CN106822045B - A kind of R-lansoprazole sustained release preparation and preparation method thereof and drug - Google Patents
A kind of R-lansoprazole sustained release preparation and preparation method thereof and drug Download PDFInfo
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- CN106822045B CN106822045B CN201710190699.6A CN201710190699A CN106822045B CN 106822045 B CN106822045 B CN 106822045B CN 201710190699 A CN201710190699 A CN 201710190699A CN 106822045 B CN106822045 B CN 106822045B
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- sustained release
- lansoprazole
- base ball
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
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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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
Abstract
The present invention provides a kind of R-lansoprazole sustained release preparation and preparation method thereof and drugs, R-lansoprazole sustained release preparation of the present invention has specific release structures, including base ball, separation layer and coatings are successively coated on the outside of the base ball, the base ball, special component is respectively adopted in separation layer and coatings and the raw material of dosage is prepared, the preparation of all kinds of medical drugs of gained R-lansoprazole sustained release preparation, particularly suitable for the preparation of capsule-type drug, it can be extensive after taking, it is evenly distributed in gastrointestinal tract, on stomach and intestine surface, distribution area is big, to improve bioavilability, reduce or eliminate stimulation of the drug to gastrointestinal tract, in the transhipment of gastrointestinal tract the rhythm and pace of moving things is not conveyed by food, the influence of gastric emptying, release the drug regular favorable reproducibility, mobility is preferable, be conducive to preparation packing.The preparation method simple process of R-lansoprazole sustained release preparation of the present invention, variance factor is small, and quality is controllable, is suitable for large-scale production.
Description
Technical field
The present invention relates to slow releasing pharmaceutical technical fields, in particular to a kind of R-lansoprazole sustained release preparation and its system
Preparation Method and drug.
Background technique
R-lansoprazole is proton pump inhibitor.Proton pump inhibitor is benzimidazoles derivative, specific and non-competing
Striving property acts on H+/K+ATP enzyme treats peptic ulcer.Proton pump inhibitor is mostly fat-soluble alkalescent, after absorbed into serum
Into after acidic environment in parietal cell secretory tubyle, small envelope chamber, activation products are generally active sulfenic acids and sulfenamide, with
H+- K+ATP enzyme sulfydryl is coupled to form an irreversible covalent disulfide bonds, blocks H+- K+Transporting mechanism, to inhibit stomach
Acid secretion.
In the related technology, proton pump inhibitor medicament slow release ability is limited, cannot play drug effect for a long time, in the gastrointestinal tract
It is unable to fine dispersion, big to the stimulation of gastrointestinal tract, bioavilability is low, and the drug effect receipts food conveying rhythm and pace of moving things, the influence of gastric emptying are big,
Release the drug regular poor reproducibility, limited efficacy.
In view of this, the present invention is specifically proposed.
Summary of the invention
The first object of the present invention is to provide a kind of R-lansoprazole sustained release preparation, the R-lansoprazole sustained release system
Agent can extensively, be evenly distributed in gastrointestinal tract, on stomach and intestine surface, distribution area is big, thus improve bioavilability, reduce or
Stimulation of the drug to gastrointestinal tract is eliminated, is not influenced by the food conveying rhythm and pace of moving things, gastric emptying in the transhipment of gastrointestinal tract, the rule that releases the drug weight
Existing property is good, and mobility is preferable, is conducive to preparation packing.
The second object of the present invention is to provide the preparation method of R-lansoprazole sustained release preparation described in one kind, this method
Simple process, variance factor is small, and quality is controllable, is suitable for large-scale production.
The third object of the present invention is to provide a kind of drug comprising the R-lansoprazole sustained release preparation, described
R-lansoprazole sustained release preparation can be used for the preparation of all kinds of medical drugs, particularly suitable for the preparation of capsule-type drug, energy after taking
Enough extensively, it is evenly distributed in gastrointestinal tract, distribution area is big on stomach and intestine surface, to improve bioavilability, reduce or eliminate
Stimulation of the drug to gastrointestinal tract is not influenced in the transhipment of gastrointestinal tract by the food conveying rhythm and pace of moving things, gastric emptying, and release the drug regular reproducibility
Good, drug effect is significant.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
A kind of R-lansoprazole sustained release preparation, the R-lansoprazole sustained release preparation include base ball, packet on the outside of the base ball
Separation layer is covered, coats coatings on the outside of the separation layer；
The base ball is mainly prepared by the raw material of following mass fraction:
150-450 parts of R-lansoprazole, 50-150 parts of base ball disintegrating agent, 200-600 parts of base ball adhesive, diluent 100-
200 parts and 50-100 parts of pH regulating stabilizer；
The separation layer is mainly prepared by the raw material of following mass fraction:
Anti- even agent 15-45 parts and 10-20 parts of separation layer auxiliary agent of 50-100 parts of separation layer adhesive, separation layer；
The coatings include following coatings A and/or coatings B, preferably include coatings A and coatings B；
The coatings A is mainly prepared by the raw material of following mass fraction:
50-100 parts of slow-release material, 2-6 parts of regulator, 10-20 parts of solubilizer, 30-70 parts of plasticizer, coatings auxiliary agent 4-
12 parts and anti-even agent 15-45 parts of coatings；
The coatings B is mainly prepared by the raw material of following mass fraction:
150-300 parts of slow-release material, 6-18 parts of regulator, 30-60 parts of solubilizer, 100-200 parts of plasticizer, coatings help
12-36 parts of agent anti-even agent 60-120 parts with coatings.
R-lansoprazole sustained release preparation of the present invention has specific release structures, including base ball, successively wraps on the outside of the base ball
Separation layer and coatings are covered, special component is respectively adopted in the base ball, separation layer and coatings and the raw material of dosage is prepared,
Gained R-lansoprazole sustained release preparation can extensively, be evenly distributed in gastrointestinal tract, on stomach and intestine surface, distribution area is big, to mention
High bioavilability reduces or eliminates stimulation of the drug to gastrointestinal tract, is not arranged by the food conveying rhythm and pace of moving things, stomach in the transhipment of gastrointestinal tract
Empty influence, release the drug regular favorable reproducibility, and mobility is preferable, is conducive to preparation packing.
Optionally, the base ball is mainly prepared by the raw material of following mass fraction:
200-400 parts of R-lansoprazole, 80-120 parts of base ball disintegrating agent, 300-500 parts of base ball adhesive, diluent 120-
180 parts and 70-90 parts of pH regulating stabilizer.
Preferably, the base ball is mainly prepared by the raw material of following mass fraction:
300 parts of R-lansoprazole, 100 parts of base ball disintegrating agent, 420 parts of base ball adhesive, 155 parts of diluent and pH adjust steady
Determine 85 parts of agent.
Optionally, the separation layer is mainly prepared by the raw material of following mass fraction:
Anti- even agent 20-40 parts and 12-18 parts of separation layer auxiliary agent of 70-90 parts of separation layer adhesive, separation layer.
Preferably, the separation layer is mainly prepared by the raw material of following mass fraction:
80 parts of separation layer adhesive, separation layer are anti-to connect 30 parts of agent and 15 parts of separation layer auxiliary agent.
Optionally, the coatings A is mainly prepared by the raw material of following mass fraction:
70-80 parts of slow-release material, 3-5 parts of regulator, 12-18 parts of solubilizer, 40-60 parts of plasticizer, coatings auxiliary agent 6-
10 parts and anti-even agent 20-40 parts of coatings.
Preferably, the coatings A is mainly prepared by the raw material of following mass fraction:
75 parts of slow-release material, 4 parts of regulator, 15 parts of solubilizer, 50 parts of plasticizer, 8 parts of coatings auxiliary agent and coatings are anti-
Even 30 parts of agent.
Optionally, the coatings B is mainly prepared by the raw material of following mass fraction:
200-250 parts of slow-release material, 9-15 parts of regulator, 40-50 parts of solubilizer, 120-180 parts of plasticizer, coatings help
18-30 parts of agent anti-even agent 80-100 parts with coatings.
Preferably, the coatings B is mainly prepared by the raw material of following mass fraction:
225 parts of slow-release material, 12 parts of regulator, 45 parts of solubilizer, 150 parts of plasticizer, 24 parts of coatings auxiliary agent and coating
Anti- even 90 parts of agent of layer.
Optionally, the quantity ratio of the coatings A and coatings B is 1:1-5, preferably 1:2-4, further preferably 1:
3。
Optionally, the base ball disintegrating agent includes sodium carboxymethyl starch, hydroxypropyl cellulose, crosslinked polyethylene pyrrolidines
One of ketone, gas-producing disintegrant and sodium carboxymethylcellulose are a variety of, preferably include sodium carboxymethylcellulose.
Optionally, the base ball adhesive includes one or both of sucrose and dextrin, preferably includes sucrose and dextrin.
Optionally, the diluent includes starch.
Optionally, the pH regulating stabilizer includes sodium carbonate, preferably includes natrium carbonicum calcinatum.
Optionally, the separation layer adhesive includes hypromellose.
Optionally, the anti-even agent of the separation layer includes talcum powder.
Optionally, the separation layer auxiliary agent includes brightening agent.
Preferably, the brightening agent includes titanium dioxide.
Optionally, the slow-release material includes one of methacrylic resin copolymer and polyacrylic resin or two
Kind, preferably include methacrylic resin copolymer L100 or Eudragit S 100.
Optionally, the regulator includes polyethylene glycol, preferably includes Macrogol 6000.
Optionally, the solubilizer includes tween, preferably includes Tween 80.
Optionally, the plasticizer includes triethyl citrate.
Optionally, the coatings auxiliary agent includes brightening agent.
Preferably, the brightening agent includes titanium dioxide.
Optionally, the anti-even agent of the coatings includes talcum powder.
A kind of preparation method of above-mentioned R-lansoprazole sustained release preparation is granulated, in gained base after mixing base ball raw material
Ball surface coats separation layer, coats coatings in the insulation surface for the base ball for being coated with separation layer, obtains a kind of right Lan Suola
Azoles sustained release preparation.
The preparation method simple process of R-lansoprazole sustained release preparation of the present invention, variance factor is small, and quality is controllable, is suitable for big
Large-scale production.
Optionally, it is granulated in the granulation process using water or syrup.
Optionally, the syrup is aqueous sucrose solution.
Preferably, the mass fraction of the aqueous sucrose solution is 25%.
Optionally, solvent is used during the cladding separation layer.
Preferably, the solvent includes one or both of second alcohol and water.
Optionally, solvent is used during the cladding coatings.
Preferably, the solvent includes one or both of second alcohol and water.
Drug comprising a kind of above-mentioned R-lansoprazole sustained release preparation.
Optionally, the drug includes capsule pharmaceutical.
R-lansoprazole sustained release preparation of the present invention can be used for the preparation of all kinds of medical drugs, particularly suitable for capsule-type drug
Preparation, after taking can extensively, be evenly distributed in gastrointestinal tract, on stomach and intestine surface, distribution area is big, to improve biological utilisation
The stimulation spent, reduce or eliminate drug to gastrointestinal tract is not influenced in the transhipment of gastrointestinal tract by the food conveying rhythm and pace of moving things, gastric emptying,
Release the drug regular favorable reproducibility, and drug effect is significant.
Compared with prior art, the invention has the benefit that
R-lansoprazole sustained release preparation of the present invention has specific release structures, including base ball, successively wraps on the outside of the base ball
Separation layer and coatings are covered, special component is respectively adopted in the base ball, separation layer and coatings and the raw material of dosage is prepared,
The preparation of all kinds of medical drugs of gained R-lansoprazole sustained release preparation can after taking particularly suitable for the preparation of capsule-type drug
Extensively, it is evenly distributed in gastrointestinal tract, distribution area is big on stomach and intestine surface, to improve bioavilability, reduce or eliminate medicine
Stimulation of the object to gastrointestinal tract is not influenced in the transhipment of gastrointestinal tract by the food conveying rhythm and pace of moving things, gastric emptying, and release the drug regular reproducibility
Good, mobility is preferable, is conducive to preparation packing.The preparation method simple process of R-lansoprazole sustained release preparation of the present invention, variation
Factor is small, and quality is controllable, is suitable for large-scale production.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with specific embodiment, but ability
Field technique personnel will be understood that following described embodiments are some of the embodiments of the present invention, instead of all the embodiments,
It is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.Based on the embodiments of the present invention, the common skill in this field
Art personnel every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.The person that is not specified actual conditions in embodiment, carries out according to conventional conditions or manufacturer's recommended conditions.Agents useful for same or instrument
Production firm person is not specified, is the conventional products that can be obtained by commercially available purchase.
The present invention provides a kind of R-lansoprazole sustained release preparation, the R-lansoprazole sustained release preparation includes base ball, institute
It states and coats separation layer on the outside of base ball, coat coatings on the outside of the separation layer；
The base ball is mainly prepared by the raw material of following mass fraction:
150-450 parts of R-lansoprazole, 50-150 parts of base ball disintegrating agent, 200-600 parts of base ball adhesive, diluent 100-
200 parts and 50-100 parts of pH regulating stabilizer；
The separation layer is mainly prepared by the raw material of following mass fraction:
Anti- even agent 15-45 parts and 10-20 parts of separation layer auxiliary agent of 50-100 parts of separation layer adhesive, separation layer；
The coatings include following coatings A and/or coatings B, preferably include coatings A and coatings B；
The coatings A is mainly prepared by the raw material of following mass fraction:
50-100 parts of slow-release material, 2-6 parts of regulator, 10-20 parts of solubilizer, 30-70 parts of plasticizer, coatings auxiliary agent 4-
12 parts and anti-even agent 15-45 parts of coatings；
The coatings B is mainly prepared by the raw material of following mass fraction:
150-300 parts of slow-release material, 6-18 parts of regulator, 30-60 parts of solubilizer, 100-200 parts of plasticizer, coatings help
12-36 parts of agent anti-even agent 60-120 parts with coatings.
R-lansoprazole sustained release preparation of the present invention has specific release structures, including base ball, successively wraps on the outside of the base ball
Separation layer and coatings are covered, special component is respectively adopted in the base ball, separation layer and coatings and the raw material of dosage is prepared,
Gained R-lansoprazole sustained release preparation can extensively, be evenly distributed in gastrointestinal tract, on stomach and intestine surface, distribution area is big, to mention
High bioavilability reduces or eliminates stimulation of the drug to gastrointestinal tract, is not arranged by the food conveying rhythm and pace of moving things, stomach in the transhipment of gastrointestinal tract
Empty influence, release the drug regular favorable reproducibility, and mobility is preferable, is conducive to preparation packing.
In a kind of preferred embodiment of the present invention, the base ball is mainly prepared by the raw material of following mass fraction
It arrives:
200-400 parts of R-lansoprazole, 80-120 parts of base ball disintegrating agent, 300-500 parts of base ball adhesive, diluent 120-
180 parts and 70-90 parts of pH regulating stabilizer.
Preferably, the base ball is mainly prepared by the raw material of following mass fraction:
300 parts of R-lansoprazole, 100 parts of base ball disintegrating agent, 420 parts of base ball adhesive, 155 parts of diluent and pH adjust steady
Determine 85 parts of agent.
Base ball is prepared using the raw material of special component and dosage, gained R-lansoprazole sustained release preparation can be effectively improved,
Its stability under non-neutral pH environment is helped to improve, when base ball discharges, drug effect can be played rapidly, improve biological utilisation
Degree.
In a kind of preferred embodiment of the present invention, the separation layer is mainly prepared by the raw material of following mass fraction
It obtains:
Anti- even agent 20-40 parts and 12-18 parts of separation layer auxiliary agent of 70-90 parts of separation layer adhesive, separation layer.
Preferably, the separation layer is mainly prepared by the raw material of following mass fraction:
80 parts of separation layer adhesive, separation layer are anti-to connect 30 parts of agent and 15 parts of separation layer auxiliary agent.
Separation layer is prepared using the raw material of special component and dosage, can effective protection base ball, prevent base ball ingredient and packet
Clothing composition of layer reacts, while reducing drug migration phenomenon, avoids the sustained release and medicinal effects that influence gained drug.
In a kind of preferred embodiment of the present invention, the coatings A is mainly by the raw material system of following mass fraction
It is standby to obtain:
70-80 parts of slow-release material, 3-5 parts of regulator, 12-18 parts of solubilizer, 40-60 parts of plasticizer, coatings auxiliary agent 6-
10 parts and anti-even agent 20-40 parts of coatings.
Preferably, the coatings A is mainly prepared by the raw material of following mass fraction:
75 parts of slow-release material, 4 parts of regulator, 15 parts of solubilizer, 50 parts of plasticizer, 8 parts of coatings auxiliary agent and coatings are anti-
Even 30 parts of agent.
In a kind of preferred embodiment of the present invention, the coatings B is mainly by the raw material system of following mass fraction
It is standby to obtain:
200-250 parts of slow-release material, 9-15 parts of regulator, 40-50 parts of solubilizer, 120-180 parts of plasticizer, coatings help
18-30 parts of agent anti-even agent 80-100 parts with coatings.
Preferably, the coatings B is mainly prepared by the raw material of following mass fraction:
225 parts of slow-release material, 12 parts of regulator, 45 parts of solubilizer, 150 parts of plasticizer, 24 parts of coatings auxiliary agent and coating
Anti- even 90 parts of agent of layer.
Coatings are prepared using special component and the raw material of dosage, the sustained release performance of gained drug can be effectively controlled, subtract
Stimulation small or that elimination drug is to gastrointestinal tract is not influenced by the food conveying rhythm and pace of moving things, gastric emptying, drug release rule in the transhipment of gastrointestinal tract
Restrain favorable reproducibility.
Between each mass fraction of the present invention, every part of quality difference is equal.
In a kind of preferred embodiment of the present invention, the quantity ratio of the coatings A and coatings B are 1:1-5, excellent
It is selected as 1:2-4, further preferably 1:3.
It uses different coatings to be applied in combination with special ratios, helps that gained drug is made to form specific sustained release rule
Rule sufficiently avoids all drugs from concentrating drug release, effectively reduces or eliminate stimulation of the drug to gastrointestinal tract, while can also extend gained
The effective time of drug.
In a kind of preferred embodiment of the present invention, the base ball disintegrating agent includes sodium carboxymethyl starch, hydroxypropyl
One of cellulose, crosslinked polyvinylpyrrolidone, gas-producing disintegrant and sodium carboxymethylcellulose are a variety of, preferably include carboxylic
Sodium carboxymethylcellulose pyce.
In a kind of preferred embodiment of the present invention, the base ball adhesive include one of sucrose and dextrin or
Two kinds, preferably include sucrose and dextrin.
In a kind of preferred embodiment of the present invention, the diluent includes starch.
In a kind of preferred embodiment of the present invention, the pH regulating stabilizer includes sodium carbonate, preferably includes nothing
Aqueous sodium carbonate.
Base ball is prepared using specific raw material, gained R-lansoprazole sustained release preparation can be effectively improved, helped to improve
Its stability under non-neutral pH environment when base ball discharges, can play rapidly drug effect, improve bioavilability.
In a kind of preferred embodiment of the present invention, the separation layer adhesive includes hypromellose.
In a kind of preferred embodiment of the present invention, the anti-even agent of the separation layer includes talcum powder.
In a kind of preferred embodiment of the present invention, the separation layer auxiliary agent includes brightening agent.
Preferably, the brightening agent includes titanium dioxide.
Separation layer is prepared using specific raw material, can effective protection base ball, prevent base ball ingredient and coating composition of layer hair
Raw reaction, while drug migration phenomenon is reduced, avoid the sustained release and medicinal effects that influence gained drug.
In a kind of preferred embodiment of the present invention, the slow-release material include methacrylic resin copolymer and
One or both of polyacrylic resin preferably includes methacrylic resin copolymer L100 or polyacrylic resin
S100。
In a kind of preferred embodiment of the present invention, the regulator includes polyethylene glycol, preferably includes poly- second two
Alcohol 6000.
In a kind of preferred embodiment of the present invention, the solubilizer includes tween, preferably includes Tween 80.
In a kind of preferred embodiment of the present invention, the plasticizer includes triethyl citrate.
In a kind of preferred embodiment of the present invention, the coatings auxiliary agent includes brightening agent.
Preferably, the brightening agent includes titanium dioxide.
In a kind of preferred embodiment of the present invention, the anti-even agent of the coatings includes talcum powder.
Coatings are prepared using specific raw material, the sustained release performance of gained drug can be effectively controlled, reduce or eliminate medicine
Stimulation of the object to gastrointestinal tract is not influenced in the transhipment of gastrointestinal tract by the food conveying rhythm and pace of moving things, gastric emptying, and release the drug regular reproducibility
It is good.
A kind of preparation method of above-mentioned R-lansoprazole sustained release preparation is granulated, in gained base after mixing base ball raw material
Ball surface coats separation layer, coats coatings in the insulation surface for the base ball for being coated with separation layer, obtains a kind of right Lan Suola
Azoles sustained release preparation.
The preparation method simple process of R-lansoprazole sustained release preparation of the present invention, variance factor is small, and quality is controllable, is suitable for big
Large-scale production.
In a kind of preferred embodiment of the present invention, water or syrup is used to carry out in the granulation process as liquid phase
It is granulated.
In a kind of preferred embodiment of the present invention, the syrup is aqueous sucrose solution.
Preferably, the mass fraction of the aqueous sucrose solution is 25%.
In a kind of preferred embodiment of the present invention, solvent is used during the cladding separation layer.
Preferably, the solvent includes one or both of second alcohol and water.
In a kind of preferred embodiment of the present invention, solvent is used during the cladding coatings.
Preferably, the solvent includes one or both of second alcohol and water.
Liquid phase solvent used in the present invention etc. be illustrate dosage raw material be it is enough, these raw materials can be by subsequent
Drying process removal, it is believed that on product quality without influence.
Following steps progress can be used in the preparation method of R-lansoprazole sustained release preparation of the present invention:
(1) prepared by base ball:
It takes the raw material of base ball used to crush, is sieved, is sufficiently mixed respectively；
It takes gained mixed powder to be added in centrifugation pellet processing machine in right amount, covers cover, open air blower, exhaust blower starts compacted
Dynamic pump, makes liquid phase circulation, starts host, and turntable frequency is arranged, to be suitable for that feed flow frequency sprays into liquid phase, to dustless in pellet processing machine
Afterwards, slow down feed flow frequency, after producing master batch, release material sieving；
It takes master batch to be put into pellet processing machine, repeats aforesaid operations, amplify master batch, release material, sieving；
The wet ball sieved is dried, it is dry, it discharges after capsule core is dry, pellet after drying is sieved, qualification is obtained
Base ball.
(2) prepared by separation layer:
Qualified base ball is set in fluidized-bed coating machine, coating electromechanical source is opened, adjusts blower frequency, inlet air temperature is set,
Pill is preheated, when temperature of charge stabilization in certain temperature, starts to spray into isolating layer material liquid, adjusts hydrojet frequency, is sprayed
Pressure controls material preference temperature, from sampling hole random observation, adjusts feed flow frequency and blower frequency, have pellet must not viscous
Even, hydrojet terminates, dry, after drying, closes heating, discharging is shut down in cooling；
(3) prepared by coatings:
Above-mentioned coated pellet is set in fluidized-bed coating machine, coating electromechanical source is opened, adjusts blower frequency, setting air inlet temperature
Degree, pill is preheated, and is stablized when temperature of charge in certain temperature, starts to spray into coatings material liquid, adjusts hydrojet frequency, spray
Mist pressure controls material preference temperature, from sampling hole random observation, adjusts feed flow frequency and blower frequency, there is pellet must not
Adhesion, it is dry after waiting predetermined clothing liquid to be finished, after drying, heating is closed, discharging is shut down in cooling；
Examine: semi-finished product character, moisture, pellet content are (with C16H14F3N3O2S meter), coating weight gain, as a result should all meet
Regulation.
Mixed ball: two kinds of pellet A balls for wrapping different coatings and B ball are launched in proportion, are uniformly mixed.
(4) capsule charge:
Suitable number capsule is selected to be filled.During this, preparing for drug containing base ball is relatively easy, and selection is suitable auxiliary
Material is diluent, and after mixing, spray is centrifuged pill with suitable liquid phase；Packet separation layer be according to common process needs,
To reduce drug migration phenomenon, coatings and for a long time coating and the influence of storage China and foreign countries bound pair base ball are avoided；Coatings
It is prepared as the key of this product technique, the mainly weight gain of coatings and composition will generate different influences to release.
Drug comprising a kind of above-mentioned R-lansoprazole sustained release preparation.
In a kind of preferred embodiment of the present invention, the drug includes capsule pharmaceutical.
R-lansoprazole sustained release preparation of the present invention can be used for the preparation of all kinds of medical drugs, particularly suitable for capsule-type drug
Preparation, after taking can extensively, be evenly distributed in gastrointestinal tract, on stomach and intestine surface, distribution area is big, to improve biological utilisation
The stimulation spent, reduce or eliminate drug to gastrointestinal tract is not influenced in the transhipment of gastrointestinal tract by the food conveying rhythm and pace of moving things, gastric emptying,
Release the drug regular favorable reproducibility, and drug effect is significant.
Various embodiments of the present invention contain the preparation method of the capsule pharmaceutical of R-lansoprazole sustained release preparation in accordance with the following steps
It carries out:
1, preprocessing raw material and auxiliary material: crushed 100 mesh for sucrose, natrium carbonicum calcinatum respectively, and R-lansoprazole raw material crosses 120
Mesh, other auxiliary materials respectively cross 100 mesh after it is spare.
2, it ingredient and mixes: first checking for and correct and weigh utensil and accurately weighed respectively by recipe quantity after meeting the requirements
Each supplementary material, weighing must be checked by special messenger, and be recorded in time.
R-lansoprazole raw material and starch, dextrin, Icing Sugar and other recipe quantities are weighed respectively by base ball recipe quantity (30,000)
Auxiliary material, be uniformly mixed, it is stand-by to mix 60 minutes.
3, the preparation for the syrup that mass fraction is 25%:
It weighs sucrose (being not counted in base ball raw material dosage) to be added to the water, stirring is allowed to dissolve, and is put into jacketed pan and adds
Heat to boil, pour into stainless steel barrel put it is spare after cool.
4, mother is played:
It takes mixed powder to be about added in coating granulator, covers cover, open air blower, frequency sets 15hz, the row of opening
Dirt machine after checking that spray gun is normal, starts peristaltic pump, starts host, revolving speed 200-400 simultaneously dust cleaning machine air door pass to minimum
Rev/min, while the syrup that mass fraction is 25% is sprayed, it 8-15 revs/min of wriggling revolution speed, opens, after producing master batch, puts
Material out, and material is crossed into 40,60 meshes.
5, amplify:
After cleaning host, air blower drying is started, the master batch of 40-60 mesh is taken to be put into pot, opens dust cleaning machine, air door is beaten
It opens, remaining mixed powder is put into powder supply machine, start host, revolving speed is 300-700 revs/min, the syrup that spray mass fraction is 25%,
The powder supply after master batch is wet guarantees that starch ratio keeps pellet humidity suitable, when master batch being made to be amplified to about 30-40 mesh, releases material,
Cross 30,40 meshes.It takes the master batch of 30-40 mesh to repeat aforesaid operations, master batch is made to be amplified to about 20-30 mesh, release material, cross 18,
30 meshes.
It is dry: the wet ball sieved is put into vacuum oven, circulating water temperature control at 55 ± 5 DEG C, vacuum degree is greater than-
It 0.075Mpa drying time 4-5 hours, discharges after capsule core is dry.
It selects ball: pellet after drying being crossed into 18 mesh and 30 meshes ,+30 mesh of -18 mesh is qualified base ball.
The pellet made should meet claimed below: character should be the piller of white or off-white color；Moisture answers≤3.0%；It is micro-
Ball content is (with C16H14F3N3O2S meter) it should be 25%-28%.
Granularity: take the summation of 18 mesh screenings and 30 mesh oversizes that must not be lower than test sample 95%.
Intermediate station is handed over after satisfactory dry base ball is counted, sieve mesh number substandard product is handed at intermediate station waiting
Reason.
6, packet separation layer:
Separation layer River Bank Stability: hydroxypropyl methylcellulose is weighed by separation layer recipe quantity (30,000), is added in ethyl alcohol, stirs companion
Water is added after uniformly, adds titanium dioxide and stirs evenly, about 15 minutes, until completely dissolved, add talcum powder, stirs evenly stand-by.
Got from intermediate station and examine qualified base ball, and check the name of an article, lot number, specification, weight, inspection report etc..
Qualified base ball is set in fluidized-bed coating machine, open coating electromechanical source, adjust blower frequency 20-40Hz, be arranged into
50-60 DEG C of air temperature, pill is preheated, when leaving air temp is stablized at 45-50 DEG C, starts to spray into isolating layer material liquid, hydrojet
Frequency 5-20Hz, atomisation pressure 0.20-0.35Mpa control 45-50 DEG C of leaving air temp；From sampling hole grab sample, adjust
Feed flow frequency and blower frequency, make pellet that must not have adhesion, and if any adhesion, hard stop is simultaneously sieved, and whenabouts are 2 hours.
Hydrojet terminates, 20-30 minutes dry, controls 45-50 DEG C of leaving air temp.After drying, heating is closed, is cooled to
35 DEG C or less shutdown dischargings.
Spacer layer coating terminates sampling and checked: character should be the piller of white or off-white color；Moisture answers≤3.0%；
Pellet content is (with C16H14F3N3O2S meter) it should be 22%-25%, it as a result should all meet regulation.
7, packet coatings A:
The preparation of (1/4 isolation pellet amount) coatings A: Eudragit L100 100 is weighed by coatings A prescription, is gathered
Ethylene glycol 6000, triethyl citrate are dissolved in ethyl alcohol, in water mixed liquid, place 12 hours or more, the other auxiliary of recipe quantity is added
Material: Tween-80, titanium dioxide, talcum powder cross colloid mill, stir evenly stand-by.
Above-mentioned coated pellet (total isolation ball 1/4) is set in fluidized-bed coating machine, coating electromechanical source is opened, adjusts blower frequency
20-40Hz is arranged 50-60 DEG C of inlet air temperature, pill is preheated, and when temperature of charge is stablized at 45-50 DEG C, starts to spray into coating
Layer A material liquid, hydrojet frequency 5-30Hz, atomisation pressure 0.20-0.35Mpa control 39-45 DEG C of leaving air temp；From sampling hole with
Machine sampling observation, adjusts feed flow frequency and blower frequency, makes pellet that must not have adhesion, and if any adhesion, hard stop is simultaneously sieved, packet
The clothing time about 4 hours.
Hydrojet terminates, 20-30 minutes dry, controls 45-50 DEG C of leaving air temp.After drying, heating is closed, is cooled to
35 DEG C or less shutdown dischargings.
Coating terminates sampling and checked: character should be the piller of white or off-white color；Moisture answers≤3.0%: pellet contains
Amount is (with C16H14F3N3O2S meter) should be 15%~17%, burst size should be not greater than 10% in acid, releasing in pH of buffer 7.0
High-volume in 10 minutes, 20 minutes and 40 minutes sample points, 60%, 80%, the 90% of labelled amount should be not less than, as a result should all be met
Regulation.
It is attached: coating weight gain calculation formula: (slow release layer pellet weight-separation layer pellet weight)/separation layer pellet weight *
100%
The pellet being coated is contained in clean container and is sealed, material card is filled in and indicates the name of an article, specification, lot number, again
Amount etc..
8, packet coatings B:
The preparation of (3/4 isolation pellet amount) coatings B: polyacrylic acid resin S100, poly- second are weighed by coatings B recipe quantity
Glycol 6000, triethyl citrate are dissolved in ethyl alcohol, in water mixed liquid, place 12 hours or more, other auxiliary materials of recipe quantity are added:
Tween-80, titanium dioxide element, talcum powder cross colloid mill, stir evenly stand-by.
Above-mentioned coated pellet (total isolation ball 3/4) is set in fluidized-bed coating machine, coating electromechanical source is opened, adjusts blower frequency
20-40Hz is arranged 50-60 DEG C of inlet air temperature, pill is preheated, and when temperature of charge is stablized at 45-50 DEG C, starts to spray into coating
Layer B material liquid, hydrojet frequency 5-30Hz, atomisation pressure 0.20-0.35Mpa control 39-45 DEG C of leaving air temp；From sampling hole with
Machine sampling observation, adjusts feed flow frequency and blower frequency, makes pellet that must not have adhesion, and if any adhesion, hard stop is simultaneously sieved, packet
The clothing time about 4 hours.
Hydrojet terminates, 20-30 minutes dry, controls 45-50 DEG C of leaving air temp.After drying, heating is closed, is cooled to
35 DEG C or less shutdown dischargings.
Coating terminates sampling and checked: character should be the piller of white or off-white color；Moisture answers≤3.0%: pellet contains
Amount is (with C16H14F3N3O2S meter) should be 15%~17%, burst size should be less than 10% in acid, the burst size in pH of buffer 7.0
105 minutes, 1% should be cannot be less than, cannot be less than 20% at 140 minutes, should distinguish 160 minutes and 180 minutes sample points
For 50% and 80%, regulation as a result should all be met.
It is attached: coating weight gain calculation formula: (slow release layer pellet weight-separation layer pellet weight)/separation layer pellet weight *
100%
The pellet being coated is contained in clean container and is sealed, material card is filled in and indicates the name of an article, specification, lot number, again
Amount etc..
9, it mixes
It takes two kinds of coating micro-pills of A, B to be put into three-dimensional mixer in proportion, mixes, respectively in incorporation time about 5,10,15
Inspection by sampling after minute, character should be the piller of white or off-white color；Moisture answers≤3.0%；Pellet content (with
C16H14F3N3O2S meter) should be 15.0%~17%, burst size is not greater than the 10% of labelled amount in acid, releases in pH of buffer 7.0
High-volume it should be not less than 15%, 20%, the 22% of labelled amount 10 minutes, 20 minutes, 105 minutes；It should be no more than mark at 120 minutes
The 40% of the amount of showing；At 140 minutes, at 160 minutes, 180 minutes when should be not less than labelled amount 40%, 55% and 80%, should accord with
Close regulation.
10, capsule charge
The name of an article, specification, the lot number, weight of attal are wanted in verification, and check hollow softgel shell specification, quantity whether with technique
It is required that consistent.Select the filling mold of No. 2 (specification: 30mg) capsules.
Theoretical content object weight is calculated according to the content of pellet；
Calculation formula are as follows: theoretical content object weight=labelled amount/pellet content
Content uniformity :≤± 10%；
It is operated by " capsule filler standard practice instructions ", checks whether filling machine operating is normal, after machine is normal, be added
It wants pack grain and hollow rubber shell to start to fill test-run a machine, manufactures experimently out a little capsule, and detect capsule to inspection of semifinished product personnel
Content uniformity, average loading amount, character, content, release etc. start formal filling after meeting the requirements.
In stowing operation, control filling rate is 400-800/minute.The primary averagely grain of operative employee every 15 minutes records
Weight, average grain are controlled again in ± 10% range of theoretical grain weight.
Capsule charge terminates sampling and checked: character should be hard capsule, and content is white or off-white color piller；Loading amount
Difference≤± 7.0%, content are (with C16H14F3N3O2S meter) it should be the 95.0%~105.0% of labelled amount；As a result should all meet
Regulation.
11, it packs
A: aluminum-plastic packaged
After the PVC got and aluminium foil cleaning, it is sent into packer's bay；
Host general supply is opened, and sets temperature, forms 100 DEG C -130 DEG C of heating temperature, heat-sealing temperature 140-170
℃.Aluminium-coating Packer is preheated into 20min, it is first-class after the forming temperature of equipment, heat-sealing temperature, cooling water supply situation are normal
Aluminium foil and PVC, test-run a machine.After test-run a machine is normal, it can add medicine to and start to produce, and strictly press " aluminum-plastic-aluminum Autoblisterpackagingmachine mark
Quasi- operating instruction " operation.
Each meter parameter is checked within every 30-40 minutes during aluminum-plastic packaged, as a result charges to the record of production；
In process of production, following check is carried out to semi-finished product: notices that cutting position is correct, pressing is tight, dotted line
Closely sealed line is clear.Lot number, validity period should be clear, correct；Medicine plate answers foreign in appearance, and medicine plate seals situation without wrinkling:
Capsule surroundings answer hot wind tight, and reticulate pattern is clear；Bubble-cap quality: bubble-cap is answered well-pressed；Explosive payload: explosive payload is answered correctly, without vacuole
After the drug inspection statement of compliance for being connected to Quality Mgmt Dept, workshop can handle storage formality.
Production scale can be amplified 30,000 by the present invention, and it is slow as a result to meet R-lansoprazole by the inspection of its indices
Release the relevant regulations under application for registration standard and Chinese Pharmacopoeia two annex capsule items of version in 2010 of capsule.
Embodiment 1
A kind of preparation method of the capsule pharmaceutical containing R-lansoprazole sustained release preparation is completed using above-mentioned preparation method,
The mass ratio of each raw material is as follows:
R-lansoprazole in base ball raw material: sodium carboxymethylcellulose: sucrose: dextrin: starch: natrium carbonicum calcinatum=150:
50:200:100:50；
Hydroxypropyl methylcellulose in isolating layer material: talcum powder: titanium dioxide=50:15:10；
Methacrylic resin copolymer L100 in coatings A raw material: Macrogol 6000: Tween 80: lemon triethylenetetraminehexaacetic acid
Ester: titanium dioxide: talcum powder=50:2:10:30:4:15；
Eudragit S 100 in coatings B raw material: Macrogol 6000: Tween 80: triethyl citrate: titanium white
Powder: talcum powder=150:6:30:100:12:60；
It prepares in coating micro-pill A, used R-lansoprazole, hydroxypropyl methylcellulose and methacrylic resin copolymer
The mass ratio of L100 is R-lansoprazole: hydroxypropyl methylcellulose: methacrylic resin copolymer L100=150:50:50；
It prepares in coating micro-pill B, the matter of used R-lansoprazole, hydroxypropyl methylcellulose and Eudragit S 100
Amount is than being R-lansoprazole: hydroxypropyl methylcellulose: Eudragit S 100=150:50:150；
The quantity ratio of prepared coating micro-pill A and coating micro-pill B are 1:1.
The present embodiment respectively walks prepared product can reach requirement in the above method respectively.
Embodiment 2
A kind of preparation method of the capsule pharmaceutical containing R-lansoprazole sustained release preparation is completed using above-mentioned preparation method,
The mass ratio of each raw material is as follows:
R-lansoprazole in base ball raw material: sodium carboxymethylcellulose: sucrose: dextrin: starch: natrium carbonicum calcinatum=450:
150:600:200:100；
Hydroxypropyl methylcellulose in isolating layer material: talcum powder: titanium dioxide=100:45:20；
Methacrylic resin copolymer L100 in coatings A raw material: Macrogol 6000: Tween 80: lemon triethylenetetraminehexaacetic acid
Ester: titanium dioxide: talcum powder=100:6:20:70:12:45；
Eudragit S 100 in coatings B raw material: Macrogol 6000: Tween 80: triethyl citrate: titanium white
Powder: talcum powder=300:18:60:200:36:120；
It prepares in coating micro-pill A, used R-lansoprazole, hydroxypropyl methylcellulose and methacrylic resin copolymer
The mass ratio of L100 is R-lansoprazole: hydroxypropyl methylcellulose: methacrylic resin copolymer L100=450:100:100；
It prepares in coating micro-pill B, the matter of used R-lansoprazole, hydroxypropyl methylcellulose and Eudragit S 100
Amount is than being R-lansoprazole: hydroxypropyl methylcellulose: Eudragit S 100=450:100:300；
The quantity ratio of prepared coating micro-pill A and coating micro-pill B are 1:5.
The present embodiment respectively walks prepared product can reach requirement in the above method respectively.
Embodiment 3
A kind of preparation method of the capsule pharmaceutical containing R-lansoprazole sustained release preparation is completed using above-mentioned preparation method,
The mass ratio of each raw material is as follows:
R-lansoprazole in base ball raw material: sodium carboxymethylcellulose: sucrose: dextrin: starch: natrium carbonicum calcinatum=200:
80:300:120:70；
Hydroxypropyl methylcellulose in isolating layer material: talcum powder: titanium dioxide=70:20:12；
Methacrylic resin copolymer L100 in coatings A raw material: Macrogol 6000: Tween 80: lemon triethylenetetraminehexaacetic acid
Ester: titanium dioxide: talcum powder=70:3:12:40:6:20；
Eudragit S 100 in coatings B raw material: Macrogol 6000: Tween 80: triethyl citrate: titanium white
Powder: talcum powder=200:9:40:120:18:80；
It prepares in coating micro-pill A, used R-lansoprazole, hydroxypropyl methylcellulose and methacrylic resin copolymer
The mass ratio of L100 is R-lansoprazole: hydroxypropyl methylcellulose: methacrylic resin copolymer L100=200:70:70；
It prepares in coating micro-pill B, the matter of used R-lansoprazole, hydroxypropyl methylcellulose and Eudragit S 100
Amount is than being R-lansoprazole: hydroxypropyl methylcellulose: Eudragit S 100=200:70:200；
The quantity ratio of prepared coating micro-pill A and coating micro-pill B are 1:2.
The present embodiment respectively walks prepared product can reach requirement in the above method respectively.
Embodiment 4
A kind of preparation method of the capsule pharmaceutical containing R-lansoprazole sustained release preparation is completed using above-mentioned preparation method,
The mass ratio of each raw material is as follows:
R-lansoprazole in base ball raw material: sodium carboxymethylcellulose: sucrose: dextrin: starch: natrium carbonicum calcinatum=400:
120:500:180:90；
Hydroxypropyl methylcellulose in isolating layer material: talcum powder: titanium dioxide=90:40:18；
Methacrylic resin copolymer L100 in coatings A raw material: Macrogol 6000: Tween 80: lemon triethylenetetraminehexaacetic acid
Ester: titanium dioxide: talcum powder=80:5:18:60:10:40；
Eudragit S 100 in coatings B raw material: Macrogol 6000: Tween 80: triethyl citrate: titanium white
Powder: talcum powder=250:15:50:180:30:100；
It prepares in coating micro-pill A, used R-lansoprazole, hydroxypropyl methylcellulose and methacrylic resin copolymer
The mass ratio of L100 is R-lansoprazole: hydroxypropyl methylcellulose: methacrylic resin copolymer L100=400:90:80；
It prepares in coating micro-pill B, the matter of used R-lansoprazole, hydroxypropyl methylcellulose and Eudragit S 100
Amount is than being R-lansoprazole: hydroxypropyl methylcellulose: Eudragit S 100=400:90:250；
The quantity ratio of prepared coating micro-pill A and coating micro-pill B are 1:4.
The present embodiment respectively walks prepared product can reach requirement in the above method respectively.
Embodiment 5
A kind of preparation method of the capsule pharmaceutical containing R-lansoprazole sustained release preparation is completed using above-mentioned preparation method,
The mass ratio of each raw material is as follows:
R-lansoprazole in base ball raw material: sodium carboxymethylcellulose: sucrose: dextrin: starch: natrium carbonicum calcinatum=300:
100:420:155:85；
Hydroxypropyl methylcellulose in isolating layer material: talcum powder: titanium dioxide=80:30:15；
Methacrylic resin copolymer L100 in coatings A raw material: Macrogol 6000: Tween 80: lemon triethylenetetraminehexaacetic acid
Ester: titanium dioxide: talcum powder=75:4:15:50:8:30；
Eudragit S 100 in coatings B raw material: Macrogol 6000: Tween 80: triethyl citrate: titanium white
Powder: talcum powder=225:12:45:150:24:90；
It prepares in coating micro-pill A, used R-lansoprazole, hydroxypropyl methylcellulose and methacrylic resin copolymer
The mass ratio of L100 is R-lansoprazole: hydroxypropyl methylcellulose: methacrylic resin copolymer L100=300:80:75；
It prepares in coating micro-pill B, the matter of used R-lansoprazole, hydroxypropyl methylcellulose and Eudragit S 100
Amount is than being R-lansoprazole: hydroxypropyl methylcellulose: Eudragit S 100=300:80:225；
The quantity ratio of prepared coating micro-pill A and coating micro-pill B are 1:3.
The present embodiment respectively walks prepared product can reach requirement in the above method respectively.
To 5 capsule pharmaceutical of the gained containing R-lansoprazole sustained release preparation of the embodiment of the present invention and raw material according to U.S. FDA
The drug release determination method of announcement carries out the following studies respectively:
By capsule pharmaceutical of the gained containing R-lansoprazole sustained release preparation of the embodiment of the present invention 5 500mL 0.1N dilute salt
After impregnating two hours in acid solution, its release under different dissolution mediums is tested, as a result as follows:
Capsule pharmaceutical of the gained of 1 embodiment of the present invention of table 5 containing R-lansoprazole sustained release preparation in acid after two hours
Dissolution test result in pH7.0 buffer release medium
Capsule pharmaceutical of the gained of 2 embodiment of the present invention of table 5 containing R-lansoprazole sustained release preparation in acid after two hours
Dissolution test result in pH6.8 buffer release medium
Capsule pharmaceutical of the gained of 3 embodiment of the present invention of table 5 containing R-lansoprazole sustained release preparation in acid after two hours
Dissolution test result in pH4.5 buffer release medium
Capsule pharmaceutical of the gained of 4 embodiment of the present invention of table 5 containing R-lansoprazole sustained release preparation in acid after two hours
Dissolution test result in water
From the above results, the present invention contains the capsule pharmaceutical of R-lansoprazole sustained release preparation in different dissolution mediums
Release behavior it is obviously dissimilar, that is to say, that the present invention contain the capsule pharmaceutical of R-lansoprazole sustained release preparation for pH value dependence
Property preparation, release behavior are influenced by gastrointestinal tract acid or alkali environment, with dissolution medium pH value increase rate of release also with
Accelerate.
Coating micro-pill A used by the embodiment of the present invention 5 and coating micro-pill B is molten in the dilute hydrochloric acid of 500mL 0.1N respectively
After impregnating two hours in liquid, its release under different dissolution mediums is tested, as a result as follows:
Release of 5 embodiment of the present invention of table, the 5 coating micro-pill A in acid after 2 hours in pH7.0 buffer release medium
Degree test result (be equivalent to mark content 1/4)
Release of 6 embodiment of the present invention of table, the 5 coating micro-pill A in acid after 2 hours in pH6.8 buffer release medium
Degree test result (be equivalent to mark content 1/4)
Dissolution test result of 7 embodiment of the present invention of table, the 5 coating micro-pill A in acid after 2 hours in water (is equivalent to
Indicate the 1/4 of content)
Release of 8 embodiment of the present invention of table, the 5 coating micro-pill A in acid after 2 hours in pH4.5 buffer release medium
Degree test result (be equivalent to mark content 1/4)
Release of 9 embodiment of the present invention of table, the 5 coating micro-pill B in acid after 2 hours in pH7.0 buffer release medium
Degree test result (be equivalent to mark content 3/4)
Release of 10 embodiment of the present invention of table, the 5 coating micro-pill B in acid after 2 hours in pH6.8 buffer release medium
Degree test result (be equivalent to mark content 3/4)
Release of 11 embodiment of the present invention of table, the 5 coating micro-pill B in acid after 2 hours in pH4.5 buffer release medium
Degree test result (be equivalent to mark content 3/4)
Dissolution test result of 12 embodiment of the present invention of table, the 5 coating micro-pill B in acid after 2 hours in water (is equivalent to
Indicate the 3/4 of content)
Without the release of peracid treatment, test result is as follows:
13 embodiment of the present invention of table, 5 capsule pharmaceutical of the gained containing R-lansoprazole sustained release preparation is direct without acid solution
Dissolution test result in pH70 buffer release medium
14 embodiment of the present invention of table, 5 capsule pharmaceutical of the gained containing R-lansoprazole sustained release preparation is direct without acid solution
Dissolution test result in pH6.8 buffer release medium
15 embodiment of the present invention of table, 5 capsule pharmaceutical of the gained containing R-lansoprazole sustained release preparation is direct without acid solution
Dissolution test result in pH4.5 buffer release medium
16 embodiment of the present invention of table, 5 capsule pharmaceutical of the gained containing R-lansoprazole sustained release preparation is direct without acid solution
Dissolution test result in water
By the above results: the capsule pharmaceutical that the present invention contains R-lansoprazole sustained release preparation is by 2 kinds of difference pH
The pellet of dependence forms, wherein coating micro-pill A after acid solution is handled 2 hours other solution can in 30 minutes it is basic
On can discharge completely, coating micro-pill B only at phosphate-buffered night (pH6.8, pH7.0) 120 minutes be initially slow release, and
It discharged and accelerates at 150 minutes or so, substantially completely discharged in 4 hours, this product is more sensitive to the pH of dissolution medium, with molten
The increase rate of release of PH values is also with increase out.
The characteristic of product according to the present invention mixes R-lansoprazole and suitable auxiliary material drug containing piller is made,
After drying, packet separation layer, then the controlled release layer of 2 different release characteristics is wrapped respectively, finally mix according to a certain percentage, thus
Achieve the purpose that biphasic controlled release is sustained.
Compatibility test is carried out to the auxiliary material that the present invention selects, main ingredient and auxiliary material are mixed in a certain ratio (mass ratio),
Take it is a certain amount of, by factors affecting stability test method, respectively in strong light (4500 ± 500Lux), high temperature (60 DEG C), high humidity (phase
To humidity 90 ± 5%) under conditions of place 10 days, check that content and optical purity place front and back and have unchanged, while observing outer
The variation of the drugs character such as sight, color, while parallel control experiment is done respectively with bulk pharmaceutical chemicals and auxiliary material, it is bulk pharmaceutical chemicals sheet to differentiate
The variation of body or the influence of auxiliary material, as a result as follows:
The supplementary material compatibility test result of the present invention of table 17
By above-mentioned compatibility test result it is found that R-lansoprazole and auxiliary material used are after certain proportion mixes, through 10
Its Qiang Guang (4500 ± 500Lux), high temperature (60 DEG C), high humidity (relative humidity 90 ± 5%) condition test, as the result is shown at 60 DEG C
After heating 10 days, the color of each mixed powder becomes off-white color from white, and color is deepened, other each condition lower right Lan Suola
The content (calculating by dry product) of azoles compares basic no variation with raw material, and (analysis reason may be evaluated error or auxiliary material each
Under the conditions of have protective effect to raw material), loss on drying has the weight gain of several auxiliary materials obvious, this suggest that if using it is necessary to
Pay attention to the moisture-proof of Key works Drug packing.
Stability study shows: the capsule pharmaceutical that the present invention contains R-lansoprazole sustained release preparation is tested through influence factor
(high temperature, high humidity, strong illumination) 10 days, the capsule pharmaceutical of the invention containing R-lansoprazole sustained release preparation is in height as the result is shown
Under the conditions of temperature, strong illumination, related substance is increased slightly, and content is declined slightly, and other test results nothing compared with 0 day obviously changes
Become, therefore this product answers shading, sealing, saves at shady and cool drying.6 months quality of accelerated test are stablized, and keep sample 24 lunar geology for a long time
Amount is stablized.
According to the present invention the capsule pharmaceutical accelerated test containing R-lansoprazole sustained release preparation and long term test as a result, saying
Bright capsule pharmaceutical of the present invention containing R-lansoprazole sustained release preparation is in shading, sealing, under the conditions of at shady and cool drying preservation compared with
Stablize, validity period can reach 2 years or more.
Drug inspection, phase are carried out to the capsule pharmaceutical obtained by 1-5 of the embodiment of the present invention containing R-lansoprazole sustained release preparation
Relevant criterion and requirement of the method referring to " Chinese Pharmacopoeia " version in 2010 of drug inspection are closed, gained inspection result is as follows:
18 embodiment of the present invention of table, 1 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation
Conclusion: 1 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation of the embodiment of the present invention meets phase
Close regulation.
19 embodiment of the present invention of table, 2 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation
Conclusion: 2 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation of the embodiment of the present invention meets phase
Close regulation.
20 embodiment of the present invention of table, 3 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation
Conclusion: 3 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation of the embodiment of the present invention meets phase
Close regulation.
21 embodiment of the present invention of table, 4 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation
Conclusion: 4 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation of the embodiment of the present invention meets phase
Close regulation.
22 embodiment of the present invention of table, 5 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation
Conclusion: 5 capsule pharmaceutical inspection result of the gained containing R-lansoprazole sustained release preparation of the embodiment of the present invention meets phase
Close regulation.
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that the above various embodiments is only used
To illustrate technical solution of the present invention, rather than its limitations；Those skilled in the art should understand that: without departing substantially from this hair
It in the case where bright spirit and scope, is possible to modify the technical solutions described in the foregoing embodiments, or to wherein
Some or all of technical characteristic is equivalently replaced；And these are modified or replaceed, and do not make the essence of corresponding technical solution
It departs from the scope of the technical solutions of the embodiments of the present invention；It is, therefore, intended that in the following claims including belonging to the present invention
All these substitutions and modifications in range.
Claims (7)
1. a kind of R-lansoprazole sustained release preparation, which is characterized in that the R-lansoprazole sustained release preparation includes base ball, the base
Separation layer and coatings are successively coated on the outside of ball；
The raw material of the base ball is R-lansoprazole: sodium carboxymethylcellulose: sucrose: dextrin: starch: natrium carbonicum calcinatum=300:
100:420:155:85；
The raw material of the separation layer is hydroxypropyl methylcellulose: talcum powder: titanium dioxide=80:30:15；
The coatings include including coatings A and coatings B；
The raw material of the coatings A is methacrylic resin copolymer L100: Macrogol 6000: Tween 80: citric acid three
Ethyl ester: titanium dioxide: talcum powder=75:4:15:50:8:30；
The raw material of the coatings B is Eudragit S 100: Macrogol 6000: Tween 80: triethyl citrate: titanium white
Powder: talcum powder=225:12:45:150:24:90；
The base ball for coating the coatings A is mixed with the base ball for coating the coatings B with the quantity ratio of 1:3.
2. a kind of preparation method of R-lansoprazole sustained release preparation as described in claim 1, which is characterized in that by base ball raw material
It is granulated after mixing, coats separation layer on gained base ball surface, coat coating in the insulation surface for the base ball for being coated with separation layer
Layer, obtains a kind of R-lansoprazole sustained release preparation.
3. a kind of preparation method of R-lansoprazole sustained release preparation according to claim 2, which is characterized in that the granulation
It is granulated in the process using water or syrup；
The syrup is aqueous sucrose solution；
The mass fraction of the aqueous sucrose solution is 25%.
4. a kind of preparation method of R-lansoprazole sustained release preparation according to claim 2, which is characterized in that the cladding
Solvent is used during separation layer；
The solvent includes one or both of second alcohol and water.
5. a kind of preparation method of R-lansoprazole sustained release preparation according to claim 2, which is characterized in that the cladding
Solvent is used during coatings；
The solvent includes one or both of second alcohol and water.
6. including a kind of drug of R-lansoprazole sustained release preparation described in claim 1.
7. drug according to claim 6, which is characterized in that the drug includes capsule pharmaceutical.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102600109A (en) * | 2012-04-13 | 2012-07-25 | 河南新帅克制药股份有限公司 | Dexlansoprazole sustained release capsule and preparation method thereof |
| CN103565770A (en) * | 2012-07-31 | 2014-02-12 | 北京阜康仁生物制药科技有限公司 | Dexlansoprazole enteric-coated slow controlled-release pellet tablets |
| CN104523654A (en) * | 2014-12-15 | 2015-04-22 | 北京红太阳药业有限公司 | Dexlansoprazole sustained-release capsule and preparation method thereof |
| CN105769824A (en) * | 2014-12-16 | 2016-07-20 | 四川海思科制药有限公司 | Dexlansoprazole slow-release capsule and preparation method thereof |
-
2017
- 2017-03-28 CN CN201710190699.6A patent/CN106822045B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102600109A (en) * | 2012-04-13 | 2012-07-25 | 河南新帅克制药股份有限公司 | Dexlansoprazole sustained release capsule and preparation method thereof |
| CN103565770A (en) * | 2012-07-31 | 2014-02-12 | 北京阜康仁生物制药科技有限公司 | Dexlansoprazole enteric-coated slow controlled-release pellet tablets |
| CN104523654A (en) * | 2014-12-15 | 2015-04-22 | 北京红太阳药业有限公司 | Dexlansoprazole sustained-release capsule and preparation method thereof |
| CN105769824A (en) * | 2014-12-16 | 2016-07-20 | 四川海思科制药有限公司 | Dexlansoprazole slow-release capsule and preparation method thereof |
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| CN106822045A (en) | 2017-06-13 |
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Inventor after: Li Chunli Inventor after: Yu Liqiang Inventor after: Hu Chunzhen Inventor after: Lu Zhihong Inventor after: Sun Jiliang Inventor before: Li Chunli Inventor before: Yu Liqiang Inventor before: Hu Chunzhen Inventor before: Lu Zhihong Inventor before: Sun Ji |