CN108434117A - A kind of preparation method of omeprazole enteric-coated capsules - Google Patents
A kind of preparation method of omeprazole enteric-coated capsules Download PDFInfo
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- CN108434117A CN108434117A CN201810268484.6A CN201810268484A CN108434117A CN 108434117 A CN108434117 A CN 108434117A CN 201810268484 A CN201810268484 A CN 201810268484A CN 108434117 A CN108434117 A CN 108434117A
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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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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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
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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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
- A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
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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
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Abstract
The invention discloses a kind of preparation methods of omeprazole enteric-coated capsules, it is characterised in that：Include the following steps：S1 blank capsule cores are coated；S1 1 is configured to containing 2~8% hydroxypropylcellulose aqueous solutions；Hydroxypropylcellulose aqueous solution is coated to blank sugar-pill by S1 2 by blank sugar-pill, obtains coating capsule core；S2 carries out carrying pack clothing to coating capsule core, obtains carrying pill；S3 carries out isolation coat to carrying pill, obtains isolation ball；S4 1 33% Tween 80 aqueous solution, triethyl citrate and glycerin monostearate is added in the purified water that temperature is 70~80 DEG C, obtains the first suspension；First suspension is added into 55 dispersion liquids of Utech L30D S4 2, obtains the first enteric liquid；Ball will be isolated in S4 3, and the first enteric liquid is sprayed on isolation ball, the first enteric coated pill is obtained；S5 1 takes triethyl citrate, Utech L30D 55, purified water, obtains the second enteric liquid；Second enteric liquid is sprayed on the first enteric coated pill by S5 2, obtains the second enteric coated pill；S6 pairs of the second enteric coated pill is dusted, polishes, packs.
Description
Technical field
The present invention relates to the technical fields of pharmaceutical preparation, refer to a kind of preparation of omeprazole enteric-coated capsules specifically
Method.
Background technology
Omeprazole is proton pump inhibitor class anti-ulcer agent, can treat duodenal ulcer, gastric ulcer and esophagitis, and
The effect of intractable peptic ulcer and serious esophageal reflux ulcer can be eliminated, is splendid, and side effect is rarely found.
Omeprazole is unstable, is easy to degrade in acid and neutral medium, his stability also by light, humidity,
The influence of heat, organic solvent, because of the degradation of Omeprazole, can also find preparation even if under normally storage use condition
Discoloration, while Omeprazole poor solubility there is a problem of working slow.
To solve the above-mentioned problems, it is therefore necessary to which it is simple to design preparation process, and it is convenient to prepare, and effectively solves Aomei and draw
A kind of preparation method of azoles degradable omeprazole enteric-coated capsules in acid and neutral medium.
Invention content
The present invention provides a kind of sand paper changer, is existed in the prior art for solving：Omeprazole is unstable, especially
It is easy to explain in acid and neutral medium, its stability is also influenced by light, humidity, heat, organic solvent etc., Yin Ao
The problem of azoles self-characteristic, is drawn by U.S., larger to make the medical value performance of Omeprazole there is technical issues that.
In order to solve the above-mentioned technical problem, reach and using Omeprazole drug, the medicinal maximum of Omeprazole can be played
The advantageous effect of value.
The invention is realized by the following technical scheme：Include the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to containing 2~8% hydroxypropylcelluloses
Aqueous solution；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill obtains coating capsule core；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 70~80 that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
DEG C purified water in, high-speed uniform shear 10min, obtain the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill；
S5：Second of enteric coating is carried out to isolation ball；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, the second enteric liquid is obtained；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill；
S6：Second enteric coated pill is dusted, polish, is packed.
The present invention is the preparation method of omeprazole enteric-coated capsules, and existing omeprazole enteric-coated capsules play a role in vivo
When cannot always play maximum medical value, such as Omeprazole drug is always discharged or is discharged too late in advance.
Find that the preparation process of existing capsulae enterosolubilis is complicated, and cannot effectively play by long-term experimental study
Maximum medical value, therefore capsulae enterosolubilis of the present invention is set.
The present invention is first coated blank capsule core, and blank capsule core is sugar-pill, is mainly prepared by sugarcane sugar and starch,
And containing sugared hydroxyl, the effect of isolation is primarily served after blank capsule core coating, can blocked sugar hydroxyl, in this way will be to the steady of drug
It is qualitative play the role of it is great.
In omeprazole enteric-coated capsules preparation process, in order to allow medicament to play maximum medical value, therefore it is right
Enteric coating refines, at twice enteric coating, and the main component of the first enteric coating is Utech L30D-55, citric acid
The main component of triethyl, glycerin monostearate, 33% Tween-80 aqueous solution, purified water, the second enteric coating is Utech
L30D-55, triethyl citrate, purified water；Ingredient twice is different, different in the effect that different phase plays.
It is preferred that blank capsule core coating weight gain is 3%.It is obtained by long-term experiment, increases weight when being 3%, be conducive to the temperature of drug
Degree；By enteric coating twice, quick release when to enable capsule to reach enteron aisle, the above-mentioned each step collaboration of the present invention is made
With the stability and drug later stage release function of maximum drug early period can be reached, to make Omeprazole play maximum medicine
With value, reach the optimum efficiency for the treatment of.
In order to preferably realize the present invention, further, the S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete
Full swelling, is configured to containing 5% hydroxypropylcellulose aqueous solution.
In order to preferably realize the present invention, further, step S3 is as follows：
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
Cellulose/hydroxypropyl methylcellulose aqueous solution；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, and then obtain isolation ball.
In order to preferably realize the present invention, further, the hydroxypropylcellulose prepared in the step S3-1/hydroxypropyl first is fine
The plain aqueous solution of dimension, wherein the Solute mass ratio of hydroxypropylcellulose and hydroxypropyl methylcellulose are 1:1~10.
In order to preferably realize the present invention, further, the hydroxypropylcellulose prepared in the step S3-1/hydroxypropyl first is fine
The plain aqueous solution of dimension, wherein the Solute mass ratio of hydroxypropylcellulose and hydroxypropyl methylcellulose are 1:9.
In order to preferably realize the present invention, further, isolation coat in the step S3, separation layer weightening 12~
18%.
In order to preferably realize the present invention, further, isolation coat in the step S3, separation layer weightening 15%.
The Solute mass of hydroxypropylcellulose and hydroxypropyl methylcellulose ratio is 1:1~10, it can enable separation layer in this stage
It is enough to be discharged in point range, but in order to achieve the effect that best fixed point release, therefore preferably hydroxypropylcellulose and hydroxyl
The Solute mass ratio of third methylcellulose is 1:9, hydroxypropylcellulose get over multiform at film it is finer and close, to fixed point when not fully release
It puts, is obtained by long-term experiment, as hydroxypropylcellulose dosage is reduced, 30min or so, which can discharge, reaches 95% or more, from
And quick release is allowed medicament to, medical value is most played soon.
In order to preferably realize the present invention, further, step S2 is as follows：
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 5~15% hydroxypropyls
Ylmethyl cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 5~15% hydroxypropyl methyl cellulose aqueous solutions, and purified water is added, is led to
It is stirred well to the second suspension after crossing high speed shear 10min；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, obtain carrying pill.
In order to preferably realize the present invention, further, S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred
To complete swelling, it is configured to contain 10% hydroxypropyl methyl cellulose aqueous solution.
In order to preferably realize the present invention, further, the first time enteric coating, the first enteric layer weightening 30~
35%；Second of enteric coating, the second enteric layer weightening 10~15%.
Compared with prior art, the present invention haing the following advantages and advantageous effect：The present invention is coated by blank capsule core, is had
Conducive to the temperature of drug；By enteric coating twice, quick release when to enable capsule to reach enteron aisle, each step of the present invention
Rapid synergistic effect, can reach the stability and drug later stage release function of maximum drug early period, to make Omeprazole play
Maximum medical value reaches the optimum efficiency for the treatment of.
Specific implementation mode
The present invention is described in further detail with reference to embodiment, embodiments of the present invention are not limited thereto.
Embodiment 1：
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 2% hydroxypropylcellulose
Liquid crosses 80 mesh screens；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill, 35~40 DEG C of control material temperature, spray process maintain coating solution 50~100rpm of mixing speed, dry after coating
To moisture≤1.5%, coating capsule core is obtained；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 5% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 5% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 1:1；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 12%；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 70 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 30% after having sprayed；
S5：Second of enteric coating；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, 80 mesh screens is crossed, obtains
Second enteric liquid；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill, 30~33 DEG C of control material temperature degree,
Spray process maintains suspension 80~120rpm of mixing speed, and dry to moisture≤4.5% after having sprayed, second enteric layer increases
Weigh 10%；
S6：Second enteric coated pill is dusted, polish, is packed.
Embodiment 2：
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 8% hydroxypropylcellulose
Liquid crosses 80 mesh screens；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill, 35~40 DEG C of control material temperature, spray process maintain coating solution 50~100rpm of mixing speed, dry after coating
To moisture≤1.5%, coating capsule core is obtained；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 15% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 15% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 10；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 18%；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 80 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 35% after having sprayed；
S5：Second of enteric coating；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, 80 mesh screens is crossed, obtains
Second enteric liquid；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill, 30~33 DEG C of control material temperature degree,
Spray process maintains suspension 80~120rpm of mixing speed, and dry to moisture≤4.5% after having sprayed, second enteric layer increases
Weigh 15%；
S6：Second enteric coated pill is dusted, polish, is packed.
Embodiment 3：
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 4% hydroxypropylcellulose
Liquid crosses 80 mesh screens；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill, 35~40 DEG C of control material temperature, spray process maintain coating solution 50~100rpm of mixing speed, dry after coating
To moisture≤1.5%, coating capsule core is obtained；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 7% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 7% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 1:2；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 14%；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 72 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 32% after having sprayed；
S5：Second of enteric coating；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, 80 mesh screens is crossed, obtains
Second enteric liquid；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill, 30~33 DEG C of control material temperature degree,
Spray process maintains suspension 80~120rpm of mixing speed, and dry to moisture≤4.5% after having sprayed, second enteric layer increases
Weigh 12%；
S6：Second enteric coated pill is dusted, polish, is packed.
Embodiment 4：
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 5% hydroxypropylcellulose
Liquid crosses 80 mesh screens；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill, 35~40 DEG C of control material temperature, spray process maintain coating solution 50~100rpm of mixing speed, dry after coating
To moisture≤1.5%, coating capsule core is obtained；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 8% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 8% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 1:5；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 15%；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 74 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 33% after having sprayed；
S5：Second of enteric coating；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, 80 mesh screens is crossed, obtains
Second enteric liquid；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill, 30~33 DEG C of control material temperature degree,
Spray process maintains suspension 80~120rpm of mixing speed, and dry to moisture≤4.5% after having sprayed, second enteric layer increases
Weigh 13%；
S6：Second enteric coated pill is dusted, polish, is packed.
Embodiment 5：
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 6% hydroxypropylcellulose
Liquid crosses 80 mesh screens；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill, 35~40 DEG C of control material temperature, spray process maintain coating solution 50~100rpm of mixing speed, dry after coating
To moisture≤1.5%, coating capsule core is obtained；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 10% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 10% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 1:9；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 15%；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 75 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 33% after having sprayed；
S5：Second of enteric coating；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, 80 mesh screens is crossed, obtains
Second enteric liquid；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill, 30~33 DEG C of control material temperature degree,
Spray process maintains suspension 80~120rpm of mixing speed, and dry to moisture≤4.5% after having sprayed, second enteric layer increases
Weigh 13%；
S6：Second enteric coated pill is dusted, polish, is packed.
Embodiment 6：
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 6% hydroxypropylcellulose
Liquid crosses 80 mesh screens；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill, 35~40 DEG C of control material temperature, spray process maintain coating solution 50~100rpm of mixing speed, dry after coating
To moisture≤1.5%, coating capsule core is obtained；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 12% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 12% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 1:9；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 16%；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 76 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 34% after having sprayed；
S5：Second of enteric coating；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, 80 mesh screens is crossed, obtains
Second enteric liquid；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill, 30~33 DEG C of control material temperature degree,
Spray process maintains suspension 80~120rpm of mixing speed, and dry to moisture≤4.5% after having sprayed, second enteric layer increases
Weigh 14%；
S6：Second enteric coated pill is dusted, polish, is packed.
Comparative example 1
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is carried out to carry pack clothing, obtains carrying pill；
S1-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 1% hydroxypropyl first
Base cellulose aqueous solution；
S1-2：Magnesium omeprazole is soaked with containing 1% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S1-3：The obtained blank capsule cores of step S1-2 are placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to blank capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S2：Isolation coat is carried out to carrying pill, obtains isolation ball；
S2-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 1:1；
S2-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S2-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 10%；
S3：First time enteric coating is carried out to isolation ball；
S3-1：It is 60 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S3-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S3-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 25% after having sprayed；
S4：Second of enteric coating；
S4-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, 80 mesh screens is crossed, obtains
Second enteric liquid；
S4-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill, 30~33 DEG C of control material temperature degree,
Spray process maintains suspension 80~120rpm of mixing speed, and dry to moisture≤4.5% after having sprayed, second enteric layer increases
Weigh 5%；
S6：Second enteric coated pill is dusted, polish, is packed.
Comparative example 2
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 3% hydroxypropylcellulose
Liquid crosses 80 mesh screens；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill, 35~40 DEG C of control material temperature, spray process maintain coating solution 50~100rpm of mixing speed, dry after coating
To moisture≤1.5%, coating capsule core is obtained；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 10% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 10% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 4:1；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 19%；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 89 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 50% after having sprayed；
S5：Second of enteric coating；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, 80 mesh screens is crossed, obtains
Second enteric liquid；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained
It is sprayed on the first enteric coated pill, to form the second enteric layer, and then obtains the second enteric coated pill, 30~33 DEG C of control material temperature degree,
Spray process maintains suspension 80~120rpm of mixing speed, and dry to moisture≤4.5% after having sprayed, second enteric layer increases
Weigh 1%；
S6：Second enteric coated pill is dusted, polish, is packed.
Comparative example 3
A kind of preparation method of omeprazole enteric-coated capsules, includes the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 5% hydroxypropylcellulose
Liquid crosses 80 mesh screens；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank
Sugar-pill, 35~40 DEG C of control material temperature, spray process maintain coating solution 50~100rpm of mixing speed, dry after coating
To moisture≤1.5%, coating capsule core is obtained；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 10% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 10% hydroxypropyl methyl cellulose aqueous solution, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min, crosses 80 mesh screens；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained sprays
On mist to coating capsule core, 32~35 DEG C of control material temperature, spray process maintains suspension 80~120rpm of mixing speed, has sprayed
It dries afterwards to moisture≤4.5%, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl
The Solute mass ratio of cellulose/hydroxypropyl methylcellulose aqueous solution, the hydroxypropylcellulose and hydroxypropyl methylcellulose is 1:9；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed
Stirring obtains insulating liquid to uniformly mixed after shearing homogenizes 10min, crosses 80 mesh screens；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, by insulating liquid be sprayed to carry pill on, to formed every
Absciss layer, 32~35 DEG C of control material temperature, spray process maintain suspension 80~120rpm of mixing speed, dry to water after having sprayed
Divide≤4.5%, and then obtains isolation ball, the separation layer weightening 15%；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 75 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, a small amount of purified water is added is stirred continuously and be cooled to room temperature, and obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously
To being uniformly mixed, the first enteric liquid is obtained, crosses 80 mesh screens；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, to be sprayed to
It is isolated on ball, to form the first enteric layer, and then obtains the first enteric coated pill, 30~33 DEG C of control material temperature, spray process
Suspension 80~120rpm of mixing speed is maintained, it is dry to moisture≤4.5%, the first enteric layer weightening 50% after having sprayed；
S6：Second enteric coated pill is dusted, polish, is packed.
Experimental result compares:
The present embodiment 1~6 meets enteric coated preparations quality standard described in Chinese Pharmacopoeia, passes through Examples 1 to 6 and comparative example 1
Comparison learns that comparative example 1 is not coated blank capsule core, while being done to the sugar-pill after coating to Examples 1 to 6 and comparative example
It when the test of friability, is as a result apparent from, the friability for doing blank capsule core coating is significantly better than uncoated blank capsule core.
And in finally obtained product, main ingredient in comparative example 1 easily with sugared hydroxyl reaction, to seriously affect the stability of main ingredient,
And the release process for seriously affecting the drug later stage, seriously hinders the performance of drug value.
It is learnt by Examples 1 to 6 and the comparison of comparative example 2, the hydroxypropylcellulose of separation layer and hydroxypropyl first are fine in comparative example 2
The Solute mass ratio of dimension element is 4:1, it is found by detecting, finally formed isolation tunic is especially close, is very unlikely to discharge,
When fixed point release, release is slow, and release time is long, has influenced the Best Times of drug release completely, to influence most
The time of good treatment.
It is learnt by Examples 1 to 6 and the comparison of comparative example 2, disposable enteric coating is used in comparative example 3, in comparative example 3
The position that enteric layer also fails to reach enteron aisle fixed point release begins to discharge, so that drug also premature release, so that
Drug discharges in advance, can also reach the time of optimal drug treatment.
Although an embodiment of the present invention has been shown and described, it will be understood by those skilled in the art that being：
These embodiments can be carried out a variety of change, modification, replacement and modification, the present invention by not departing under the principle of the present invention and objective
Range limited by claim and its equivalent.
Claims (10)
1. a kind of preparation method of omeprazole enteric-coated capsules, it is characterised in that：Include the following steps：
S1：Blank capsule core is coated；
S1-1：Hydroxypropylcellulose is dissolved in purified water to stir to complete swelling, is configured to water-soluble containing 2~8% hydroxypropylcelluloses
Liquid；
S1-2：By blank sugar-pill, it is placed in fluid bed, the hydroxypropylcellulose aqueous solution that step S1-1 is obtained is coated to blank sugar
Ball obtains coating capsule core；
S2：Coating capsule core is carried out carrying pack clothing, obtains carrying pill；
S3：Isolation coat is carried out to carrying pill, obtains isolation ball；
S4：First time enteric coating is carried out to isolation ball；
S4-1：It is 70~80 DEG C that temperature, which is added, in 33% Tween-80 aqueous solution, triethyl citrate and glycerin monostearate
In purified water, high-speed uniform shears 10min, obtains the first suspension；
S4-2：The first suspension that step S4-1 is obtained is added into Utech L30D-55 dispersion liquids, and is stirred continuously to mixed
It closes uniformly, obtains the first enteric liquid；
S4-3：The isolation ball that step S3 is obtained, is placed on fluid bed, and step S4-2, which is obtained the first enteric liquid, is sprayed to isolation
On ball, to form the first enteric layer, and then the first enteric coated pill is obtained；
S5：Second of enteric coating is carried out to isolation ball；
S5-1：Triethyl citrate, Utech L30D-55, purified water are taken, is uniformly mixed, the second enteric liquid is obtained；
S5-2：The first enteric coated pill that step S4-3 is obtained is placed in fluid bed, the second enteric liquid that step S5-1 is obtained is sprayed
To the first enteric coated pill, to form the second enteric layer, and then the second enteric coated pill is obtained；
S6：Second enteric coated pill is dusted, polish, is packed.
2. the preparation method of omeprazole enteric-coated capsules according to claim 1, it is characterised in that：The S1-1：By hydroxyl
The purified water that third cellulose is dissolved in is stirred to complete swelling, is configured to containing 5% hydroxypropylcellulose aqueous solution.
3. the preparation method of omeprazole enteric-coated capsules according to claim 1, it is characterised in that：The specific step of step S3
It is rapid as follows：
S3-1：By hydroxypropyl methylcellulose, hydroxypropylcellulose, add purified water, stirring is complete to being swollen, and is configured to 10% hydroxypropyl fiber
Element/hydroxypropyl methylcellulose aqueous solution；
S3-2：By magnesium stearate, talcum powder, 10% hydroxypropylcellulose/hydroxypropyl methylcellulose aqueous solution, purified water, high speed shear
Stirring obtains insulating liquid to uniformly mixed after homogenizing 10min；
S3-3：The load pill that step S2 is obtained is placed in fluid bed, insulating liquid is sprayed to and is carried on pill, to form isolation
Layer, and then obtain isolation ball.
4. the preparation method of omeprazole enteric-coated capsules according to claim 3, it is characterised in that：In the step S3-1
The hydroxypropylcellulose of preparation/hydroxypropyl methylcellulose aqueous solution, wherein the Solute mass ratio of hydroxypropylcellulose and hydroxypropyl methylcellulose
It is 1:1~10.
5. the preparation method of omeprazole enteric-coated capsules according to claim 4, it is characterised in that：In the step S3-1
The hydroxypropylcellulose of preparation/hydroxypropyl methylcellulose aqueous solution, wherein the Solute mass ratio of hydroxypropylcellulose and hydroxypropyl methylcellulose
It is 1:9.
6. according to the preparation method of claim 3~5 any one of them omeprazole enteric-coated capsules, it is characterised in that：It is described
Isolation coat in step S3, separation layer weightening 12~18%.
7. the preparation method of omeprazole enteric-coated capsules according to claim 6, it is characterised in that：The step S3 intervals
From coating, separation layer weightening 15%.
8. the preparation method of omeprazole enteric-coated capsules according to claim 1, it is characterised in that：Step S2 specific steps
It is as follows：
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to contain 5~15% hydroxypropyl first
Base cellulose aqueous solution；
S2-2：Magnesium omeprazole is soaked with containing 5~15% hydroxypropyl methyl cellulose aqueous solutions, and purified water is added, passes through height
It is stirred well to the second suspension after speed shearing 10min；
S2-3：The coating capsule core that step S1-2 is obtained is placed in fluid bed, the second suspension that step S2-2 is obtained is sprayed to
It is coated in capsule core, obtains carrying pill.
9. the preparation method of omeprazole enteric-coated capsules according to claim 8, it is characterised in that：
S2-1：Purified water is added in hydroxypropyl methyl cellulose, is stirred to complete swelling, is configured to fine containing 10% hydroxypropyl methyl
The plain aqueous solution of dimension.
10. the preparation method of omeprazole enteric-coated capsules according to claim 1, it is characterised in that：The first time intestines
Molten clothing, the first enteric layer weightening 30~35%；Second of enteric coating, the second enteric layer weightening 10~15%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113101276A (en) * | 2021-03-11 | 2021-07-13 | 浙江康德药业集团股份有限公司 | Esciprazole magnesium enteric-coated pellet and capsule and preparation method thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1187599A1 (en) * | 1999-06-22 | 2002-03-20 | Dexcel Ltd. | Stable benzimidazole formulation |
| CN1985822A (en) * | 2006-12-14 | 2007-06-27 | 湖南康普制药有限公司 | Enteric omeprazole micropill and its preparing method |
| CN100469366C (en) * | 2001-07-16 | 2009-03-18 | 阿斯特拉曾尼卡有限公司 | Pharmaceutical formulation comprising a proton pump inhibitor and antacids |
| CN104546737A (en) * | 2015-01-08 | 2015-04-29 | 浙江长典医药有限公司 | Pellet type omeprazole enteric capsule and preparation method thereof |
| CN105326801A (en) * | 2015-11-26 | 2016-02-17 | 河北神威药业有限公司 | Preparation process and use method of esomeprazole enteric coating solution |
| CN105726488A (en) * | 2014-12-08 | 2016-07-06 | 上海爱科百发生物医药技术有限公司 | Enteric-coated pellet containing respiratory syncytial virus inhibitor and preparation method thereof |
| CN107802612A (en) * | 2017-12-13 | 2018-03-16 | 南京双科医药开发有限公司 | A kind of omeprazole enteric-coated micro-pill, capsule and preparation method thereof |
-
2018
- 2018-03-29 CN CN201810268484.6A patent/CN108434117A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1187599A1 (en) * | 1999-06-22 | 2002-03-20 | Dexcel Ltd. | Stable benzimidazole formulation |
| CN100469366C (en) * | 2001-07-16 | 2009-03-18 | 阿斯特拉曾尼卡有限公司 | Pharmaceutical formulation comprising a proton pump inhibitor and antacids |
| CN1985822A (en) * | 2006-12-14 | 2007-06-27 | 湖南康普制药有限公司 | Enteric omeprazole micropill and its preparing method |
| CN105726488A (en) * | 2014-12-08 | 2016-07-06 | 上海爱科百发生物医药技术有限公司 | Enteric-coated pellet containing respiratory syncytial virus inhibitor and preparation method thereof |
| CN104546737A (en) * | 2015-01-08 | 2015-04-29 | 浙江长典医药有限公司 | Pellet type omeprazole enteric capsule and preparation method thereof |
| CN105326801A (en) * | 2015-11-26 | 2016-02-17 | 河北神威药业有限公司 | Preparation process and use method of esomeprazole enteric coating solution |
| CN107802612A (en) * | 2017-12-13 | 2018-03-16 | 南京双科医药开发有限公司 | A kind of omeprazole enteric-coated micro-pill, capsule and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 郑俊民主编: "《高分子材料学（第3版）》", 31 January 2009 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113101276A (en) * | 2021-03-11 | 2021-07-13 | 浙江康德药业集团股份有限公司 | Esciprazole magnesium enteric-coated pellet and capsule and preparation method thereof |
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