5%, that is, and the coating weight gain of the light shield layer is the 3~8% of the double-deck core quality,
More preferably 3~5%.
The present invention provides a kind of Nifedipine controlled-release tablet, including label and the coating that is wrapped on the label；It is described
Label includes medicated layer and the boosting layer that is compounded in medicated layer, and the coating is provided with release hole in the side of medicated layer；Institute
It includes following components to state medicated layer, in terms of the mass percent for accounting for medicated layer total weight：Nifedipine：5~45%；Suspending agent：
25%~85%；Penetrating agent：1~25%；Lubricant：0.5~10%；The boosting layer includes following components, to account for boosting layer
The mass percent meter of total weight：Promote osmopolymer：45~90%；Penetrating agent：5~45%；Colorant：0.1~4%；Profit
Lubrication prescription：0.1~10%；Described includes filmogen and pore-foaming agent, and the mass ratio of the filmogen and pore-foaming agent is
100：(5~30).Nifedipine controlled-release tablet provided by the invention is not necessarily to by limiting penetrating agent and promoting the ratio of osmopolymer
The other slow-release materials of addition, can reach preferable slow release effect, and raw material composition is simple and easy to get, is convenient for industrialization production.It is real
Test the result shows that, the present invention in Nifedipine controlled-release tablet in 0~20 hour zero-order release, accumulative releasing degree reaches within 24 hours
90% or more.
In addition, the active ingredient delivery rate of the Nifedipine controlled-release tablet of the present invention is stable, appearance is good, preparation process
Simply, the advantages that convenient to take, quality controllable suitable amplification production.
In order to further illustrate the present invention, described to a kind of Nifedipine controlled-release provided by the invention with reference to embodiments
Piece and preparation method thereof is described in detail, but cannot be understood as limiting the scope of the present invention.
Embodiment 1：
Medicated layer prescription (every amount)：
Boosting layer prescription (every amount)：
Controlled release clothing prescription (1000 amounts)：
Light shield layer prescription (1000 amounts)：
Opadry 85G68918 9g；
Water 200g.
According to above-mentioned formula, respectively in the case where being not added with lubricant by each component of each component of medicated layer and boosting layer
10min is mixed, 3min is mixed respectively again after lubricant is added, uniformly mixed medicated layer and boosting layer material is taken, using 9.0mm
Scrobicula grinding tool carries out the compacting of double-layer tablets, tablet hardness 4kg/mm2；
Pressed double-deck core packet semipermeable membrane, the solid content of controlled release clothing coating solution are 5%, piece bed tempertaure at 20 DEG C,
Coating weight gain is 13.8%.
By the tablet after the completion of coating in the laser boring of medicated layer side, aperture 0.5mm.
Finally packet thin film clothing obtains Nifedipine controlled-release tablet, and it is 5% that light shield layer, which is coated fluid solid content, piece bed tempertaure
It it is 35 DEG C, the coating weight gain of light shield layer is 5%.
The present invention tests the 0.5% dodecyl sulphur for being 6.8 in pH for the Nifedipine controlled-release tablet that the present embodiment obtains
Drug release behavior in acid sodium solution, the results are shown in Figure 1, and Fig. 1 is that the drug release of the Nifedipine controlled-release tablet in the embodiment of the present invention 1 is bent
Line.
Embodiment 2：
Medicated layer prescription (every amount)：
Boosting layer prescription (every amount)：
Controlled release clothing prescription (1000 amounts)：
Opadry190004 30g；
Acetone 1000g；
Water 90g；
Light shield layer prescription (1000 amounts)：
Opadry 85G68918 8.5g；
Water 190g.
According to above-mentioned formula, respectively in the case where being not added with lubricant by each component of each component of medicated layer and boosting layer
15min is mixed, 5min is mixed respectively again after lubricant is added, uniformly mixed medicated layer and boosting layer material is taken, using 9.0mm
Scrobicula grinding tool carries out the compacting of double-layer tablets, tablet hardness 6kg/mm2；
Pressed double-deck core packet semipermeable membrane, the solid content of controlled release clothing coating solution are 5%, piece bed tempertaure at 35 DEG C,
Coating weight gain is 12.2%.
By the tablet after the completion of coating in the laser boring of medicated layer side, aperture 1.5mm.
Finally packet thin film clothing obtains Nifedipine controlled-release tablet, and it is 25% that light shield layer, which is coated fluid solid content, piece bed tempertaure
It it is 40 DEG C, the coating weight gain of light shield layer is 4.5%.
The present invention tests the 0.5% dodecyl sulphur for being 6.8 in pH for the Nifedipine controlled-release tablet that the present embodiment obtains
Drug release behavior in acid sodium solution, the results are shown in Figure 2, and Fig. 2 is that the drug release of the Nifedipine controlled-release tablet in the embodiment of the present invention 2 is bent
Line.
Embodiment 3：
Medicated layer prescription (every amount)：
Boosting layer prescription (every amount)：
Controlled release clothing prescription (1000 amounts)：
Light shield layer prescription (1000 amounts)：
Opadry 85G68918 9g；
Water 200g.
According to above-mentioned formula, respectively in the case where being not added with lubricant by each component of each component of medicated layer and boosting layer
15min is mixed, 5min is mixed respectively again after lubricant is added, uniformly mixed medicated layer and boosting layer material is taken, using 9.0mm
Scrobicula grinding tool carries out the compacting of double-layer tablets, tablet hardness 5kg/mm2；
Pressed double-deck core packet semipermeable membrane, the solid content of controlled release clothing coating solution are 10%, piece bed tempertaure at 35 DEG C,
Coating weight gain is 14%.
By the tablet after the completion of coating in the laser boring of medicated layer side, aperture 2mm.
Finally packet thin film clothing obtains Nifedipine controlled-release tablet, and it is 15% that light shield layer, which is coated fluid solid content, piece bed tempertaure
It it is 45 DEG C, the coating weight gain of light shield layer is 5%.
The present invention tests the 0.5% dodecyl sulphur for being 6.8 in pH for the Nifedipine controlled-release tablet that the present embodiment obtains
Drug release behavior in acid sodium solution, the results are shown in Figure 3, and Fig. 3 is that the drug release of the Nifedipine controlled-release tablet in the embodiment of the present invention 3 is bent
Line.
Comparative example 1
Medicated layer prescription (every amount)：
Boosting layer prescription (every amount)：
Semi-permeable membrane prescription and light shield layer prescription are the same as embodiment 3
According to above-mentioned formula, respectively in the case where being not added with lubricant by each component of each component of medicated layer and boosting layer
15min is mixed, 5min is mixed respectively again after lubricant is added, uniformly mixed medicated layer and boosting layer material is taken, using 9.0mm
Scrobicula grinding tool carries out the compacting of double-layer tablets, tablet hardness 5kg/mm2；
Pressed double-deck core packet semipermeable membrane, the solid content of controlled release clothing coating solution are 8%, piece bed tempertaure at 30 DEG C,
Coating weight gain is 13%.
By the tablet after the completion of coating in the laser boring of medicated layer side, aperture 2mm.
Finally packet thin film clothing obtains Nifedipine controlled-release tablet, and it is 15% that light shield layer, which is coated fluid solid content, piece bed tempertaure
It it is 40 DEG C, the coating weight gain of light shield layer is 5.0%.
The present invention tests the 0.5% dodecyl sulphur for being 6.8 in pH for the Nifedipine controlled-release tablet that this comparative example obtains
Drug release behavior in acid sodium solution, the results are shown in Figure 4, and Fig. 4 is the Nifedipine controlled-release in the embodiment of the present invention 3 and comparative example 1
The drug release profiles of piece.PVP K-90 D, hydroxypropyl methylcellulose K15M and copolyvidone S630 these volumes are added in this comparative example
Outer slow-release material, as seen from Figure 4, the Nifedipine sustained release tablets in the embodiment of the present invention 3 are additionally added with comparative example 1
There is no significant difference for the drug release profiles of the Nifedipine sustained release tablets of slow-release material, illustrates the nitre in the embodiment of the present invention 3
Although benzene Horizon sustained release tablets do not use additional slow-release material, its controlled-release effect and the tablet of slow-release material is used to imitate
Fruit is suitable.
Comparative example 2
Nifedipine grain size selects 120 ± 30 μm in medicated layer, remaining composition is the same as embodiment 1.
According to above-mentioned formula, respectively in the case where being not added with lubricant by each component of each component of medicated layer and boosting layer
15min is mixed, 5min is mixed respectively again after lubricant is added, uniformly mixed medicated layer and boosting layer material is taken, using 9.0mm
Scrobicula grinding tool carries out the compacting of double-layer tablets, tablet hardness 5kg/mm2；
Pressed double-deck core packet semipermeable membrane, the solid content of controlled release clothing coating solution are 8%, piece bed tempertaure at 32 DEG C,
Coating weight gain is 13.5%.
By the tablet after the completion of coating in the laser boring of medicated layer side, aperture 0.5mm.
One layer of shading film clothing is finally wrapped, obtains Nifedipine controlled-release tablet, it is 20% that light shield layer, which is coated fluid solid content, piece bed
Temperature is 35 DEG C, and the coating weight gain of light shield layer is 5%.
The present invention tests the 0.5% dodecyl sulphur for being 6.8 in pH for the Nifedipine controlled-release tablet that the present embodiment obtains
Drug release behavior in acid sodium solution, the results are shown in Figure 5, and Fig. 5 is that the drug release of the Nifedipine controlled-release tablet in the embodiment of the present invention 2 is bent
Line, 2 drug release profiles drug release early period of comparative example are significantly lower than 2 drug release profiles of embodiment.
Comparative example 3
Boosting layer prescription (every amount)：
Controlled release clothing prescription (1000 amounts)：
Opadry190004 34g；
Acetone 326g；
Water 17g；
Light shield layer prescription (1000 amounts)：
Opadry 85G68918 11g；
Water 73g.
According to above-mentioned formula, respectively in the case where being not added with lubricant by each component of each component of medicated layer and boosting layer
15min is mixed, 5min is mixed respectively again after lubricant is added, uniformly mixed medicated layer and boosting layer material is taken, using 9.0mm
Scrobicula grinding tool carries out the compacting of double-layer tablets, tablet hardness 5kg/mm2；
Pressed double-deck core packet semipermeable membrane, the solid content of controlled release clothing coating solution are 9%, piece bed tempertaure at 32 DEG C,
Coating weight gain is 12%.
By the tablet after the completion of coating in the laser boring of medicated layer side, aperture 2mm.
Finally packet thin film clothing obtains Nifedipine controlled-release tablet, and it is 15% that light shield layer, which is coated fluid solid content, piece bed tempertaure
It it is 40 DEG C, the coating weight gain of light shield layer is 4%.
The present invention tests the 0.5% dodecyl sulphur for being 6.8 in pH for the Nifedipine controlled-release tablet that the present embodiment obtains
Drug release behavior in acid sodium solution, the results are shown in Figure 6, and Fig. 6 is the Nifedipine controlled-release tablet of the embodiment of the present invention 2 and comparative example 3
Drug release profiles, the mass ratio of medicated layer and boosting layer is 1 in comparative example 3:1, drug release profiles are from rate of releasing drug after 12 hours
It increases sharply, hence it is evident that be higher than the drug release profiles of embodiment 2, illustrate that its controlled release properties is bad, and after 24 hours tired of comparative example 3
It counts release medicine and is less than embodiment 2.
Comparative example 4
Core formulation and light shield layer prescription with embodiment 1,
Semi-permeable membrane prescription (1000 amounts)：
According to above-mentioned formula, respectively in the case where being not added with lubricant by each component of each component of medicated layer and boosting layer
15min is mixed, 5min is mixed respectively again after lubricant is added, uniformly mixed medicated layer and boosting layer material is taken, using 9.0mm
Scrobicula grinding tool carries out the compacting of double-layer tablets, tablet hardness 5kg/mm2；
Pressed double-deck core packet semipermeable membrane, the solid content of controlled release clothing coating solution are 10%, piece bed tempertaure at 30 DEG C,
Coating weight gain is 8%.
By the tablet after the completion of coating in the laser boring of medicated layer side, aperture 2mm.
One layer of shading film clothing is finally wrapped, obtains Nifedipine controlled-release tablet, it is 20% that light shield layer, which is coated fluid solid content, piece bed
Temperature is 35 DEG C, and the coating weight gain of light shield layer is 5%.
The present invention tests the 0.5% dodecyl sulphur for being 6.8 in pH for the Nifedipine controlled-release tablet that the present embodiment obtains
Drug release behavior in acid sodium solution, the results are shown in Figure 7, and Fig. 7 is the Nifedipine controlled-release tablet of the embodiment of the present invention 1 and comparative example 4
Drug release profiles, coating weight gain is 8% in comparative example 4, and whole drug release profiles of comparative example 4 are apparently higher than the drug release of embodiment 1
Curve has discharged completely for basic 16 hours, and rate of release is too fast, it cannot be guaranteed that one day only with a piece of survival dose, and comparative example 4
Accumulative releasing degree medicine after 24 hours is less than embodiment 1.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (8)
1. a kind of Nifedipine controlled-release tablet, including label and the coating that is wrapped on the label；
The label includes medicated layer and the boosting layer that is compounded in medicated layer, and the coating is provided in the side of medicated layer to be released
Medicine hole；
The medicated layer is composed of the following components, in terms of the mass percent for accounting for medicated layer total weight：
Nifedipine micro mist：5~45%；
Suspending agent：35%~80%；
Penetrating agent：4~10%；
Lubricant：0.5~10%；
The suspending agent is the polyoxyethylene that molecular weight is 10~900,000；The grain size of the nifedipine micro mist is 10~30 μm；
The boosting layer is composed of the following components, in terms of the mass percent for accounting for boosting layer total weight：
Promote osmopolymer：60~77.5%；
Penetrating agent：20~30%；
Colorant：0.1~4%；
Lubricant：0.1~10%；
Described includes filmogen and pore-foaming agent, and the mass ratio of the filmogen and pore-foaming agent is 100：(5~30)；
The Nifedipine Tablets are prepared in accordance with the following methods：
A) by 5~45% nifedipine micro mist, 35%~80% suspending agent, 4~10% penetrating agent and 0.5~10%
Mix lubricant obtains medicated layer material；
The suspending agent is the polyoxyethylene that molecular weight is 10~900,000；
By 60~77.5% rush osmopolymer, 20~30% penetrating agent, 0.1~4% colorant and 0.1~10%
Mix lubricant obtains boosting layer material；
B) by the step A) in medicated layer material and boosting layer material carry out tabletting, obtain double-deck core；
C) using coating solution to the step B) obtained double-deck core is coated, coating tablet is obtained,
The coating solution includes filmogen, pore-foaming agent and solvent；
D) by the step C) in coating tablet medicated layer a side perforating, obtain Nifedipine controlled-release tablet.
2. Nifedipine controlled-release tablet according to claim 1, which is characterized in that in the medicated layer, the penetrating agent
Including one or more of sodium chloride, sucrose and mannitol；
The lubricant includes the one or more of stearic acid, magnesium stearate, talcum powder, superfine silica gel powder.
3. Nifedipine controlled-release tablet according to claim 1, which is characterized in that the lubricant accounts for the medicated layer gross weight
The 1~8% of amount.
4. Nifedipine controlled-release tablet according to claim 1, which is characterized in that in the boosting layer, the rush infiltration
Polymer includes the polyoxyethylene that molecular weight is 400~7,000,000；
The penetrating agent includes one or more of sodium chloride, sucrose and mannitol；
The colorant includes iron oxide red, iron oxide yellow, iron oxide purple or iron oxide black；
The lubricant includes the one or more of stearic acid, magnesium stearate, talcum powder, superfine silica gel powder.
5. Nifedipine controlled-release tablet according to claim 1, which is characterized in that in the boosting layer, the rush infiltration
Polymer accounts for the 60~77.5% of the boosting layer total weight；
The colorant accounts for the 0.2~3% of the boosting layer total weight；
The lubricant accounts for the 0.5~8% of the boosting layer total weight.
6. Nifedipine controlled-release tablet according to claim 1, which is characterized in that the matter of the medicated layer and the boosting layer
Amount is than being 1：(0.4~2.0).
7. Nifedipine controlled-release tablet according to claim 1, which is characterized in that the coating weight gain is 8~17%.
8. according to the Nifedipine controlled-release tablet described in claim 1~7 any one, which is characterized in that the nifedipine control
It further includes the light shield layer being wrapped in the coating to release piece.
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| CN109172534B (en) * | 2018-10-23 | 2020-08-07 | 迪沙药业集团有限公司 | Nifedipine sustained-release tablet composition |
| CN109568283B (en) * | 2018-12-28 | 2020-08-28 | 地奥集团成都药业股份有限公司 | Nifedipine sustained release tablet and preparation method thereof |
| CN114053237A (en) * | 2020-07-30 | 2022-02-18 | 上海汉都医药科技有限公司 | Controlled release tablet and preparation method thereof |
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| CN102138912A (en) * | 2010-12-03 | 2011-08-03 | 中国药科大学 | Nifedipine osmotic pump controlled release tablet and preparation method thereof |
| CN103565769A (en) * | 2012-07-18 | 2014-02-12 | 石药集团中奇制药技术（石家庄）有限公司 | Nifedipine controlled release composition and preparation method thereof |
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| US20120301546A1 (en) * | 2011-05-26 | 2012-11-29 | Hassan Emadeldin M | Acid-resistant soft gel compositions |
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| CN102138912A (en) * | 2010-12-03 | 2011-08-03 | 中国药科大学 | Nifedipine osmotic pump controlled release tablet and preparation method thereof |
| CN103565769A (en) * | 2012-07-18 | 2014-02-12 | 石药集团中奇制药技术（石家庄）有限公司 | Nifedipine controlled release composition and preparation method thereof |
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