CN107137367A - Salbutamol sulfate oral disnitegration tablet and preparation method thereof - Google Patents
Salbutamol sulfate oral disnitegration tablet and preparation method thereof Download PDFInfo
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- CN107137367A CN107137367A CN201710214406.3A CN201710214406A CN107137367A CN 107137367 A CN107137367 A CN 107137367A CN 201710214406 A CN201710214406 A CN 201710214406A CN 107137367 A CN107137367 A CN 107137367A
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- salbutamol sulfate
- low
- tablet
- pvpp
- substituted hydroxypropyl
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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
- A61K9/2004—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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Abstract
The invention discloses a kind of salbutamol sulfate oral disnitegration tablet and preparation method thereof, the oral disnitegration tablet includes auxiliary material on the salbutamol sulfate and pharmacy of effective dose, auxiliary material is filler, flavouring, disintegrant, lubricant and adhesive in the pharmacy, it is characterised in that：The filler is mannitol and microcrystalline cellulose, the flavouring is mannitol, the disintegrant is PVPP and low-substituted hydroxypropyl cellulose, the lubricant is silica and magnesium stearate, described adhesive is purified water, wherein, the addition of adhesive purified water is mannitol, microcrystalline cellulose, 30% the 40% of the gross weight of 30~80% PVPP of total addition and low-substituted hydroxypropyl cellulose.Product disintegration time limited of the present invention is short, and tablet weight variation is small, and binder is water, and cost is low.The preparation method process equipment of product of the present invention is simple, easy to implement the method and controllable, and operating cost is low, economical, conveniently, can be mass-produced.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of salbutamol sulfate oral disnitegration tablet and its preparation side
Method.
Background technology
Salbutamol sulfate is the medicine that a class alleviates SOA, and selectively acting is in β2Acceptor, causes bronchus to expand
, patients in remission.Oral salbutamol sulfate ordinary tablet works after usual 30 minutes, is easily delayed best occasion for the treatment,
Be inconvenient to take common Salbutamol Sulfate in Tablet during other morbidity.To avoid the generation of above-mentioned phenomenon, a kind of new oral
Fast release solid formulation-oral disnitegration tablet, patient need not use water delivery service, and tablet is disintegrated rapidly in oral cavity, work rapid, carry significantly
High patient medication compliance.
At present, Chinese Pharmacopoeia has recorded salbutamol sulfate conventional tablet, parenteral solution, capsule, sustained release tablets, spansule
Deng, and the application of salbutamol sulfate oral disnitegration tablet and Patents are less, the success of salbutamol sulfate oral disnitegration tablet
Promote, preparation method therein is crucial.
The preparation method of existing salbutamol class oral disnitegration tablet has：
Patent No. CN200610151026.1 invention presses equal increments method by albuterol hydrochloride odor mask bag
Compound and disintegrant, filler, flavouring are well mixed, and disintegrated tablet are prepared using direct powder compression, because of salbutamol salt
Class poor fluidity, viscosity is strong, and tabletting easily occurs sticking, card and rushes phenomenon, therefore take direct powder compression to prepare salbutamol salt
There is tablet and disperse uneven in class oral disnitegration tablet, the problems such as tablet is easily overweight, not have producing feasibility.
Granted patent CN200310107658.4 prepares oral disnitegration tablet, specially Eudragit using wet granulation process
E-100 is coated rear wet granule compression tablet to main ingredient salbutamol, and its shortcoming is：1) preparation process complex process, multistep work
Sequence is related to drying, and highest drying temperature reaches 60 DEG C, has larger to salbutamol and the stability of its esters with thermal sensitivity
Influence；2) it is dried using stainless steel disc and baking oven, is difficult to realize industrialization production；3) disintegrant employs single low take
For hydroxypropyl cellulose, disintegration effect is not good, therefore selection low pressure tabletting, though tablet, which is made, can reach that disintegration time limited requires,
Because hardness is small, friability is often unqualified.
The content of the invention
It is an object of the invention to provide a kind of convenient to take, in good taste, bioavilability high salbutamol sulfate mouthful
Cavity disintegrating tablet and the process for preparing the disintegrated tablet.
The object of the present invention is achieved like this：A kind of salbutamol sulfate oral disnitegration tablet, includes the sulphur of effective dose
Auxiliary material is filler, flavouring, disintegrant, lubricant and bonding in auxiliary material on sour salbutamol and pharmacy, the pharmacy
Agent, it is characterised in that：The filler is mannitol and microcrystalline cellulose, and the flavouring is mannitol, and the disintegrant is
PVPP and low-substituted hydroxypropyl cellulose, the lubricant are silica and magnesium stearate, and described adhesive is purifying
Water, wherein each component are by weight percentage：
Wherein, the addition of adhesive purified water is mannitol, microcrystalline cellulose, 30~80% crosslinking of total addition
The 30%-40% of the gross weight of PVP and low-substituted hydroxypropyl cellulose.
Further, the consumption of the disintegrant PVPP and low-substituted hydroxypropyl cellulose is with weight ratio meter, to hand over
Join PVP: low-substituted hydroxypropyl cellulose=1:0.1~2.
Further, each component in the salbutamol sulfate oral disnitegration tablet is by weight percentage：Sulfuric acid is husky
Butylamine alcohol 0.9%, mannitol 62.5%, microcrystalline cellulose 15.6%, PVPP 10.2%, low-substituted hydroxypropyl cellulose
7.8%th, silica 2%, magnesium stearate 1%；In addition, the addition of adhesive purified water be mannitol, it is microcrystalline cellulose, total
The 35.9% of 50% PVPP of addition and the gross weight of low-substituted hydroxypropyl cellulose；I.e. using each component gross weight as
100g timing, the addition of adhesive purified water is [62.5+15.6+ (10.2+7.8) × 50%] × 35.9%=31.3g.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1, salbutamol sulfate mixed with silica, 120 mesh sieves were poured out, to mix powder I；Cross the purpose of 120 mesh sieves
It is that, in order to reduce the contact area of salbutamol sulfate and equipment, mitigation always mixes the viscosity of particle in sheeting process, it is to avoid tabletting
Glutinous punching, card rush phenomenon；
S2, by mannitol, microcrystalline cellulose, total addition 30~80% PVPP and low-substituted hydroxypropyl cellulose
It is well mixed, add stirred 20~40 mesh sieve series wet granular of purified water；The addition of the purified water is mannitol, crystallite fibre
The 30%-40% of the PVPP of plain, the total addition 30~80% of dimension and the gross weight of low-substituted hydroxypropyl cellulose；
S3, drying wet granular, the control wet granular drying temperature 60-90 DEG C of water content to particle are less than 3%, must do
Grain；
S4, dry particl cross 20~40 mesh sieves and carry out whole grain；
S5, the PVPP and low-substituted hydroxypropyl cellulose of surplus, magnesium stearate, mixed powder I be added to step S4 systems
Obtain and mixed in particle, obtain and always mix particle；Now add mixed powder I, it is to avoid drying process high temperature is to mixing the main ingredient in powder I
The influence of stability；
S6, calculate the theoretical tablet weight by total mixed granule content, tabletting is weighed；
S7, the qualified tablets of S6 are packed.
Further, the step S5, which always mixes particle, need to carry out moisture, active component content detection；
Further, adjustment sheet weight is 64mg/ pieces during tabletting in the step S6, is rushed using 5.5mm circular flats.
Further, the qualified salbutamol sulfate oral disnitegration tablet packagings of the step S7 use aluminum-plastic blister, the aluminium
Mould bubble-cap overcoat plastic-aluminum moisture barrier bag.
Further, the hardness range of the salbutamol sulfate oral disnitegration tablet is 1.0kgf~3.0kgf.
Present invention contrast prior art has following advantageous effects：1) present invention in disintegrant using combine by the way of,
There is disintegration effect well using single disintegrant compared with salbutamol sulfate, can significantly shorten the disintegration time limited of product；
2) adhesive in invention be purified water, make dry after grain forming it is good, substantially improve the mobility of salbutamol sulfate, press
Tablet weight variation is small during piece, has compared with other conventional binder PVP, sodium carboxymethylcellulose, hydroxypropyl methylcelluloses etc. more preferable
Effect is disintegrated, and water source is wide, cost is low；3) wet granulation technology is used, is efficiently solved based on the husky butylamine of bulk drug sulfuric acid
The problems such as tabletting sticking, card are rushed caused by alcohol self property, possesses the feasibility of production；4) it is dry in particle in the inventive method
Add the mixed powder of the salbutamol sulfate containing main ingredient after dry, it is to avoid influence of the dry high temperature to main ingredient stability, and impurity
Content is low；5) disintegrant is added portionwise in pelletization using " interior to add " and " additional ", using process so that disintegrant
It is uniformly dispersed in tablets, is more beneficial for being made difference between the homogeneity of product disintegration time limited of the present invention, piece small；6) present invention production
Product and method cost are low, and auxiliary material is common auxiliary material in salbutamol sulfate oral disnitegration tablet, and adhesive is water；Production
During process equipment it is simple, easy to implement the method and controllable, operating cost is low, economical, conveniently, can be mass-produced.
Embodiment
Embodiment 1
Prescription：
Wherein, the consumption of adhesive purified water is 12g, accounts for mannitol, microcrystalline cellulose, 50% crosslinking of total addition
The 21.5% of the gross weight of PVP and low-substituted hydroxypropyl cellulose.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
S2, by 40g mannitol, 10g microcrystalline celluloses, the PVPP of total addition 50% and low-substituted hydroxypropyl fiber
Element is well mixed, adds the stirred 30 mesh sieve series wet granular of 12g purified waters；
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the PVPP and low-substituted hydroxypropyl cellulose of surplus, 0.64g magnesium stearates, mixed powder I be added to step
S4 is made in particle and mixed, and obtains and always mixes particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer blind test masters
Taste and sweet mouthfeel is told, has lubrication to feel but without grittiness.Measure tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ±
6%, 24~42 seconds disintegration time limiteds.
Embodiment 2
Prescription：
Wherein, the consumption of adhesive purified water is 10kg, accounts for mannitol, microcrystalline cellulose, 50% friendship of total addition
Join the 35.9% of the gross weight of PVP and low-substituted hydroxypropyl cellulose.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.3kg salbutamol sulfates are mixed with 0.64kg silica, 120 mesh sieves were poured out, to mix powder I；
It is S2,20kg mannitol, 5kg microcrystalline celluloses, the PVPP of total addition 50% and low-substituted hydroxypropyl is fine
Dimension element is well mixed, adds the stirred 30 mesh sieve series wet granular of 10kg purified waters；
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the PVPP and low-substituted hydroxypropyl cellulose of surplus, 0.32kg magnesium stearates, mixed powder I be added to step
Rapid S4, which is made in particle, to be mixed, and is obtained and is always mixed particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 500000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 50 volunteer's blind tests
Main suit's taste and sweet mouthfeel, has lubrication to feel but without grittiness.Measure tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation
± 4%, 23~40 seconds disintegration time limiteds.All other indexs are qualified, and accelerated test investigates 6 months steady qualities.
Embodiment 3
Prescription：
Wherein, the consumption of adhesive purified water is 21.5g, accounts for mannitol, microcrystalline cellulose, 50% friendship of total addition
Join the 39.5% of the gross weight of PVP and low-substituted hydroxypropyl cellulose.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
It is S2,37.4g mannitol, 10g microcrystalline celluloses, the PVPP of total addition 50% and low-substituted hydroxypropyl is fine
Dimension element is well mixed, adds 21.5g purified water softwoods, softwood is crossed into 30 mesh sieve series wet granulars；
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the PVPP and low-substituted hydroxypropyl cellulose of surplus, 0.64g magnesium stearates, mixed powder I be added to step
S4 is made in particle and mixed, and obtains and always mixes particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer blind test masters
Taste and sweet mouthfeel is told, has lubrication to feel but without grittiness.Tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ± 3% collapses
Solve 26~44 seconds time limits.
Embodiment 4
Prescription：
Wherein, the consumption of adhesive purified water is 22g, accounts for mannitol, microcrystalline cellulose, 50% crosslinking of total addition
The 39.4% of the gross weight of PVP and low-substituted hydroxypropyl cellulose.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
S2, by 40g mannitol, 10g microcrystalline celluloses, the PVPP of total addition 50% and low-substituted hydroxypropyl fiber
Element is well mixed, adds 22g purified water softwoods, softwood is crossed into 30 mesh sieve series wet granulars；
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the PVPP and low-substituted hydroxypropyl cellulose of surplus, 0.64g magnesium stearates, mixed powder I be added to step
S4 is made in particle and mixed, and obtains and always mixes particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer blind test masters
Taste and sweet mouthfeel is told, has lubrication to feel but without grittiness.Tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ± 3% collapses
Solve 28~45 seconds time limits.
Embodiment 5
Prescription：
Wherein, the consumption of adhesive purified water is 21g, accounts for mannitol, microcrystalline cellulose, 50% low of total addition and takes
For the 37.7% of the gross weight of hydroxypropylcellulose.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
S2, the low-substituted hydroxypropyl cellulose of 40g mannitol, 10g microcrystalline celluloses, total addition 50% is well mixed,
21g purified water softwoods are added, softwood is crossed into 30 mesh sieve series wet granulars；
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the low-substituted hydroxypropyl cellulose of surplus, 0.64g magnesium stearates, mixed powder I be added to step S4 and be made in particle
Mixed, obtain and always mix particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer blind test masters
Taste and sweet mouthfeel is told, has lubrication to feel but without grittiness.Tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ± 4% collapses
Solve 54~68 seconds time limits.
Embodiment 6
Prescription：
Wherein, the consumption of adhesive purified water is 21g, accounts for mannitol, microcrystalline cellulose, 50% crosslinking of total addition
The 37.7% of the gross weight of PVP.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
S2, the PVPP of 40g mannitol, 10g microcrystalline celluloses, total addition 50% is well mixed, adds 21g
Purified water softwood, 30 mesh sieve series wet granulars are crossed by softwood；
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the PVPP of surplus, 0.64g magnesium stearates, mixed powder I be added to step S4 it be made in particle and mixed
Close, obtain and always mix particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer blind test masters
Taste and sweet mouthfeel is told, has lubrication to feel but without grittiness.Tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ± 4% collapses
Solve 45~64 seconds time limits.
Embodiment 7
Prescription：
Wherein, the consumption of adhesive purified water is 21g, accounts for mannitol, microcrystalline cellulose, 50% carboxylic first of total addition
The 37.7% of base sodium starch and the gross weight of low-substituted hydroxypropyl cellulose.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
It is S2,40g mannitol, 10g microcrystalline celluloses, the sodium carboxymethyl starch of total addition 50% and low-substituted hydroxypropyl is fine
Dimension element is well mixed, adds 21g purified water softwoods, softwood is crossed into 30 mesh sieve series wet granulars；
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose of surplus, 0.64g magnesium stearates, mixed powder I be added to step
Rapid S4, which is made in particle, to be mixed, and is obtained and is always mixed particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer blind test masters
Taste and sweet mouthfeel is told, has lubrication to feel but without grittiness.Tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ± 4% collapses
Solve 50~65 seconds time limits.
Embodiment 8
Prescription：
Wherein, the consumption of adhesive purified water is 21g, accounts for mannitol, microcrystalline cellulose, 50% carboxylic first of total addition
The 37.7% of base sodium starch and the gross weight of Ac-Di-Sol.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
It is S2,40g mannitol, 10g microcrystalline celluloses, the sodium carboxymethyl starch of total addition 50% and cross-linked carboxymethyl is fine
The plain sodium of dimension is well mixed, and adds 21g purified water softwoods, softwood is crossed into 30 mesh sieve series wet granulars；
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the sodium carboxymethyl starch and Ac-Di-Sol of surplus, 0.64g magnesium stearates, mixed powder I be added to
Step S4 is made in particle and mixed, and obtains and always mixes particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer blind test masters
Taste and sweet mouthfeel is told, has lubrication to feel but without grittiness.Tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ± 4% collapses
Solve 54~70 seconds time limits.
Embodiment 9
Prescription：
Wherein, the consumption of the PVP k30 aqueous solution of adhesive 5% is 12g, accounts for mannitol, microcrystalline cellulose, total addition
50% PVPP and low-substituted hydroxypropyl cellulose gross weight 21.5%.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
S2, by 40g mannitol, 10g microcrystalline celluloses, the PVPP of total addition 50% and low-substituted hydroxypropyl fiber
Element is well mixed, adds 5% PVP k30 aqueous solution 12g softwoods, softwood is crossed into 30 mesh sieve series wet granulars；Wherein 5% poly- dimension
The compound method of the ketone k30 aqueous solution is that stirring and dissolving in five parts of PVP k30 95 parts of purified waters of addition is complete, with parts by weight
Meter.
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the PVPP and low-substituted hydroxypropyl cellulose of surplus, 0.64g magnesium stearates, mixed powder I be added to step
S4 is made in particle and mixed, and obtains and always mixes particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer's blind tests mouthful
Sense is sweet, has lubrication to feel but without grittiness.Tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ± 4%, during disintegration
Limit>60 seconds.
Embodiment 10
Prescription：
Wherein, the consumption of the hydroxypropyl methylcellulose aqueous solution of adhesive 5% is 12g, accounts for mannitol, microcrystalline cellulose, always adds
Enter the 21.5% of 50% PVPP of amount and the gross weight of low-substituted hydroxypropyl cellulose.
A kind of preparation method of salbutamol sulfate oral disnitegration tablet, it is characterised in that comprise the steps：
S1,0.6g salbutamol sulfates are mixed with 1.28g silica, 120 mesh sieves were poured out, to mix powder I；
S2, by 40g mannitol, 10g microcrystalline celluloses, the PVPP of total addition 50% and low-substituted hydroxypropyl fiber
Element is well mixed, adds 5% hydroxypropyl methylcellulose aqueous solution 12g softwoods, softwood is crossed into 30 mesh sieve series wet granulars；Wherein 5%
The compound method of the hydroxypropyl methylcellulose aqueous solution is to add five parts of hydroxypropyl methylcelluloses in 50 parts of 60~80 DEG C of purified waters to stir
It is scattered, then add 45 parts of normal temperature purified water stirring and dissolvings completely, in parts by weight.
S3, drying wet granular, 80 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 30 mesh sieves and carry out whole grain；
S5, the PVPP and low-substituted hydroxypropyl cellulose of surplus, 0.64g magnesium stearates, mixed powder I be added to step
S4 is made in particle and mixed, and obtains and always mixes particle；
S6, detection always mix the indexs such as pellet moisture, content, are calculated the theoretical tablet weight by total mixed granule content, tabletting, tabletting is adopted
It is that 5.5mm circular flats are rushed with punch die；
S7, will be made qualified salbutamol sulfate oral disnitegration tablet aluminium-plastic bubble plate packing, overcoat plastic-aluminum moisture barrier bag.
Above-mentioned formula prepares 1000 altogether, and specification 64mg, tableting processes do not occur sticking situation, 5 volunteer's blind tests mouthful
Sense is sweet, has lubrication to feel but without grittiness.Tablet hardness 1.0-3.0kgf, friability 0.3%, tablet weight variation ± 4%, during disintegration
Limit>60 seconds.
The present inventor of table 1 different adhesive in each embodiment and its accounting, different disintegrants is made the hardness, crisp of sample
Broken degree, tablet weight variation and disintegration time limited are contrasted, such as following table：
It can draw to draw a conclusion from upper table：(1) accounting of the adhesive purified water of embodiment 1,2 and 3 increases successively, piece
Substantially, when purified water accounting is when between 30~40%, tablet weight variation is smaller by weight contrast difference；(2) in embodiment 2,3 and 4,
Smaller is influenceed on disintegration time limited as disintegrant PVPP and low-substituted hydroxypropyl cellulose weight ratio change, is satisfied by new
Requirement of the version pharmacopeia for disintegration time limited (within 1 minute)；(3) embodiment 2,5,6,7 and 8 discloses combination disintegrant crosslinking and gathered
Tie up ketone and the more single disintegrant PVPP of low-substituted hydroxypropyl cellulose, low-substituted hydroxypropyl fiber and other disintegrants combination tool
There is shorter disintegration time limited；(4) from embodiment 1,9 and 10 it can be seen that when binder is purified water, disintegration effect is best；(5)
Disintegrant is added portionwise in pelletization using " interior to add " and " additional ", using process so that disintegrant divides in tablets
Dissipate uniform, be more beneficial for difference between the homogeneity of product disintegration time limited of the present invention, piece small.
The following table of table 2 is the different total angles of repose mixed measured by particles of adhesives preparation in preparation method of the present invention：
| Embodiment | Adhesive | Ratio shared by adhesive | Angle of repose |
| 1 | Purified water | 21.5% | 35-36° |
| 2 | Purified water | 35.9% | 32-33° |
| 3 | Purified water | 39.5% | 31-32° |
| 4 | Purified water | 39.4% | 31-32° |
| 5 | Purified water | 37.7% | 32-33° |
| 6 | Purified water | 37.7% | 32-33° |
| 7 | Purified water | 37.7% | 32-33° |
| 8 | Purified water | 37.7% | 32-33° |
| 9 | The 5% PVP k30 aqueous solution | 21.5% | 32-33° |
| 10 | The 5% hydroxypropyl methylcellulose aqueous solution | 21.5% | 32-33° |
As can be seen from the table, the addition of adhesive purified water is when between 30~40%, and angle of repose is smaller, is made total
The mobility of mixed particle is preferable, it is easy to tabletting and tablet weight variation is small, compared with other PVP k30 aqueous solution of binder 5% and 5% hydroxyl
The third methylcellulose aqueous solution is in identical accounting, and disintegration time limited substantially shortens (such as upper table 1).
The specific embodiment of the present invention is the foregoing is only, is not intended to limit the invention, for the skill of this area
For art personnel, within the spirit and principles of the invention, any modification, equivalent substitution and improvements done etc. all should be included
Within protection scope of the present invention.
Claims (8)
1. a kind of salbutamol sulfate oral disnitegration tablet, including auxiliary material on the salbutamol sulfate and pharmacy of effective dose, institute
It is filler, flavouring, disintegrant, lubricant and adhesive to state auxiliary material in pharmacy, it is characterised in that：The filler is sweet
Reveal alcohol and microcrystalline cellulose, the flavouring is mannitol, and the disintegrant is PVPP and low-substituted hydroxypropyl cellulose
Combination, the lubricant be silica and magnesium stearate, described adhesive is purified water, wherein each component percentage by weight
Than being calculated as：
Wherein, the addition of adhesive purified water is mannitol, microcrystalline cellulose, the PVPP of total addition 30~80%
With the 30%-40% of the gross weight of low-substituted hydroxypropyl cellulose.
2. salbutamol sulfate oral disnitegration tablet as claimed in claim 1, it is characterised in that：The disintegrant PVPP
Consumption with low-substituted hydroxypropyl cellulose, with weight ratio meter, is PVPP: low-substituted hydroxypropyl cellulose=1:0.1~2.
3. salbutamol sulfate oral disnitegration tablet as claimed in claim 1, it is characterised in that：The salbutamol sulfate oral cavity
Each component in disintegrated tablet is by weight percentage：Salbutamol sulfate 0.9%, mannitol 62.5%, microcrystalline cellulose
15.6%th, PVPP 10.2%, low-substituted hydroxypropyl cellulose 7.8%, silica 2%, magnesium stearate 1%；In addition, viscous
The addition of mixture purified water is mannitol, microcrystalline cellulose, 50% PVPP and low-substituted hydroxypropyl of total addition
The 35.9% of the gross weight of cellulose；I.e. using each component gross weight as 100g timing, the addition of adhesive purified water is [62.5
+ 15.6+ (10.2+7.8) × 50%] × 35.9%=31.3g.
4. the preparation method of the salbutamol sulfate oral disnitegration tablet as described in any in claims 1 to 3, it is characterised in that：
Comprise the steps：
S1, salbutamol sulfate mixed with silica, 120 mesh sieves were poured out, to mix powder I；
S2, by mannitol, microcrystalline cellulose, the PVPP of total addition 30~80% and low-substituted hydroxypropyl cellulose mix
Uniformly, stirred 20~40 mesh sieve series wet granular of purified water is added；The addition of the purified water is mannitol, microcrystalline cellulose
The 30%-40% of the PVPP of plain, total addition 30~80% and the gross weight of low-substituted hydroxypropyl cellulose；
S3, drying wet granular, the 60-90 DEG C of water content to particle of control wet granular drying temperature are less than 3%, obtain dry particl；
S4, dry particl cross 20~40 mesh sieves and carry out whole grain；
S5, the PVPP and low-substituted hydroxypropyl cellulose of surplus, magnesium stearate, mixed powder I are added to step S4 are made
Mixed in grain, obtain and always mix particle；
S6, calculate the theoretical tablet weight by total mixed granule content, tabletting is weighed；
S7, the qualified tablets of step S6 are packed.
5. the preparation method of salbutamol sulfate oral disnitegration tablet as claimed in claim 4, it is characterised in that：The step S5
Always mixed particle need to carry out moisture, active component content detection.
6. the preparation method of salbutamol sulfate oral disnitegration tablet as claimed in claim 4, it is characterised in that：The step S6
Adjustment sheet weight is 6.4mg/ pieces during middle tabletting, is rushed using 5.5mm circular flats.
7. the preparation method of salbutamol sulfate oral disnitegration tablet as claimed in claim 4, it is characterised in that：, the step
S7 is qualified, and salbutamol sulfate oral disnitegration tablet packaging uses aluminum-plastic blister, the aluminum-plastic blister overcoat plastic-aluminum moisture barrier bag.
8. the preparation method of salbutamol sulfate oral disnitegration tablet as claimed in claim 4, it is characterised in that：, the sulfuric acid
The hardness range of salbutamol oral disnitegration tablet is 1.0kgf~3.0kgf.
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| CN111228227A (en) * | 2020-03-06 | 2020-06-05 | 重庆康刻尔制药有限公司 | Salbutamol sulfate oral disintegrating tablet and preparation method thereof |
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