CN109820832A - Omeprazole enteric-coated ball and preparation method thereof, omeprazole enteric-coated capsules and enteric coatel tablets - Google Patents
Omeprazole enteric-coated ball and preparation method thereof, omeprazole enteric-coated capsules and enteric coatel tablets Download PDFInfo
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Abstract
A kind of omeprazole enteric-coated ball and preparation method thereof, omeprazole enteric-coated capsules and enteric coatel tablets, are related to field of medicaments.Omeprazole enteric-coated ball successively includes: Omeprazole capsule core, separation layer and enteric coating layer from the inside to the outside.Wherein, separation layer and/or enteric coating layer include pH buffer, and pH buffer includes phosphate.Omeprazole enteric-coated ball, omeprazole enteric-coated capsules and enteric coatel tablets, by the way that phosphate pH buffer is arranged in separation layer and/or enteric coating layer, effectively improve the stability of omeprazole enteric-coated ball and guarantees drug effect.The preparation method of omeprazole enteric-coated ball is simple, and operation is controllable, is convenient for industrialized production.
Description
Technical field
This application involves field of medicaments, draw in particular to a kind of omeprazole enteric-coated ball and preparation method thereof, Aomei
Azoles capsulae enterosolubilis and enteric coatel tablets.
Background technique
Omeprazole is the gastric acid proton pump for exclusively acting on parietal cell surface, and the last of gastric acid secretion inhibiting leads to
Road secretes the gastric acid secretion even acid basis that various modes stimulate, there is strong and lasting inhibiting effect.Omeprazole is not
It is only capable of accelerating duodenal ulcer (DU), the healing of gastric ulcer (GU) makes the course for the treatment of shorten 2-4 weeks, and remission is rapid, bursts
Ulcer healing rate is high, and recurrence rate is low.For histamine H2Receptor antagonist and the invalid assistant angstrom syndrome of other drugs treatment, Aomei are drawn
Azoles curative effect is prominent, can many times substitute operative treatment, and patient is made to exempt the hardship of total gastrectomy.Omeprazole treatment is anti-
Fluidity esophagitis, it is histamine H that healing rate, which is more than 80%, in 8 weeks2Twice of receptor antagonist.Omeprazole has become treatment
The choice drug of peptic ulcer (PU).
Since Omeprazole is an alkaline drug, it is unstable in acid, can generate more impurity, mesh because acid destroys
Though preceding destroyed using the gastric acid increased during enteric coating reduction is taken, in the long-term storage process because of the shadow of auxiliary material in prescription
It rings, there are still partial destruction and impurity rise phenomenons, and the side reaction of product is caused to increase.
Summary of the invention
The application provides a kind of omeprazole enteric-coated ball and preparation method thereof, omeprazole enteric-coated capsules and enteric coatel tablets, with
It solves the problems, such as unstable during existing Omeprazole is stored.
It from the inside to the outside successively include: Omeprazole according to the omeprazole enteric-coated ball of the application first aspect embodiment
Capsule core, separation layer and enteric coating layer.
Wherein, separation layer and/or enteric coating layer include pH buffer, and pH buffer includes phosphate.
Firstly, Omeprazole is mainly in small intestinal absorption, Omeprazole Pellets are not broken by gastric acid during taking for guarantee
Bad, can guarantee could discharge, absorbs after it enters duodenum.Take outer enteric-coating layer can be avoided take during Aomei
Azoles is drawn to be destroyed by gastric acid.Again because the pH of existing enteric coating layer is in acidity, is directly contacted with Omeprazole and easily lead to product in life
Appearance degradation destroys in production process, therefore prevents Omeprazole from contacting with the direct of enteric layers using separation layer.
Secondly, Omeprazole is unstable in acid, the pH value of prescription directly influences the sour extent of the destruction of product, therefore
The pH value of final preparation product is controlled by increasing suitable pH buffer in prescription, improves the alkali of omeprazole enteric-coated ball
Degree can effectively reduce product and destroy because degrading caused by acid labile.
Finally, pH buffer is set to separation layer and/or enteric coating layer, on the one hand it is possible to prevente effectively from Omeprazole exists
It is directly mixed during storage with pH buffer, Omeprazole is caused to be partially destroyed, the bad problem of drug effect, on the other hand,
Separation layer and/or the pH buffer of enteric coating layer setting can be reacted with gastric acid, guarantee to enter the Omeprazole before small intestine
Omeprazole in enteric coated pill is in alkaline condition, reduces the loss of Omeprazole as far as possible, guarantees its stability.
Meanwhile phosphatic alkalinity is weaker compared to the highly basic alkalinity such as sodium hydroxide, and Omeprazole can be effectively prevented and exist
Cross unstable, the problem for causing final products content relatively low in the case where alkali.Meanwhile phosphate is compared to carbonate, in acidity
Carbon dioxide will not be discharged under conditions of (gastric acid), guaranteed the integrity degree of separation layer and/or enteric coating layer, be further ensured that Austria
Drug effect when beauty draws azoles enteric coated pill to use.
Wherein, phosphate may include disodium hydrogen phosphate, sodium phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate and biphosphate
One of potassium is a variety of, for example, phosphate be sodium phosphate and sodium dihydrogen phosphate mixture, phosphate can also for sodium phosphate,
Sodium dihydrogen phosphate and the mixture of dipotassium hydrogen phosphate etc..
Optionally, pH buffer includes phosphate-buffered pair, and alkalinity is moderate, effectively adjusts separation layer and/or enteric coating
The pH of layer.Wherein, phosphate-buffered is to for example including sodium dihydrogen phosphate and disodium hydrogen phosphate buffering pair or dipotassium hydrogen phosphate and phosphorus
Acid dihydride potassium buffering equity.
Optionally, the component of phosphate-buffered pair includes disodium hydrogen phosphate and sodium phosphate, wherein disodium hydrogen phosphate and phosphoric acid
The mass ratio of sodium is 1:1-2.1, such as the mass ratio of disodium hydrogen phosphate and sodium phosphate is 1:1,1:1.5,1:1.6,1:1.7,1:
1.8, any one point value in 1:1.9,1:2,1:2.1 or the range between any two points.
Disodium hydrogen phosphate and sodium phosphate buffer pair under the conditions of the ratio, for the pH tune of separation layer and/or enteric coating layer
It is good to save effect, while alkalinity is suitable for, and will not influence the stability of Omeprazole, and the phosphate-buffered end-on acid will not generate
Gas, good stability, effectivelying prevent in transportational process generating gas because meeting acid causes separation layer and/or enteric coating layer loose, leads
The problem of causing omeprazole enteric-coated ball to be lost during transportation.
With reference to first aspect, in some embodiments shown in the application, separation layer includes pH buffer, pH buffer every
Mass percent in absciss layer is 0.8-1.2%；And/or enteric coating layer includes pH buffer, pH buffer is in enteric coating layer
Mass percent is 0.8-1.2%.
In other words, pH buffer can be separately set in separation layer, can also be separately set in enteric coating layer, can be with
Exist simultaneously in separation layer and enteric coating layer, no matter which kind of, pH buffer in enteric coating layer mass percent be 0.8-
1.2%, for example, pH buffer in enteric coating layer mass percent be 0.8%, 0.9%, 1.0%, 1.05%, 1.1%,
The value range between any point or any two points in 1.2%.PH buffer mass percent in isolation layer by layer is 0.8-
1.2%, such as mass percent is 0.8%, 0.9%, 1.0%, 1.05%, 1.1%, 1.2% to pH buffer in the isolation layer
In any point or any two points between value range.
Optionally, separation layer and enteric coating layer include pH buffer, can more effectively carry out the adjustment of pH, further
The stability for guaranteeing Omeprazole in transmission process or storing process, improves its drug effect.
Optionally, Omeprazole capsule core can directly be mixed by pharmaceutically acceptable auxiliary material with Omeprazole, and extruding is made
Ball.But in which, since carrier is directly mixed with Omeprazole, because being influenced by auxiliary material, there are long term storage partial destructions
And impurity rise phenomenon, and the problem of cause the side reaction of product to increase.
Therefore, with reference to first aspect, in some embodiments shown in the application, Omeprazole capsule core includes blank capsule core,
And it is coated on the Omeprazole layer on the surface of blank capsule core.
Under the conditions of the setting, while Omeprazole being carried on blank capsule core, Omeprazole and sky are reduced to the greatest extent
Contact between the raw material of white capsule core avoids the influence of the raw material because of blank capsule core, leads to long term storage part that may be present
Destruction and impurity rise phenomenon.
Optionally, blank capsule core is, for example, sugar-pill, and not only load effect is good, while will not be to the stability of Omeprazole
Cause adverse effect.
According to the preparation method of the omeprazole enteric-coated ball of the application second aspect embodiment comprising following steps:
Spacer layer coating liquid is sprayed to the outer wall of Omeprazole capsule core, to form first pill with separation layer；
Enteric coating layer coating solution is sprayed to the outer wall of the first pill, there is the omeprazole enteric-coated of enteric coating layer to be formed
Ball；
Wherein, spacer layer coating liquid and/or enteric coating layer coating solution include pH buffer, and pH buffer includes phosphate.
According to the preparation method of the omeprazole enteric-coated ball of the application second aspect embodiment, spacer layer coating liquid is utilized
And/or enteric coating layer coating solution includes pH buffer, obtains the omeprazole enteric-coated of the application first aspect offer by spraying
Ball.
It should be noted that the application does not limit the specific ingredient and ratio of spacer layer coating liquid, enteric coating layer coating solution
Example, can refer to the relevant technologies, as long as it includes pH buffer, pH buffer includes phosphate, all falls within the protection model of the application
In enclosing.
Wherein, the mode of spraying is for example, by using spraying spraying, simultaneously, it should be noted that according to the application second aspect
The omeprazole enteric-coated ball provided makes ball mode, and the mode of ball is made using fluidisation, that is to say, using fluidized bed, leads to
It crosses and Omeprazole capsule core is placed in fluidized bed, spacer layer coating can be sprayed by bottom inflow, top spray or bottom screens plate
Liquid when use (spacer layer coating liquid includes adhesive and spacer layer coating basal liquid, spray into simultaneously) and/or enteric coating layer coating
Liquid (enteric coating layer coating solution includes adhesive and enteric coating layer coating basal liquid, and when use sprays into simultaneously) mode is coated and makes
Ball work.
Optionally, the step of spacer layer coating liquid being sprayed at the outer wall of Omeprazole capsule core include:
Omeprazole capsule core is placed on air distribution plate, is driven in Omeprazole capsule core by the air-flow inputted through air distribution plate
It rises, sprays spacer layer coating liquid.
Wherein, air distribution plate is set to fluidized bed, makes ball for fluidizing, wherein can pass through bottom inflow, top spray or bottom
Sieve tray sprays into spacer layer coating liquid mode and is coated work.
Optionally, using bottom inflow, top spray spacer layer coating liquid mode is coated work.
It should be noted that existing mode can be directly used in bottom inflow, that is to say using air distribution plate vertical air inlet
Mode so that Omeprazole capsule core ramps.
Still optionally further, air distribution plate is distributed with multiple air inlets, and multiple air inlets are configured to make the air-flow entered be in
Helical form rises, to drive Omeprazole capsule core spiral.
Air-flow forms helical form and rises form, can drive Omeprazole capsule core spiral, keep Omeprazole capsule core equal
It is even to be distributed in fluidized bed and come into full contact with spacer layer coating liquid, uniformly spray spacer layer coating liquid in Omeprazole ball
The surface of core, while rising form air-flow in the shape of a spiral is evenly distributed on the first pill obtained after spraying spacer layer coating liquid
Fluidized bed effectively avoids the first pill of coating process from being sticked together compared to existing vertical air-flow, guarantees in coating process
The clothing layer uniformity of separation layer reduces the dosage of spacer layer coating liquid, to guarantee the quality of final products.
Optionally, the step of enteric coating layer coating solution being sprayed at the outer wall of the first pill include:
First pill is placed on air distribution plate, drives the first pill to rise by the air-flow inputted through air distribution plate, and spray
Enteric coating layer coating solution.
Wherein, air distribution plate is set to fluidized bed, makes ball for fluidizing, wherein can pass through bottom inflow, top spray or bottom
Sieve tray sprays into enteric coating layer coating solution mode and is coated work.
Optionally, using bottom inflow, top spray enteric coating layer coating solution mode is coated work.
Still optionally further, air distribution plate is distributed with multiple air inlets, and multiple air inlets are configured to make the air-flow entered be in
Helical form rises for driving the first pill spiral.
Air-flow forms helical form and rises form, can drive the first pill spiral, be evenly distributed on the first pill
It is come into full contact in fluidized bed and with enteric coating layer coating solution, uniformly sprays enteric coating layer coating solution in the table of the first pill
Face, while rising form air-flow in the shape of a spiral is uniformly distributed the omeprazole enteric-coated ball obtained after spraying enteric coating layer coating solution
It effectively avoids the omeprazole enteric-coated ball of coating process from being sticked together compared to existing vertical air-flow in fluidized bed, guarantees packet
The clothing layer uniformity of enteric coating layer during clothing reduces the dosage of enteric coating layer coating solution, to guarantee the quality of final products.
It should be noted that the first pill needs after the drying, then carry out spraying enteric coating layer coating solution.
It should be noted that the fluidized bed used in the step of spacer layer coating liquid is sprayed at Omeprazole capsule core and general
The fluidized bed setting used in the step of enteric coating layer coating solution is sprayed at the first pill is identical, that is to say, adopts in two steps
The set-up mode of air distribution plate is identical.
In conjunction with second aspect, in some embodiments shown in the application, the opening direction of air inlet and the center of air distribution plate
Angle between line is greater than 30 ° and less than 40 °, for example, air inlet opening direction and air distribution plate center line between angle be
The value range between any point and any two points in 33 °, 34 °, 35 °, 36 °, 37 ° and 38 °.Within the scope of this, air-flow point
Cloth is uniform, and coated granule (in the application, coated granule refers to Omeprazole capsule core, the first pill and omeprazole enteric-coated ball) spiral shell
It screws on to rise and be evenly distributed in fluidized bed, to guarantee that (in the application, clothing layer includes separation layer and enteric to coating process underpants layer
Clothing layer) consistency of thickness, guarantee the quality of final products.
Optionally, air inlet radially distributes along the center line of air distribution plate；Under the conditions of the setting, air-flow can effectively ensure that
The uniformity of distribution.
Optionally, the cross section of air inlet is in a strip shape.
It is provided according to the omeprazole enteric-coated capsules that the application third aspect embodiment provides, including the application first aspect
Omeprazole enteric-coated ball and capsule shells, omeprazole enteric-coated ball be loaded into capsule shells.
By the setting of capsule shells, further decreases Omeprazole and destroyed because degrading caused by acid labile, effectively protected
The quality of product is demonstrate,proved.
According to the Omeprazole Enteric-coated Tablets that the application fourth aspect embodiment provides, including by pharmaceutically acceptable carrier
Buffering particle obtained, the omeprazole enteric-coated ball and buffering particle that Omeprazole Enteric-coated Tablets are provided by the application first aspect mix
After conjunction, obtained by tabletting.
Wherein, it should be noted that pharmaceutically acceptable carrier is, for example, in disintegrating agent, diluent, lubricant etc.
It is one or more, it does not do specifically repeat herein.
The additional aspect and advantage of the application will be set forth in part in the description, and will partially become from the following description
It obtains obviously, or recognized by the practice of the application.
Detailed description of the invention
Technical solution in ord to more clearly illustrate embodiments of the present application, below will be to needed in the embodiment attached
Figure is briefly described, it should be understood that the following drawings illustrates only some embodiments of the application, therefore is not construed as pair
The restriction of range for those of ordinary skill in the art without creative efforts, can also be according to this
A little attached drawings obtain other relevant attached drawings.
Fig. 1 is the structural schematic diagram for the air distribution plate that the embodiment of the present application 1 provides；
Fig. 2 is the diagrammatic cross-section for the air distribution plate that the embodiment of the present application 1 provides；
Fig. 3 is the diagrammatic cross-section of existing air distribution plate；
Fig. 4 is the appearance diagram of omeprazole enteric-coated ball made from control group 9；
Fig. 5 is the appearance diagram of omeprazole enteric-coated ball made from control group 10；
Fig. 6 is the appearance diagram of omeprazole enteric-coated ball made from control group 11；
Fig. 7 is the appearance diagram of omeprazole enteric-coated ball made from control group 12.
Icon: 10a- air distribution plate；10b- air distribution plate；111- first surface；112- second surface；113- air inlet.
Specific embodiment
It, below will be in the embodiment of the present application to keep the purposes, technical schemes and advantages of the embodiment of the present application clearer
Technical solution be clearly and completely described.The person that is not specified actual conditions in embodiment, according to normal conditions or manufacturer builds
The condition of view carries out.Reagents or instruments used without specified manufacturer is the conventional production that can be obtained by commercially available purchase
Product.
In this application, term " first ", " second ", " third " etc. are only used for distinguishing description, and should not be understood as indicating
Or imply relative importance.
Embodiment 1
Fig. 1 and Fig. 2 is please referred to, the application provides a kind of air distribution plate 10a, for being installed on fluidized bed (not shown),
Fluidisation, which is carried out, in coating bucket (not shown) makes ball.
Air distribution plate 10a has the first surface 111 and second surface 112 being oppositely arranged, and air distribution plate 10a is distributed with multiple
Air inlet 113, each air inlet 113 run through first surface 111 and second surface 112, for be connected to first surface 111 and
Second surface 112 allows wind to be delivered to second surface 112 through air inlet 113 through first surface 111.
Referring to Fig. 3, the centerline parallel of the opening direction of the air inlet 113 of existing air distribution plate 10b and air distribution plate 10b
Setting, that is to say, the axis of air inlet 113 enters perpendicular to first surface 111 and second surface 112 through air inlet 113
Air-flow is linear,, will be to using bottom air inlet inventors have found that in coating process so as to linearly rise to coated granule
Coated granule vertically directly blows to the side far from air distribution plate 10b, while treating coated granule by the way of top spray coating solution
It is coated processing, that is to say and spray coating solution by the way of liquidating, is not only easy to make to be coated with the coated granule of coating solution
Mutual adhesion leads to clothing layer uneven thickness, while the setting to liquidate, due to the not set air inlet of air distribution plate 10b portion
113, simultaneously because air-flow vertical motion, therefore will lead to part coating solution and directly drip in air distribution plate 10b, the dosage of coating solution
Larger, there is also the above problems in such a way that coating solution is sprayed at bottom.
Based on the above issues, improved air distribution plate 10a is inventors herein proposed, makes gas can be with after the entrance of air inlet 113
The spiral for forming air-flow is driven by the spiral of air-flow and is risen in the shape of a spiral to coated granule, while using top spray coating solution
Mode is coated processing, and on the one hand spiralling to coated granule, motion profile is long in fluidized bed, and then the flotation time
It is long, it can adequately can be contacted with coating solution, while spiralling air-flow can drive coated granule to roll, and make wait be coated
The surface of particle further comes into full contact with coating solution, keeps the clothing layer to be formed more uniform, and spiralling air-flow can have
Effect prevents coating solution from directly falling on the position of the not set air inlet 113 of air distribution plate 10a, is wrapped in it effectively wait be coated
The surface of grain, effectively reduces the dosage of coating solution and improves the utilization rate of coating solution.
Wherein, referring to Fig. 2, the angle between the opening direction of air inlet 113 and the center line of air distribution plate 10a is greater than
30 ° and less than 40 °；The angle is indicated with α in Fig. 3.
Optionally, the angle between the opening direction of air inlet 113 and the center line of air distribution plate 10a be 33 °, 34 °, 35 °,
The value range between any point and any two points in 36 °, 37 ° and 38 °.Within the scope of this, air flow method is uniform, makes to be coated
It particle spiral and is evenly distributed in fluidized bed, to guarantee the consistency of thickness of coating process underpants layer, guarantees final
The quality of product.Meanwhile the angle between the opening direction of air inlet 113 and the center line of air distribution plate 10a is greater than 30 ° and is less than
40 °, it is ensured that spiralling coated granule will not be contacted with the peripheral wall of coating bucket, cause coated granule broken.
It should be noted that the opening direction in the application is equal with air inlet tangential angle, air inlet tangential angle that is to say
Angle between the center line of air distribution plate 10a is greater than 30 ° and less than 40 °.
In the present embodiment, the angle between the opening direction of air inlet 113 and the center line of air distribution plate 10a is 35 °, air-flow
It is distributed most uniform.
It should be noted that the opening direction of each air inlet 113 should be along air distribution plate 10a's in multiple air inlets 113
Center line is in counterclockwise or to rotate clockwise, and then keep the spiral air flow to be formed good.
Wherein, air inlet 113 can be distributed in air distribution plate 10a in turbine-like, can also be in array distribution.Optionally, originally
In embodiment, air inlet 113 radially distributes along the center line of air distribution plate 10a.
Air distribution plate 10a can be rectangle, diamond shape, round or ellipse etc., those skilled in the art in the projection of horizontal plane
It can be set according to the actual situation.In the present embodiment, air distribution plate 10a is projected as circle horizontal plane, can make air-flow more
It is uniform.
The section of air inlet 113 can be circle, rectangle, arcuation, diamond shape etc., and optionally, the section of air inlet 113 is item
Shape, wherein the length direction of strip radially distributes along the center line of air distribution plate 10a.For the ease of intuitively observing air inlet
Hole 113 indicates air inlet 113 in the distribution of air distribution plate 10a with linear in Fig. 1.
Embodiment 2
A kind of omeprazole enteric-coated ball, omeprazole enteric-coated ball successively include: Omeprazole capsule core, separation layer from the inside to the outside
And enteric coating layer.
Wherein, Omeprazole capsule core includes blank capsule core, and is coated on the Omeprazole layer on the surface of blank capsule core.
Separation layer includes pH buffer, and the mass percent of pH buffer in the isolation layer is 1%.Enteric coating layer also includes
PH buffer, pH buffer mass percent in enteric coating layer is 1%.
In the present embodiment, pH buffer is the disodium hydrogen phosphate and sodium phosphate that mass ratio is 1:2.
Embodiment 3
A kind of omeprazole enteric-coated ball, omeprazole enteric-coated ball successively include: Omeprazole capsule core, separation layer from the inside to the outside
And enteric coating layer.
Wherein, Omeprazole capsule core includes blank capsule core, and is coated on the Omeprazole layer on the surface of blank capsule core.
Wherein, separation layer includes pH buffer, and the mass percent of pH buffer in the isolation layer is 1%.Enteric coating layer
It also include pH buffer, pH buffer mass percent in enteric coating layer is 1.05%.
In the present embodiment, pH buffer is the disodium hydrogen phosphate and sodium phosphate that mass ratio is 1:2.
Embodiment 4
A kind of omeprazole enteric-coated ball, omeprazole enteric-coated ball successively include: Omeprazole capsule core, separation layer from the inside to the outside
And enteric coating layer.
Wherein, separation layer includes pH buffer, and the mass percent of pH buffer in the isolation layer is 1%.Enteric coating layer
It also include pH buffer, pH buffer mass percent in enteric coating layer is 1%.
In the present embodiment, pH buffer is the disodium hydrogen phosphate and sodium phosphate that mass ratio is 1:2.
Embodiment 5
A kind of omeprazole enteric-coated ball, omeprazole enteric-coated ball successively include: Omeprazole capsule core, separation layer from the inside to the outside
And enteric coating layer.
Wherein, Omeprazole capsule core includes blank capsule core, and is coated on the Omeprazole layer on the surface of blank capsule core.
Wherein, separation layer includes pH buffer, and the mass percent of pH buffer in the isolation layer is 0.9%.Enteric coating
Layer also includes pH buffer, and pH buffer mass percent in enteric coating layer is 1.1%.
In the present embodiment, pH buffer is the disodium hydrogen phosphate and sodium phosphate that mass ratio is 1:2.05.
Embodiment 6
A kind of omeprazole enteric-coated ball, omeprazole enteric-coated ball successively include: Omeprazole capsule core, separation layer from the inside to the outside
And enteric coating layer.
Wherein, Omeprazole capsule core includes blank capsule core, and is coated on the Omeprazole layer on the surface of blank capsule core.
Separation layer includes pH buffer, and the mass percent of pH buffer in the isolation layer is 1%.Enteric coating layer do not include
PH buffer.
In the present embodiment, pH buffer is the disodium hydrogen phosphate and sodium phosphate that mass ratio is 1:2.1.
Embodiment 7
A kind of omeprazole enteric-coated ball, omeprazole enteric-coated ball successively include: Omeprazole capsule core, separation layer from the inside to the outside
And enteric coating layer.
Wherein, Omeprazole capsule core includes blank capsule core, and is coated on the Omeprazole layer on the surface of blank capsule core.
Separation layer does not include pH buffer.Enteric coating layer includes pH buffer, quality of the pH buffer in enteric coating layer
Percentage is 1%.
In the present embodiment, pH buffer is the disodium hydrogen phosphate and sodium phosphate that mass ratio is 1:2.
Embodiment 8
The application provides a kind of preparation method of omeprazole enteric-coated ball, is used to prepare such as any one reality of embodiment 2-4
The omeprazole enteric-coated ball of example offer is provided.
The preparation method includes:
Omeprazole capsule core is placed on the air distribution plate provided such as embodiment 1, is driven by the air-flow inputted through air distribution plate
Omeprazole capsule core helically rises, while spraying spacer layer coating liquid by spraying by the way of top spray, obtains with separation layer
The first pill.
After the drying of the first pill, it is placed on the air distribution plate provided such as embodiment 1, passes through the air-flow band inputted through air distribution plate
The first pill after dynamic drying helically rises, while enteric coating layer coating solution is sprayed by the way of top spray, obtains Aomei drawing
Azoles enteric coated pill.
Wherein, when preparing the omeprazole enteric-coated ball that embodiment 2 provides, spacer layer coating liquid includes pH buffer,
In, the mass percent of pH buffer in the isolation layer is 1%.Enteric coating layer also includes pH buffer, and pH buffer is in enteric
Mass percent is 1% in clothing layer.
When preparing the omeprazole enteric-coated ball that embodiment 3 provides, spacer layer coating liquid includes pH buffer, wherein pH
The mass percent of buffer in the isolation layer is 1%.Enteric coating layer also includes pH buffer, and pH buffer is in enteric coating layer
Mass percent is 1.05%.
When preparing the omeprazole enteric-coated ball that embodiment 4 provides, spacer layer coating liquid includes pH buffer, wherein pH
The mass percent of buffer in the isolation layer is 1%.Enteric coating layer also includes pH buffer, and pH buffer is in enteric coating layer
Mass percent is 1%.
It is noted that it is 1:2 disodium hydrogen phosphate and sodium phosphate that pH buffer, which is mass ratio,.
Embodiment 9
A kind of omeprazole enteric-coated capsules comprising the omeprazole enteric-coated ball that any one embodiment of embodiment 2-4 provides
And capsule shells, omeprazole enteric-coated ball are loaded into capsule shells.
Embodiment 10
A kind of Omeprazole Enteric-coated Tablets, including particle and embodiment are buffered as made from pharmaceutically acceptable carrier
The omeprazole enteric-coated ball that any one embodiment of 2-4 provides, wherein Omeprazole Enteric-coated Tablets are eased up by omeprazole enteric-coated ball
After rushing particle mixing, obtained by tabletting.
Test example 1
Control group 1-3 is set, wherein the spacer layer coating liquid of control group 1,2,3 includes pH buffer, pH buffer every
Mass percent in absciss layer is 1%；The enteric coating layer coating solution of control group 1,2,3 includes pH buffer, pH buffer every
Mass percent in absciss layer is 1%.
Wherein, control group 1,2,3 the difference is that only: in control group 1, it is 1 that the pH buffer of addition, which is mass ratio:
2 sodium carbonate and sodium bicarbonate, the pH buffer that control group 2 adds are the sodium hydroxide and borax that mass ratio is 1:2, control group
The pH buffer added in 3 is the disodium hydrogen phosphate and sodium phosphate that mass ratio is 1:2.
Based on Omeprazole capsule core, it is coated using the control group 1-3 spacer layer coating liquid provided and enteric coating layer
Liquid is coated operation respectively, and Omeprazole in the sample after visual inspection, and detection coating is carried out to sample after coating
Actual content, the results are shown in Table 1.Wherein, the target content of Omeprazole is 9.7% in the sample after coating.
1 testing result of table
It can be obtained according to table 1, the appearance of control group 1 is poor, and possible cause is sodium carbonate and sodium bicarbonate buffer to being coated
Carbon dioxide can be generated because carbonate is unstable in the process, leads to coating surface out-of-flatness.Aomei in the sample that control group 2 obtains
Draw azoles content lower, possible cause is sodium hydroxide and borax buffering to because sodium hydroxide exists, and Omeprazole is in the feelings for crossing alkali
It is unstable under condition, cause final products content relatively low.Therefore select the buffering effect of disodium hydrogen phosphate and sodium phosphate buffer pair compared with
It is good.
Test example 2
Stability test
Set control group 4-8, wherein the buffer in control group 4-8 successively use mass ratio for 1:0,1:1,1:1.5,
The disodium hydrogen phosphate of 1:2,1:2.1: sodium phosphate is coated, to obtaining in such a way that control group 3 in such as test example 1 uses
Product carry out 3 months accelerated stabilities and investigate.Item of the study on the stability in 30 DEG C ± 2 DEG C of temperature, relative humidity 65% ± 5%
It is carried out under part, inspection target is Omeprazole content.The results are shown in Table 2.
2 stability test result of table
According to table 2,0 month content detection situation of each group sample is almost the same, but after 3 months accelerated stabilities are investigated, right
The content of Omeprazole exists and is decreased obviously in the sample provided according to group 4-6, and possible cause is that the pH of buffer is too low, Bu Nengyou
Effect improves the acidity of prescription, can still have degradation situation after leading to long-time.The product appearance and stability and 0 of control group 7-8
A month almost the same, difficult to understand when that is to say disodium hydrogen phosphate in separation layer and enteric layers and sodium phosphate buffer to for ratio 1:2
Beauty draws the good stability of azoles enteric coated pill, and disodium hydrogen phosphate and sodium phosphate buffer are to for ratio 1:2 and 1:2.1 indifference.
The embodiment 6-7 sample provided is repeated 3 times and carries out above-mentioned 3 months accelerated stabilities investigation, Omeprazole 0 month
Content is investigated than the control group 2-5 and relatively low 0.1-0.2% of control group 8, and by accelerated stability in March, content decline about 0.4%
Left and right, stability are poor compared with other control groups.
Test example 3
The preparation method of the omeprazole enteric-coated ball provided using such as embodiment 8 fluidizes pill.Control group 9-12 is set,
In, the difference of control group 9-12 is only that the difference of air inlet tangential angle, observes the obtained sample of control group 9-12, ties
Fruit is as shown in table 3 and Fig. 4-7.
Wherein, Fig. 4 is the appearance diagram of omeprazole enteric-coated ball made from control group 9；Fig. 5 is made from control group 10
The appearance diagram of omeprazole enteric-coated ball, Fig. 6 are the appearance diagram of omeprazole enteric-coated ball made from control group 11, Fig. 7
For the appearance diagram of omeprazole enteric-coated ball made from control group 12.
3 test result of table
In conjunction with table 2 and Fig. 4 to Fig. 7, it can be seen that the effect of control group 11 is best.
To sum up, omeprazole enteric-coated ball, omeprazole enteric-coated capsules and enteric coatel tablets provided by the present application, by prescription
Increase suitable pH buffer to control the stabilization for being conducive to product of the pH value of final preparation product.Meanwhile by pH buffer
It is set to separation layer and/or enteric coating layer, on the one hand it is possible to prevente effectively from Omeprazole is straight with pH buffer during storage
Mixing is connect, Omeprazole is partially destroyed and impurity rise phenomenon, the phenomenon that causing the side reaction of product to increase, on the other hand,
In actual use process, the pH buffer of separation layer and enteric coating layer setting can be reacted with gastric acid, guarantee to enter intestines
The Omeprazole in omeprazole enteric-coated ball before road is in alkaline condition, reduces its Aomei before entering enteron aisle as far as possible and draws
The loss of azoles.The preparation method of omeprazole enteric-coated ball is simple simultaneously, and operation is controllable.
The above is only the alternative embodiments of the application, are not intended to limit this application, for those skilled in the art
For member, various changes and changes are possible in this application.Within the spirit and principles of this application, it is made it is any modification,
Equivalent replacement, improvement etc., should be included within the scope of protection of this application.
Claims (10)
1. a kind of omeprazole enteric-coated ball, which is characterized in that the omeprazole enteric-coated ball successively includes: that Aomei is drawn from the inside to the outside
Azoles capsule core, separation layer and enteric coating layer；
Wherein, the separation layer and/or the enteric coating layer include pH buffer, and the pH buffer includes phosphate.
2. omeprazole enteric-coated ball according to claim 1, which is characterized in that the pH buffer includes phosphate-buffered
It is right；
Optionally, the component of the phosphate-buffered pair includes disodium hydrogen phosphate and sodium phosphate, wherein the disodium hydrogen phosphate and
The mass ratio of sodium phosphate is 1:1-2.1.
3. omeprazole enteric-coated ball according to claim 1, which is characterized in that the separation layer includes pH buffer, institute
Stating mass percent of the pH buffer in the separation layer is 0.8-1.2%；And/or
The enteric coating layer includes pH buffer, and pH buffer mass percent in the enteric coating layer is 0.8-
1.2%.
4. omeprazole enteric-coated ball according to claim 1, which is characterized in that the Omeprazole capsule core includes blank pill
Core, and it is coated on the Omeprazole layer on the surface of the blank capsule core.
5. a kind of preparation method of omeprazole enteric-coated ball according to any one of claims 1-4, which is characterized in that including such as
Lower step:
Spacer layer coating liquid is sprayed to the outer wall of the Omeprazole capsule core, to form first medicine with the separation layer
Ball；
Enteric coating layer coating solution is sprayed to the outer wall of first pill, to form the Aomei with the enteric coating layer
Draw azoles enteric coated pill；
Wherein, the spacer layer coating liquid and/or the enteric coating layer coating solution include pH buffer, and the pH buffer includes
Phosphate.
6. preparation method according to claim 5, which is characterized in that spacer layer coating liquid is sprayed at the Omeprazole
The step of outer wall of capsule core includes:
The Omeprazole capsule core is placed on air distribution plate, the Omeprazole is driven by the air-flow inputted through the air distribution plate
Capsule core rises, and sprays the spacer layer coating liquid；
Optionally, multiple air inlets are distributed in the air distribution plate, and the multiple air inlet is configured to the air-flow for making to enter in spiral shell
It revolves shape to rise, to drive the Omeprazole capsule core spiral.
7. preparation method according to claim 6, which is characterized in that the opening direction of the air inlet and the air distribution plate
Center line between angle be greater than 30 ° and less than 40 °；
Optionally, the air inlet radially distributes along the center line of the air distribution plate；
Optionally, the cross section of the air inlet is in a strip shape.
8. preparation method according to claim 5, which is characterized in that enteric coating layer coating solution is sprayed at first medicine
The step of outer wall of ball includes:
First pill is placed on air distribution plate, is driven on first pill by the air-flow inputted through the air distribution plate
It rises, and sprays the enteric coating layer coating solution；
Optionally, multiple air inlets are distributed in the air distribution plate, and the multiple air inlet is configured to the air-flow for making to enter in spiral shell
Shape is revolved to rise for driving the first pill spiral.
9. a kind of omeprazole enteric-coated capsules, which is characterized in that described in any item omeprazole enteric-coated including claim 1-4
Ball and capsule shells, the omeprazole enteric-coated ball are loaded into the capsule shells.
10. a kind of Omeprazole Enteric-coated Tablets, including particle is buffered as made from pharmaceutically acceptable carrier, which is characterized in that
The Omeprazole Enteric-coated Tablets are mixed by the described in any item omeprazole enteric-coated balls of claim 1-4 and the buffering particle
Afterwards, obtained by tabletting.
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