CN107115308A - A kind of hydrocortisone two-phase sustained-release tablet composition - Google Patents
A kind of hydrocortisone two-phase sustained-release tablet composition Download PDFInfo
- Publication number
- CN107115308A CN107115308A CN201610099697.1A CN201610099697A CN107115308A CN 107115308 A CN107115308 A CN 107115308A CN 201610099697 A CN201610099697 A CN 201610099697A CN 107115308 A CN107115308 A CN 107115308A
- Authority
- CN
- China
- Prior art keywords
- hydrocortisone
- release tablet
- tablet core
- polyoxyethylene
- extension
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- 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
- A61K9/28—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of hydrocortisone two-phase sustained-release tablet composition, it is characterized in that hydrocortisone is contained in the coating of release immediately in extension release tablet core and in the tablet core, the extension release tablet core, by extension release tablet core percentage by weight calculate, comprising polyvinylpyrrolidone 0.5~1%；Carbomer 10~30.2%；Polyoxyethylene 200k 8~20.2%；Polyoxyethylene 7000k 10.1~30.1%；Microcrystalline cellulose 20.1~35.2%；Pregelatinized starch accounts for 5.3~16.6%；Colloidal silica accounts for 1~2%；Magnesium stearate accounts for 1~2%；The amount for being present in the hydrocortisone in the extension release tablet core is 80% to the 74% of hydrocortisone gross weight.
Description
Technical field
The present invention relates to a kind of glucocorticoid two-phase slow releasing composition, more particularly to a kind of hydrocortisone two-phase
Sustained-release tablet composition.
Background technology
Cortisol is the main glucocorticoid of the mankind, accounts for the 95% of whole glucocorticoids, produces under normal circumstances
Raw speed is 10mg/d, is roughly equal to 20~30mg/d of hydrocortisone, level of serum cortisol reaches in 8am
The μ g/L of peak about 160, the μ g/L of low ebb about 40 are reached in 4pm.Cortisol effect include adjust carbohydrate/
Albumen and fat metabolism, anti-inflammatory and immunosuppressive action, maintain cardiovascular integrality and blood sugar level etc..By
In the most adrenal tissues of the destruction bilateral such as autoimmunity, tuberculosis, infection, tumour, there are a variety of cortex
Hypohormonal performance, claims adrenocortical insufficiency (Adrenal cortical Insufficiency).Kidney
Upper gland cortical hypofunction can use glucocorticoid replacement therapy, generally use hydrocortisone or cortisone
Orally, simulation human hormone secretion circadian rhythm.
Standard treatment in glucocorticoid replacement therapy includes applying three times a day, and such as dosage is 5-20mg
Hydrocortisone, daily accumulated dose be 15-60mg hydrocortisone.The correct dose applied is usual
Originated and according to the subjective response of patient from low dosage glucocorticoid based on each doctor's experience
Judge.Gradually increase if subject shows and lacks response (in the example that glucocorticoid lacks)
Dosage reduces dosage if curer shows the excessive symptom of glucocorticoid.
2011 ViroPharm companies (former DuoCort companies) had listed in Europe hydrocortisone two-phase delay
Release piece, trade nameThe hydrocortisone two-phase sustained release tablets outer layer is quick release, is taken medicine from morning
After can reach one peak of physiological regulation faster, internal layer discharges for sustained release, can more conform to Human Physiology shape
Glucocorticoid change in concentration under state, while the demand of patient's medication in one day once can be met.
Original grind patent application CN200580011862, CN201210499801, CN201080016169.6 and
The prescription and preparation technology of hydrocortisone two-phase controlled-release preparation composite are disclosed in CN201180025139.
Hydrocortisone two-phase releasing piece is listed with reference to European UnionSpecification ingredients listed and original grind patent
Prescription listed by CN201080016169 and CN201180025139 carries out supplementary material compatibility test.Will be all
(hydroxypropyl methylcellulose K 100cP, hydroxypropyl methylcellulose K 4000cP, microcrystalline cellulose, pregelatinated form sediment auxiliary material
Powder, colloidal silica, magnesium stearate,II) mixed respectively with hydrocortisone with certain proportion,
Placed 30 days in 60 DEG C of high temperature, 92.5%RH, in illumination illumination 5000Luxhr, total illumination 1.2 × 106Lux
Under conditions of place 10 days, check relevant material.As a result hydroxypropyl methylcellulose K 100cP and hydroxypropyl first are found
The mixture of cellulose K 4000cP and hydrocortisone is under these conditions in placement process, and relevant material increases
It is long very fast.Referring concurrently to the former embodiment ground in patent CN201080016169 and CN201180025139
Prescription and technique prepare hydrocortisone two-phase sustained release tablets (referring to comparative examples 1) and have purchased commercially available original
Product are ground, factors influencing experiment is carried out, as a result find that the relevant material of two groups of samples increases more, together
When 5 days, 10 days, the stripping curve of 30 days and f when 02Value changes are also larger.
Original grinds to introduce in patent CN201080016169 realizes hydrocortisone two-phase using direct powder compression
Release, thus it is higher to auxiliary material and technological requirement, for example：Selection suitably disclosure satisfy that direct tablet compressing requirement
Auxiliary material, tablet weight variation are larger, the difficult satisfaction of uniformity of dosage units is required, dissolution rate problem especially grinds medicine with original
External pharmacy consistent (referring mainly to a plurality of stripping curve consistent) is extremely difficult to.
On January 20th, 2012, State Council issues《On printing and distributing national drug safety " 12 " planning
Notice》(promulgated by the State Council (2012) 5, hereinafter referred to as《Notify》) it is mentioned that will be at following 10 years to
Domestic chemical imitation medicine is listed to carry out and the former Conformance Assessment for grinding medicine.At this stage, the quality evaluation of imitation medicine leads to
In terms of Chang Yousan, i.e., external pharmacy consistent (referring mainly to a plurality of stripping curve consistent), vivo biodistribution availability one
Cause (i.e. bioequivalence (BE) test successfully), clinical efficacy it is consistent (acquisition doctor, patient it is extensive
Accreditation).Triadic relation is complementary to one another, complemented each other.When the external a plurality of stripping curve of imitation medicine grinds medicine with original
Unanimously, then both consistent probability of vivo biodistribution availability will be up to 90%.Imitation medicine as developed is a plurality of in vitro
Stripping curve grinds medicine with original and differed greatly, then both inconsistent probability of vivo biodistribution availability also will be up to
The mortality of 90%, BE experiment is high.According to State Food and Drug Administration on December 31st, 2013
Issue《Normal oral solid pharmaceutical preparation stripping curve is determined with being compared guideline (draft)》(hereinafter referred to as
Draft) propose using similar factors (f2) method is when comparing stripping curve similitude, unless otherwise specified, two
Stripping curve similar factors (f2) numerical value be not less than 50, it is believed that with similitude.f2Value is bigger, illustrates two
Person closer to.According to the requirement of draft, hydrocortisone two-phase sustained release tablets imitation medicine is in four kinds of different mediums
The dissolution row of (900ml water, pH1.2 hydrochloric acid, pH4.5 hac buffers, pH6.8 phosphate rush solution)
For that should be ground with commercially available originalIt is consistent.
Relative to wet granule compression tablet, because the density variation of medicine and auxiliary material, material exist during direct tablet compressing
Electrostatic is also easy to produce when dry-mixed so that the material of direct tablet compressing is easily layered, and causes weight differential and uniformity of dosage units
The problem of aspect.The micromeritis of itself control (such as compressibility, mobility, dilute for the auxiliary material of direct tablet compressing
Release potentiality, content uniformity, lubrication sensitiveness etc.) require higher, it is necessary to by what is especially processed, such as spray
Mist drying, fluidized bed drying, Rotary drying or cocrystallization etc., so the cost of these auxiliary materials is high, domestic auxiliary material
Majority can not meet vertical compression requirement.Patent CN201080016169 and CN201180025139 are being ground with reference to original
In embodiment prescription and technique prepare hydrocortisone two-phase sustained release tablets (referring to comparative examples 1)
During, the weight differential occurred between tablet is larger, and uniformity of dosage units is difficult the problems such as satisfaction is required.
In addition, requirement of the dry method direct tablet compressing to tablet press machine is also higher.Because dry method direct tablet compressing pressure is larger,
Abrasion to tablet press machine and punch die is more serious, can greatly shorten the utilization rate of equipment.Simultaneously in tableting processes,
Meeting powder is flown upward, and both pollutes environment, and harm worker is healthy again, can also cause the waste of raw and auxiliary material.
The production of country's tablet kind at present is still based on wet granule compression tablet method, the production line profit of compressing dry granulation
It is low with rate.
It is an object of the invention to provide it is a kind of it is easy to operate, be easy to industrialized production and difference is small, easy to control the quality
A kind of hydrocortisone two-phase sustained-release tablet, the tablet and commercially available productWith similar dissolution row
For while more former grind more stable property.
The content of the invention
We attempt to change to hydrocortisone release when carrying out the screening of hydrocortisone two-phase sustained-release tablet recipe
The larger framework material (hydroxypropyl methylcellulose K 100cP, hydroxypropyl methylcellulose K 4000cP) of influence, it is unexpected
It was found that from a certain proportion of polyoxyethylene 200k, polyoxyethylene 7000k and carbomer as framework material,
With commercially available productWith similar dissolved corrosion, at the same influence factor experiment in, main ingredient it is relevant
Material is compared with the hydrocortisone two-phase sustained release prepared with reference to the former embodiment 1 ground in patent CN201180025139
Piece (referring to comparative examples 1), the commercially available original of purchase are ground compared to smaller, the f of four stripping curves of growth2Value
It is almost unchanged compared with when 0.
The present invention relates to a kind of hydrocortisone two-phase sustained-release tablet composition, it is characterised in that includes：
(a) 1-80mg hydrocortisone, it is contained in extension release tablet core and the tablet core
On release immediately be coated in；
(b) the extension release tablet core, is calculated by the percentage by weight of extension release tablet core, comprising
Polyvinylpyrrolidone 0.5~1%；Carbomer 10~30.2%；Polyoxyethylene 200k 8~20.2%；Polyoxy second
Alkene 7000k 10.1~30.1%；Microcrystalline cellulose 20.1~35.2%；Pregelatinized starch accounts for 5.3~16.6%；Colloidal state
Silica accounts for 1~2%；Magnesium stearate accounts for 1~2%；It is present in the hydrogenation in the extension release tablet core
The amount of cortisone is 80% to the 74% of hydrocortisone gross weight；
(c) hydrocortisone and quick-release coating membrane are included in the coating of release immediately, the quick-release coating membrane contains
There are coating material, plasticizer and antiplastering aid, the amount for being present in the hydrocortisone in the coating of release immediately is
20% to the 26% of hydrocortisone gross weight.
A kind of described hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the extension release tablet
Core, is calculated by the percentage by weight of extension release tablet core, includes 1% polyvinylpyrrolidone；30.2%
Carbomer；8.1% polyoxyethylene 200k；10.1% polyoxyethylene 7000k；35.2% microcrystalline cellulose
Element；5.8% pregelatinized starch；1% colloidal silica；1% magnesium stearate；7.6% hydrogenation can
Pine.
A kind of described hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the extension release tablet
Core, is calculated by the percentage by weight of extension release tablet core, includes 1% polyvinylpyrrolidone；10%
Carbomer；8% polyoxyethylene 200k；30.1% polyoxyethylene 7000k；35.1% microcrystalline cellulose；
5.3% pregelatinized starch；1% colloidal silica；1.5% magnesium stearate；8% hydrocortisone.
A kind of described hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the extension release tablet
Core, is calculated by the percentage by weight of extension release tablet core, includes 1% polyvinylpyrrolidone；15.1%
Carbomer；20.2% polyoxyethylene 200k；15.1% polyoxyethylene 7000k；20.1% microcrystalline cellulose
Element；16.6% pregelatinized starch；2% colloidal silica；2% magnesium stearate；7.8% hydrogenation can
Pine.
A kind of described hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the extension release tablet
Core, is calculated by the prescription percentage by weight of extension release tablet core, includes 0.5% polyvinylpyrrolidine
Ketone；20.2% carbomer；17.3% polyoxyethylene 200k；10.1% polyoxyethylene 7000k；30.3%
Microcrystalline cellulose；10.1% pregelatinized starch；2% colloidal silica；2% magnesium stearate；7.6%
Hydrocortisone.
A kind of described hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the extension release tablet
Core, is calculated by the prescription percentage by weight of extension release tablet core, includes 0.5% polyvinylpyrrolidine
Ketone；25.3% carbomer；8.1% polyoxyethylene 200k；25.3% polyoxyethylene 7000k；25.3%
Microcrystalline cellulose；6.1% pregelatinized starch；1% colloidal silica；1% magnesium stearate；7.5%
Hydrocortisone.
Described a kind of hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the coating material is selected from
Methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidine
One or more in ketone K12-90, polyvinyl alcohol；The plasticizer is selected from polyethylene glycol, glycerine, the third two
One or more in alcohol；The one kind or many of the antiplastering aid in talcum powder, magnesium stearate, silica
Kind.
Described a kind of hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the coating material is poly-
Vinyl alcohol, the plasticizer is polyethylene glycol, and the antiplastering aid is talcum powder.
A kind of described hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the quick-release coating membrane bag
Containing colouring agent, the one kind of the colouring agent in titanium dioxide, iron oxide red, iron oxide black, lycopene
Or it is a variety of.
Described a kind of hydrocortisone two-phase sustained-release tablet composition, it is characterised in that the colouring agent is dioxy
Change titanium.
Found during formulation study, as selection polyoxyethylene 200k, polyoxyethylene 7000k and Ka Bo
Nurse as framework material, only it is proportional within the above range, prepared hydrogenation can two-phase sustained release tablets dissolution
Behavior is just ground with original and is consistent.
Brief description of the drawings：
Fig. 1 be inventive embodiments 1 prepare hydrogenation can two-phase sustained release tablets and original grindIn the aqueous solution
In stripping curve
Fig. 2 be inventive embodiments 1 prepare hydrogenation can two-phase sustained release tablets and original grindIn pH1.2
Stripping curve in hydrochloric acid solution
Fig. 3 be inventive embodiments 1 prepare hydrogenation can two-phase sustained release tablets and original grindIn pH4.5
Stripping curve in hac buffer
Fig. 4 be inventive embodiments 1 prepare hydrogenation can two-phase sustained release tablets and original grindIn pH6.8
The stripping curve that phosphate is rushed in solution
Embodiment：
Below will by embodiment, the invention will be further described, these descriptions are not to present invention
It is further limited.It should be understood by those skilled in the art that being equal for being made to the technical characteristic of the present invention is replaced
Change, or be correspondingly improved, still fall within protection scope of the present invention.
Following inventive embodiments use the hydrocortisone raw material of same lot number.
Granulator：The multi-functional wet mixing pelletizer of Shenzhen Xinyi spy's science and technology G6 test-types
Fluid bed：German GmbH companies Glatt fluid bed models：GPCG-11
Digestion instrument：Haiyida Science and Technology Co., Ltd., Tianjin's model：RCY-808
The hydrocortisone two-phase sustained release tablets of inventive embodiments 1
The prescription of table 1
By composition above, 1000 (specifications of hydrocortisone two-phase sustained release tablets are prepared：Hydrogenation can
Loose 20mg).
Preparation method：
1) release tablet core is extended：According to extension release tablet core prescription, the medical active will be contained
Composition, adhesive, the mixture of diluent, which are made after wet grain, adds glidant and lubricant and tabletting.
2) release is coated immediately：Prescription is coated according to release immediately, by hydrocortisone, antitackiness agent and coating
The hydrocortisone that liquid (Opadry II and water) coating is discharged immediately with obtaining.
3) coating will be discharged immediately to be wrapped in outside extension release tablet core, obtain hydrocortisone two-phase sustained release
Piece.
The hydrocortisone two-phase sustained release tablets of inventive embodiments 2
The prescription of table 2
By composition above, 1000 (specifications of hydrocortisone two-phase sustained release tablets are prepared：Hydrogenation can
Loose 20mg).
Preparation technology：With reference to inventive embodiments 1.
The hydrocortisone two-phase sustained release tablets of inventive embodiments 3
The prescription of table 3
By composition above, 1000 (specifications of hydrocortisone two-phase sustained release tablets are prepared：Hydrogenation can
Loose 20mg).
Preparation technology：With reference to inventive embodiments 1.
The hydrocortisone two-phase sustained release tablets of inventive embodiments 4
The prescription of table 4
By composition above, 1000 (specifications of hydrocortisone two-phase sustained release tablets are prepared：Hydrogenation can
Loose 20mg).
Preparation technology：With reference to inventive embodiments 1.
The hydrocortisone two-phase sustained release tablets of inventive embodiments 5
The prescription of table 5
By composition above, 1000 (specifications of hydrocortisone two-phase sustained release tablets are prepared：Hydrogenation can
Loose 20mg).
Preparation technology：With reference to inventive embodiments 1.
The hydrocortisone two-phase sustained release tablets influence factor of inventive embodiments 6 is tested
Take the original of 1~5 group of sample of inventive embodiments, comparative examples 1~4 and purchase to grind commercial samples, refer to《Change
Learn medicine (bulk drug and preparation) stability study technological guidance's principle》In influence factor test requirements document, will
10 groups of samples respectively 60 DEG C of high temperature, high humidity 92.5%RH place 30 days, respectively 0 day, 5 days, 10
It was sampled with 30 days, in illumination illumination 5000Luxhr, total illumination 1.2 × 106Under conditions of Lux, 10 are placed
My god, sampled respectively 0 day, 5 days, 10 days, relevant material and dissolution rate are detected using HPLC methods.
Dissolution method：
Each 6 of each group sample under the conditions of different placements is taken respectively, in four kinds of different dissolution mediums (900ml water,
PH1.2 hydrochloric acid, pH4.5 hac buffers, pH6.8 phosphate rush solution), digestion instrument mixing speed 50rpm,
In different time points sampling, and by the dissolution rate of HPLC detection hydrocortisones, and calculate f2Value.
Table 6~8 lists relevant material in influence factor experiment and investigates result, as seen from the experiment, in influence
In the placement process of factor, comparative examples 1 and it is former grind commercially available sample it is total it is miscellaneous increase more, and invent and implement
The sample of example 1~5, it is total miscellaneous nearly no to rise appreciably.
Table 9~11 lists dissolution rate in influence factor experiment and investigates result.When 0, compared with original is ground, invention
The sample f of embodiment 1~5, comparative examples 12Value is all higher than 50, illustrates that its dissolved corrosion grinds commercially available with original
Unanimously, continue to investigate in the placement process of influence factor, its change about material and dissolution rate.To according to the facts
Apply a f for 2-4 samples2Value is less than 50, illustrates that its dissolved corrosion grinds commercially available inconsistent with original, does not continue to investigate.
Stripping curve when grinding commercially available product 0 using original compares in the placement process of influence factor as reference, and invention is real
Apply example 1~5, comparative examples 1 and the former f for grinding commercially available sample2The change of value, is invented as seen from the experiment
The dissolved corrosion of the sample of embodiment 1~5 is more stable under the conditions of the placement of influence factor.
6 high temperature of table, 60 DEG C of influence factors test relevant material and investigate result
The high humidity 92.5%RH influence factors of table 7 test relevant material and investigate result
The relevant material of the illumination effect factorial experiments of table 8 investigates result (illumination 5000Luxhr, total illumination 1.2 × 106Lux)
9 high temperature of table, 60 DEG C of influence factor experiment dissolution rate f2Value investigates result
The high humidity 92.5%RH influence factors of table 10 experiment dissolution rate f2Value investigates result
The illumination effect factorial experiments dissolution rate f of table 112Value investigates result
The hydrocortisone two-phase sustained release tablets of comparative examples 1
The prescription of table 12
Ground with reference to originalComposition, and original grind patent CN201080016169 and
The prescription and technique of embodiment in CN201180025139 prepare hydrocortisone two-phase sustained release tablets 1000
Piece (specification：Hydrocortisone 20mg).
Preparation technology：
1) release tablet core is extended：By extension release tablet core prescription by hydrocortisone and other auxiliary materials
Well mixed and vertical compression is label.
2) release is coated immediately：Prescription is coated according to release immediately, by hydrocortisone, antitackiness agent and coating
The hydrocortisone that liquid (Opadry II and water) coating is discharged immediately with obtaining.
3) coating will be discharged immediately to be wrapped in outside extension release tablet core, obtain hydrocortisone two-phase sustained release
Piece.
The hydrocortisone two-phase sustained release tablets of comparative examples 2
The prescription of table 13
By composition above, 1000 (specifications of hydrocortisone two-phase sustained release tablets are prepared：Hydrogenation can
Loose 20mg).
Preparation method：With reference to inventive embodiments 1
The hydrocortisone two-phase sustained release tablets of comparative examples 3
The prescription of table 14
By composition above, 1000 (specifications of hydrocortisone two-phase sustained release tablets are prepared：Hydrogenation can
Loose 20mg).
Preparation method：With reference to inventive embodiments 1
The hydrocortisone two-phase sustained release tablets of comparative examples 4
The prescription of table 15
By composition above, 1000 (specifications of hydrocortisone two-phase sustained release tablets are prepared：Hydrogenation can
Loose 20mg).
Preparation method：With reference to inventive embodiments 1.
Claims (10)
1. a kind of hydrocortisone two-phase sustained-release tablet composition, it is characterised in that include：
(a) 1-80mg hydrocortisone, it is contained in extension release tablet core and the tablet core
On release immediately be coated in；
(b) the extension release tablet core, is calculated by the percentage by weight of extension release tablet core, comprising
Polyvinylpyrrolidone 0.5~1%；Carbomer 10~30.2%；Polyoxyethylene 200k 8~20.2%；Polyoxy second
Alkene 7000k 10.1~30.1%；Microcrystalline cellulose 20.1~35.2%；Pregelatinized starch accounts for 5.3~16.6%；Colloidal state
Silica accounts for 1~2%；Magnesium stearate accounts for 1~2%；It is present in the hydrogenation in the extension release tablet core
The amount of cortisone is 80% to the 74% of hydrocortisone gross weight；
(c) hydrocortisone and quick-release coating membrane are included in the coating of release immediately, the quick-release coating membrane contains
There are coating material, plasticizer and antiplastering aid, the amount for being present in the hydrocortisone in the coating of release immediately is
20% to the 26% of hydrocortisone gross weight.
2. a kind of hydrocortisone two-phase sustained-release tablet composition as claimed in claim 1, it is characterised in that institute
Extension release tablet core is stated, is calculated by the percentage by weight of extension release tablet core, includes 1% poly- second
Alkene pyrrolidone；30.2% carbomer；8.1% polyoxyethylene 200k；10.1% polyoxyethylene 7000k；
35.2% microcrystalline cellulose；5.8% pregelatinized starch；1% colloidal silica；1% magnesium stearate；
7.6% hydrocortisone.
3. a kind of hydrocortisone two-phase sustained-release tablet composition as claimed in claim 1, it is characterised in that institute
Extension release tablet core is stated, is calculated by the percentage by weight of extension release tablet core, includes 1% poly- second
Alkene pyrrolidone；10% carbomer；8% polyoxyethylene 200k；30.1% polyoxyethylene 7000k；35.1%
Microcrystalline cellulose；5.3% pregelatinized starch；1% colloidal silica；1.5% magnesium stearate；8%
Hydrocortisone.
4. a kind of hydrocortisone two-phase sustained-release tablet composition as claimed in claim 1, it is characterised in that institute
Extension release tablet core is stated, is calculated by the percentage by weight of extension release tablet core, includes 1% poly- second
Alkene pyrrolidone；15.1% carbomer；20.2% polyoxyethylene 200k；15.1% polyoxyethylene 7000k；
20.1% microcrystalline cellulose；16.6% pregelatinized starch；2% colloidal silica；2% magnesium stearate；
7.8% hydrocortisone.
5. a kind of hydrocortisone two-phase sustained-release tablet composition as claimed in claim 1, it is characterised in that institute
Extension release tablet core is stated, is calculated by the prescription percentage by weight of extension release tablet core, including 0.5%
Polyvinylpyrrolidone；20.2% carbomer；17.3% polyoxyethylene 200k；10.1% polyoxyethylene
7000k；30.3% microcrystalline cellulose；10.1% pregelatinized starch；2% colloidal silica；2%
Magnesium stearate；7.6% hydrocortisone.
6. a kind of hydrocortisone two-phase sustained-release tablet composition as claimed in claim 1, it is characterised in that institute
Extension release tablet core is stated, is calculated by the prescription percentage by weight of extension release tablet core, including 0.5%
Polyvinylpyrrolidone；25.3% carbomer；8.1% polyoxyethylene 200k；25.3% polyoxyethylene
7000k；25.3% microcrystalline cellulose；6.1% pregelatinized starch；1% colloidal silica；1% it is hard
Fatty acid magnesium；7.5% hydrocortisone.
7. a kind of hydrocortisone two-phase sustained-release tablet composition as described in claim 1~6 is any, its feature
It is that the coating material is selected from methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl
One or more in cellulose, polyvinylpyrrolidone K12-90, polyvinyl alcohol；The plasticizer is selected from
One or more in polyethylene glycol, glycerine, propane diols；The antiplastering aid be selected from talcum powder, magnesium stearate,
One or more in silica.
8. a kind of hydrocortisone two-phase sustained-release tablet composition as claimed in claim 7, it is characterised in that institute
Coating material is stated for polyvinyl alcohol, the plasticizer is polyethylene glycol, the antiplastering aid is talcum powder.
9. a kind of hydrocortisone two-phase sustained-release tablet composition as described in claim 1~6 is any, its feature
It is that coating membrane is released described in speed includes colouring agent, the colouring agent is selected from titanium dioxide, iron oxide red, iron oxide
One or more in black, lycopene.
10. a kind of hydrocortisone two-phase sustained-release tablet composition as claimed in claim 9, it is characterised in that
The colouring agent is titanium dioxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610099697.1A CN107115308B (en) | 2016-02-23 | 2016-02-23 | Hydrocortisone biphasic sustained-release tablet composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610099697.1A CN107115308B (en) | 2016-02-23 | 2016-02-23 | Hydrocortisone biphasic sustained-release tablet composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107115308A true CN107115308A (en) | 2017-09-01 |
| CN107115308B CN107115308B (en) | 2021-02-23 |
Family
ID=59716903
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610099697.1A Active CN107115308B (en) | 2016-02-23 | 2016-02-23 | Hydrocortisone biphasic sustained-release tablet composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107115308B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1942176A (en) * | 2004-04-22 | 2007-04-04 | 杜奥科特公司 | Pharmaceutical compositions for glucocorticoid replacement therapy |
| CN101453993A (en) * | 2006-04-03 | 2009-06-10 | 伊萨·奥迪迪 | Controlled release delivery device comprising an organosol coat |
| WO2009118763A1 (en) * | 2008-03-28 | 2009-10-01 | Panacea Biotec Limited | Multilayered pharmaceutical compositions and processes thereof |
| CN102448464A (en) * | 2009-04-07 | 2012-05-09 | 杜奥科特药物公司 | Improved glucocorticoid therapy |
| NZ598486A (en) * | 2004-04-22 | 2013-01-25 | Duocort Pharma Ab | Pharmaceutical compositions methods and kit for glucocorticoid replacement therapy |
| CN102933218A (en) * | 2010-05-20 | 2013-02-13 | 杜奥科特药物公司 | Posology and administration of glucocorticoid based compositions |
-
2016
- 2016-02-23 CN CN201610099697.1A patent/CN107115308B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1942176A (en) * | 2004-04-22 | 2007-04-04 | 杜奥科特公司 | Pharmaceutical compositions for glucocorticoid replacement therapy |
| NZ598486A (en) * | 2004-04-22 | 2013-01-25 | Duocort Pharma Ab | Pharmaceutical compositions methods and kit for glucocorticoid replacement therapy |
| CN103006592A (en) * | 2004-04-22 | 2013-04-03 | 杜奥科特药物公司 | Pharmaceutical compositions for glucocorticoid replacement therapy |
| CN101453993A (en) * | 2006-04-03 | 2009-06-10 | 伊萨·奥迪迪 | Controlled release delivery device comprising an organosol coat |
| WO2009118763A1 (en) * | 2008-03-28 | 2009-10-01 | Panacea Biotec Limited | Multilayered pharmaceutical compositions and processes thereof |
| CN102448464A (en) * | 2009-04-07 | 2012-05-09 | 杜奥科特药物公司 | Improved glucocorticoid therapy |
| CN102933218A (en) * | 2010-05-20 | 2013-02-13 | 杜奥科特药物公司 | Posology and administration of glucocorticoid based compositions |
Non-Patent Citations (1)
| Title |
|---|
| 林宪政等: ""氢化可的松在肾上腺皮质功能不全危重患者治疗中的应用"", 《中华损伤与修复杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107115308B (en) | 2021-02-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20080038355A1 (en) | Bioadhesive dosage form of steroids | |
| CN102292071B (en) | Comprise the pharmaceutical composition of 2-OXo-1-pyrrolidine derivatives | |
| CN105213346B (en) | A kind of pharmaceutical composition and preparation method thereof containing cinacalcet hydrochloride | |
| CN109223724A (en) | Ferric citrate dosage forms | |
| DARZULI et al. | Selected excipients in oral solid dosage form with dry extract of Pyrola rotundifolia L. | |
| NO175884B (en) | Process for preparing a pressed tablet containing methylprednisolone and a super-disintegrant | |
| CN105193763A (en) | Vortioxetine hydrobromide tablets and preparation method thereof | |
| TWI252111B (en) | Matrix film tablet with controlled release of a natural mixture of conjugated estrogens | |
| CN104940152B (en) | A kind of pharmaceutical composition containing butanedioic acid Solifenacin | |
| CN109260160A (en) | A kind of valsartan amlodipine tablet and preparation method thereof | |
| CN106890129A (en) | The extended release dosage form of the general woods of ring benzyl | |
| CN105055350B (en) | A kind of preparation method of the tablet containing proton pump inhibitor | |
| CN103948553A (en) | Lamotrigine sustained release tablet and preparation method of lamotrigine sustained release tablet | |
| CN107115308A (en) | A kind of hydrocortisone two-phase sustained-release tablet composition | |
| CN102716132A (en) | Compound amlodipine/valsartan/hydrochlorothiazide tablets and method for making the same | |
| CN106456640A (en) | Ceritinib formulation | |
| CN109646417A (en) | A kind of Trimetazidine sustained release tablets and preparation method thereof | |
| CN107982230A (en) | A kind of uliprista acetate dispersible tablet and preparation method thereof | |
| CN108078933A (en) | A kind of tolvaptan dispersible tablet and preparation method thereof | |
| CN103446070B (en) | A kind of roflumilast solid immediate release preparation and preparation method thereof | |
| CN109498584A (en) | A kind of dispersible tablet and its novel processing step containing Letrozole | |
| CN105106963B (en) | Trimebutine maleate sustained-release preparation and preparation method thereof | |
| CN108785266A (en) | A kind of rosuvastatin calcium tablets agent and preparation method thereof | |
| CN104940157B (en) | A kind of Aceclofenac enteric coatel tablets and preparation method thereof | |
| CN104721163A (en) | Sustained release tablet containing lamotrigine and preparing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |