CN105055350A - Preparation method of proton pump inhibitor-containing tablet - Google Patents
Preparation method of proton pump inhibitor-containing tablet Download PDFInfo
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Abstract
The invention relates to the technical field of medicine preparations and concretely relates to a preparation method of a proton pump inhibitor-containing tablet. The proton pump inhibitor-containing tablet is prepared from controlled release pellets, diluents, a disintegrating agent and a lubricant by a direct tabletting method. The preparation method comprises 1, preparing pellet cores for carrying drugs, 2, preparing isolation pellets, 3, preparing controlled release pellets, 4, carrying out mixing and sieving to obtain a material, and 5, carrying out direct tabletting, wherein in the step 4, a diluent with small particle sizes and the controlled release pellets are mixed and then the mixture and a diluent with big particle sizes are mixed, and the diluents with small and big particle sizes are respectively selected from one or more of cellulose materials. The preparation method solves the problem of poor content uniformity of the existing controlled release pellet roundness excess direct tabletting method so that tablet quality is guaranteed.
Description
Technical field
The present invention relates to pharmaceutical preparations technology field, be specifically related to a kind of preparation method of the tablet containing proton pump inhibitor.
Background technology
Oral sustained-release preparation, due to the advantage of its uniqueness, becomes increasingly conspicuous in the status of art of pharmacy.Multiunit oral sustained-release preparation is a kind of new medicinal preparation technology grown up this year.Because it can effectively avoid because of the too high zest to absorption site mucosa of local drug concentration, reduce toxic and side effects, improve drug absorption, improve bioavailability; Ensure that the safety of medication is avoided dosage to dash forward and released; Reduce the difference in the individuality that causes because of feed and gastric emptying etc. and between individuality.
Multiunit controlled release formulations for oral administration can enable active substance be sent to the gastrointestinal tract site that can absorb rapidly by complete, and protection medicine exempts from the destruction of gastric acid.
Disclose the controlled release preparation of polytype multiple-unit dosage form in the prior art, its preparation technology adopts compaction of pellet technology.But there is various problem when the piller being surrounded by clothing film is pressed into tablet.As functional protection clothing is broken after pressurized, it is caused to be destroyed by the gastro-intestinal Fluid permeated.In addition, micropill roundness is high, excess liquidity, easily occurs that material layering causes product content homogeneity question in tableting processes.
Patent documentation CN95190819.7 discloses the multiple unit pharmaceutical preparation containing proton pump inhibitor.Said preparation is by spray packaging technique at the bottom of celphere or extrusion spheronization is obtained carries a pill core, and end spray coating obtains controlled release micro pill, then with tableting aid or blank granules mixed pressuring plate.The controlled release micro pill roundness that end spray packaging technique obtains is high, after simply mixing with microcrystalline Cellulose, will occur uniformity of dosage units problem.Plastic material microcrystalline cellulose is adopted usually to improve the toughness of micropill in extrusion spheronization method, but extrusion spheronization complex process, influence factor is various, the yield of useful piller is very low, particularly prepared micropill particle size distribution can produce significant impact to product quality, is unfavorable for the quality control of the large production of commercialization.In addition, protect micropill not crushed in tableting processes by blank granules.Because some factor needs to rely on micro-judgment, therefore may cause unstable product quality, between batch, difference is large etc.
Therefore, be necessary develop can overcome above-mentioned prior art defect, manufacturing process is simple, cost is low, product quality meets the requirements and stable tabletting method and corresponding prescription.
Summary of the invention
For above the deficiencies in the prior art, the object of this invention is to provide a kind of preparation method of the tablet containing proton pump inhibitor.The present inventor is surprised to find that in an experiment, and for proton pump inhibitor, the tablet obtained by preparation method direct compression of the present invention, can improve the defect of prior art tablet completely; The tablet adopting preparation method of the present invention obtained can Stable Release active component, and complete is sent to absorption site; Not only significantly reduce production cost, and drug bioavailability and stability can be improved, and overcome the problem of the uniformity of dosage units difference existing for direct compression process preparation of controlled release micro pill rounding property surplus, make tablet quality more guaranteed.
For achieving the above object, the preparation method of the tablet containing proton pump inhibitor provided by the invention, wherein, described tablet is prepared by direct compression process by the component of following mass percent:
Described preparation method comprises the following steps:
(1) pill core is carried in surface preparation proton pump inhibitor being wrapped in celphere; Wherein, the mass ratio of described proton pump inhibitor and celphere is 0.4 ~ 1:1;
(2) to above-mentioned year pill core bag contagion gown preparation isolation piller; The weight of described contagion gown is 40% ~ 60% of described year pill core weight;
(3) controlled release micro pill is prepared to above-mentioned isolation piller is enteric coated; The weight of described enteric coating is 55% ~ 75% of described isolation pellet weight;
(4) by described controlled release micro pill, diluent, disintegrating agent and mix lubricant, sieving obtains material;
(5) by above-mentioned material direct compression, described tablet is obtained;
In described step (4), described mixing is first mixed with controlled release micro pill by diluent less for particle diameter; Again by this mixture and the larger mixing diluents of particle diameter; The diluent that described particle diameter is less and the larger diluent of particle diameter are selected from one or more of cellulose family.
Preferably, in described step (4), described mixing is specially:
By diluent less to described controlled release micro pill, particle diameter and disintegrating agent mixing, sieving obtains mixture, then by this mixture, mixing diluents that particle diameter is larger, then with sieve after mix lubricant obtain material; Or,
By described controlled release micro pill and the less mixing diluents of particle diameter, sieving obtains mixture, then by diluent larger to this mixture, particle diameter and disintegrating agent mixing, then with sieve after mix lubricant obtain material.
Preferably, the diluent that described particle diameter is less and the larger diluent of particle diameter are microcrystalline Cellulose (preferably can direct compression type).
More preferably, the diluent that described particle diameter is less is microcrystalline Cellulose PH101; The diluent that described particle diameter is larger is microcrystalline Cellulose PH200.
Further preferably, the particle diameter of described microcrystalline Cellulose PH101 is 30 ~ 50 μm; The particle diameter of described microcrystalline Cellulose PH200 is 180 ~ 200 μm.
Preferably, the mass ratio of described microcrystalline Cellulose PH101 and microcrystalline Cellulose PH200 is 1:0.4 ~ 4.
More preferably, the mass ratio of described microcrystalline Cellulose PH101 and microcrystalline Cellulose PH200 is 1:0.5 ~ 3.
In one embodiment, the mass ratio of described microcrystalline Cellulose PH101 and microcrystalline Cellulose PH200 is 1:2.
Wherein, described " diluent that particle diameter is less " compares with selected all diluent, but the mobility not affecting prescription suitable is as the criterion.
Preferably, in described " diluent that particle diameter is less mixes with controlled release micro pill ", incorporation time is 5 ~ 20 minutes, and mixing velocity is 5 ~ 30 revs/min.Preferably, incorporation time is 10 ~ 15 minutes, and mixing velocity is 10 ~ 25 revs/min.In one embodiment of the invention, incorporation time is 10 minutes, and mixing velocity is 10 revs/min.
Preferably, in described " by this mixture and the larger mixing diluents of particle diameter ", incorporation time is 5 ~ 20 minutes, and mixing velocity is 5 ~ 30 revs/min.Preferably, incorporation time is 10 ~ 15 minutes, and mixing velocity is 10 ~ 25 revs/min.In one embodiment of the invention, incorporation time is 15 minutes, and mixing velocity is 10 revs/min.
The diluent that the present invention selects particle diameter different, object is wrapped up by controlled release micro pill by the diluent (such as microcrystalline Cellulose PH101) that particle diameter is less, then mix with other adjuvants, ensures content and the uniformity of dosage units of tablet.
In described step (4), described controlled release micro pill can sieve by the screen sizes used of sieving smoothly; Preferably, the screen cloth being greater than the grain size of described controlled release micro pill is used; In one embodiment of the invention, the screen cloth slightly larger than described controlled release micro pill grain size is used.
Described mixing can be joined in blender by material to mix.
Preferably, described lubricant is what sieve in advance, and described screen cloth is generally 16 ~ 30 orders, is preferably 16 ~ 25 orders, is more preferably 20 orders.
Preferably, in described step (5), suitably regulate tableting pressure, make the tablet friability of compacting qualified, ensure that product does not occur sliver problem in transportation.
Described celphere is that the art is known, can adopt as sucrose ball core, sucrose starches ball core, lactose ball core etc., is preferably sucrose ball core.
The particle diameter of described celphere is 0.20 ~ 0.36mm, is preferably 0.212 ~ 0.355mm.
Preferably, the mass ratio of described proton pump inhibitor and celphere is 0.8 ~ 1:1; Be more preferably 1:1.
Preferably, in step (1), described parcel is dissolved in proton pump inhibitor or is suspended in wiring solution-forming or suspension in binder solution, is wrapped on celphere by end spray coating method; Described binding agent is hypromellose (being preferably hypromellose E5).Described binder solution is aqueous solution, and its concentration is preferably 5% (W/V).
For multiunit preparation, according to direct compression process, the tablet content uniformity problems being difficult to overcome may be there is.The present invention is by selecting the material with suitable mobility, and suitable hybrid mode ensures the uniformity of dosage units of tablet prepared by direct powder compression.
Term " suitable mobility " refers generally to powder mixture and can rapidly and flow equably, thus can be filled in punch die equably.
Specifically, the material that the present invention has a suitable mobility has composition as above and formula.
Term " suitable hybrid mode " refers generally to hybrid mode used can be made the uniformity of dosage units of obtained tablet meet the requirements or reach higher level.
For tablet of the present invention, in order to prevent controlled release micro pill excess liquidity, adopting a point step mixing process, namely with the microcrystalline Cellulose that particle diameter is less, controlled release micro pill being wrapped up, thus avoid controlled release micro pill uneven distribution and affect uniformity of dosage units.In addition, the microcrystalline Cellulose that particle diameter is larger bears certain pressure when tabletting, thus ensures that controlled release micro pill is not crushed, the stability that the anti-pressure ability improving controlled release micro pill with this is become reconciled.
The present invention is also by mixed process, and adopt screen method, sieved by the material of premixing, prevent fine powder from boning, controlled release micro pill is better disperseed, the uniformity of dosage units of compressed tablet is good.
Active component in tablet of the present invention is proton pump inhibitor, and it is mainly used in treating the digestive system disorder disease relevant with gastric acid, the lansoprazole of such as known name, pantoprazole, omeprazole or esomeprazole etc.But due to the existence of sulfoxide group in structure, extremely responsive in acid medium, easily by acid compound catalysis fast degradation.
React with acid enteric coating material to isolate active component, affect stability, improve the toughness of controlled release micro pill simultaneously, ensure that product has good acid-fast ability, the present invention is to carrying pill core parcel enteric coating (clothing film layer) front step of carrying out bag contagion gown.
The material of described contagion gown is coating material/binding agent and optional antiplastering aid.The material of described contagion gown is also unrestricted, can be the conventional coating material in this area, as one or more in low viscous hypromellose, polyvidone, hydroxypropyl cellulose, ethyl cellulose etc.Conventional antiplastering aid can also be added, as one or more in Pulvis Talci, glyceryl stearate, silicon dioxide and magnesium stearate etc. simultaneously.
The coating material of described contagion gown and the usage ratio of antiplastering aid are also without any restriction, and it can be that ratio is commonly used in this area.Preferably, the weight ratio of described coating material and antiplastering aid is 8 ~ 10:17.5.
As preferably, described sealing coat comprises coating material and antiplastering aid; Described coating material is hypromellose E5, and antiplastering aid used is Pulvis Talci and magnesium stearate.
Preferably, the weight of described contagion gown is 45% ~ 55% of described year pill core weight, is more preferably about 50%.
The component of described enteric coating is well known in the art, generally comprises enteric material, plasticizer, antiplastering aid and surfactant etc.Wherein select situation to determine whether to add as these components such as plasticizer and surfactant need to look enteric material, this is also general knowledge known in this field.Described enteric material, plasticizer, antiplastering aid and surfactant etc. all can adopt material well-known in the art.
Preferably, described enteric material comprises crylic acid resin, cellulose acetate-phthalate, hydroxypropyl methyl cellulose phthalate, polyvinyl alcohol phthalate ester, cellulose acetate benzenetricarboxylic acid ester and Lac etc.; Described plasticizer can be citric acid ester type, phthalate or phosphoric acid ester etc.; Described antiplastering aid can be magnesium stearate or single two glyceryl stearates etc.; Described surfactant is tween 80 or sodium lauryl sulphate etc.More preferably, the weight ratio of described enteric material, plasticizer, antiplastering aid and surfactant is 100:20 ~ 30:2.5 ~ 10:1 ~ 3.
Preferably, described enteric material is polyacrylic acid resin emulsion, and described plasticizer is triethyl citrate, and described antiplastering aid is single two glyceryl stearate, and described surfactant is tween 80.
Preferably, the weight of described enteric coating is 60% ~ 70% of described isolation pellet weight, is more preferably about 65%.
Described disintegrating agent can be one or more in cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium and polyvinylpolypyrrolidone.
Described lubricant can be one or more in magnesium stearate, stearic acid, lauric acid fumaric acid sodium, Pulvis Talci and colloidal silica.
Preferably, described tablet is prepared by direct compression process by the component of following mass percent:
In step (1), the mass ratio of described proton pump inhibitor and celphere is 0.8 ~ 1:1;
In step (2), the weight of described contagion gown is 45% ~ 55% of described year pill core weight; The weight ratio of described coating material and antiplastering aid is 8 ~ 10:17.5;
In step (3), the weight of described enteric coating is 60% ~ 70% of described isolation pellet weight; The weight ratio of described enteric material, plasticizer, antiplastering aid, surfactant is 100:20 ~ 30:2.5 ~ 10:1 ~ 3.
In step (4), the mass ratio of described microcrystalline Cellulose PH101 and microcrystalline Cellulose PH200 is 1:0.5 ~ 3.
More preferably, described tablet is prepared by direct compression process by the component of following mass percent:
In step (1), described celphere is sucrose celphere, and particle diameter is 0.212 ~ 0.355mm; The mass ratio of described proton pump inhibitor and celphere is 1:1; The binding agent that described parcel uses is hypromellose E5;
In step (2), the weight of described contagion gown is 50% of described year pill core weight; Described coating material is hypromellose E5, and described antiplastering aid is Pulvis Talci and magnesium stearate;
In step (3), the weight of described enteric coating is 65% of described isolation pellet weight; Described enteric material is polyacrylic acid resin emulsion; Described plasticizer is triethyl citrate; Described antiplastering aid is single two glyceryl stearate; Described surfactant is tween 80;
In step (4), described disintegrating agent is polyvinylpolypyrrolidone; Described lubricant is magnesium stearate; The mass ratio of described microcrystalline Cellulose PH101 and microcrystalline Cellulose PH200 is 1:2;
In step (5), the hardness of described tablet maintains 80N ~ 100N.
In a detailed description of the invention, described tablet is prepared by direct compression process by the component of following mass percent:
In addition, the invention provides a kind of tablet containing proton pump inhibitor, it is prepared from by above-mentioned preparation method.
The preparation method of direct powder compression of the present invention, gained tablet has following advantage:
1, the prescription of Tablets and preparation method complement each other, influence each other, synergism, effectively control controlled release micro pill excess liquidity problem, thus avoid controlled release micro pill uneven distribution and have impact on the uniformity of dosage units of product, and then affect effectiveness and the safety of product.
2, preparation method of the present invention is simply conducive to industrialized great production, and repeatability is high, and the product formulation obtained has the good advantage of medicine stability.
3, tablet of the present invention has good compressibility, does not affect the hardness of tablet, effectively ensure the integrity in transportation because of the difference of the production capacity of equipment.
4, method for preparing tablet thereof does not use organic solvent, and adjuvant used is all easy acquisitions, cheap, cost of manufacture spends less.
Detailed description of the invention
Those skilled in the art can use for reference present disclosure, and suitable improving technique parameter realizes.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are deemed to be included in the present invention.Product of the present invention and method are described by preferred embodiment, related personnel obviously can not depart from content of the present invention, spirit and scope methods and applications as herein described are changed or suitably change with combination, realize and apply the technology of the present invention.
Just the preparation method of tablet provided by the invention is described further below.
embodiment 1 direct powder compression prepares tablet
Adopt the celphere be purchased, its prescription is as shown in table 1:
Table 1: tablet (microcrystalline cellulose cellulose content 62%) prescription
Celphere is placed in fluid bed (end spray) coating device, with the hypromellose E5 aqueous solution of 5% (W/V) for binding agent, the active component lansoprazole taking recipe quantity adds in hypromellose aqueous solution, fluidisation medicine-feeding is carried out under Keep agitation condition, temperature of charge maintains 35 DEG C ~ 45 DEG C, inlet temperature not higher than 90 DEG C, atomizing pressure 0.15 ~ 0.20Mpa; Obtain carrying pill core.
Take the hydroxypropyl cellulose of recipe quantity, to take water as solvent formulation content be 5% solution, under Keep agitation state, add magnesium stearate and Pulvis Talci successively.By the coating solution Keep agitation of preparation, be sprayed at spray gun and carry on pill core, temperature of charge maintains 35 DEG C ~ 45 DEG C, inlet temperature not higher than 90 DEG C, atomizing pressure 0.15 ~ 0.20Mpa; Obtain isolating piller.
Tween 80 is added to the water and stirs evenly, add single two glyceryl stearate, Keep agitation; Take triethyl citrate, add in suitable quantity of water, homogenize; Pour in tween 80 solution, and slowly pour in the polyacrylic acid resin emulsion under stirring.Isolation piller is placed in fluid bed coating, and temperature of charge maintains 25 DEG C ~ 35 DEG C, inlet temperature not higher than 60 DEG C, atomizing pressure 0.15 ~ 0.20Mpa; Obtain controlled release micro pill.
Be added in blender by microcrystalline Cellulose PH101 (particle diameter is 30 ~ 50 μm) and gained controlled release micro pill, mix 10 minutes, mixing velocity is 10 revs/min; After mixture being crossed 20 mesh sieves, be added in blender with microcrystalline Cellulose PH200 (particle diameter is 180 ~ 200 μm) and polyvinylpolypyrrolidone, mix 15 minutes, mixing velocity is 10 revs/min; Be added in above-mentioned blender by the magnesium stearate after crossing 20 mesh sieves, continue mixing 5 minutes, mixing velocity is 10 revs/min; Obtain material.
Above-mentioned material is put into tablet machine direct compression, and adjustment pressure makes the hardness of tablet maintain 80N ~ 100N, obtains tablet of the present invention.
embodiment 2 direct powder compression prepares tablet
Prescription is as shown in table 2:
Table 2: tablet (microcrystalline cellulose cellulose content 70%) prescription
Technique in the same manner as in Example 1 is adopted to prepare tablet.
embodiment 3 direct powder compression prepares tablet
Prescription is as shown in table 3:
Table 3: tablet (microcrystalline cellulose cellulose content 60%) prescription
Except following step is different from the preparation technology of embodiment 1, technique in the same manner as in Example 1 is adopted to prepare tablet:
Be added in blender by microcrystalline Cellulose PH101 (particle diameter is 30 ~ 50 μm), polyvinylpolypyrrolidone and gained controlled release micro pill, mix 10 minutes, mixing velocity is 10 revs/min; After mixture being crossed 20 mesh sieves, be added in blender with microcrystalline Cellulose PH200 (particle diameter is 180 ~ 200 μm), mix 15 minutes, mixing velocity is 10 revs/min; Be added in above-mentioned blender by the magnesium stearate after crossing 20 mesh sieves, continue mixing 5 minutes, mixing velocity is 10 revs/min; Obtain material.
embodiment 4 direct powder compression prepares tablet
Adopt the celphere be purchased, its prescription is as shown in table 4:
Table 4: tablet (microcrystalline cellulose cellulose content 62%) prescription
Technique in the same manner as in Example 1 is adopted to prepare tablet.
comparative example 1
Except following step is different from the preparation technology of embodiment 1, prescription in the same manner as in Example 1 and technique is adopted to prepare tablet:
Be added in blender by microcrystalline Cellulose PH101, microcrystalline Cellulose PH200, polyvinylpolypyrrolidone and controlled release micro pill, mix 10 minutes, mixing velocity is 10 revs/min; Then magnesium stearate be added in above-mentioned blender, continue mixing 5 minutes, mixing velocity is 10 revs/min; Obtain material.
the tablet acid-resistant strength of EXPERIMENTAL EXAMPLE 1 embodiment 1 ~ 4, comparative example 1 measures
Because active component can decompose in acid, directly cannot measure its burst size in acid, so measure its medicament contg do not discharged, be acid-resistant strength.Get each sample, according to drug release determination method (" Chinese Pharmacopoeia " version in 2010 two annex XD second methods), with hydrochloric acid solution 750mL for solvent, rotating speed 100 revs/min, stops after 2 hours and takes out tablet, detection level.
Table 5 acid-resistant strength assay result
the mensuration of the tablet content uniformity of EXPERIMENTAL EXAMPLE 2 embodiment 1,2,4 and comparative example 1
Example 1,2,4 and each 10 of comparative example 1 product, be placed in 20mL measuring bottle respectively, measures according to " Chinese Pharmacopoeia " 2010 editions annex XE Determination of Content Uniformity methods, calculates content:
Table 6: the uniformity of dosage units of tablet
*: the size of A+1.80S represents the quality of the tablet content uniformity.S is the standard deviation of the relative amount of 10;
A is the absolute value of the difference of labelled amount and average.
As seen from Table 6, when microcrystalline cellulose cellulose content is 60 ~ 70%, the uniformity of dosage units of the compressed tablet after the different microcrystalline Cellulose distributed rendering of particle diameter sieves is fine, and A+1.80S value is lower than 10.50.After the microcrystalline Cellulose that particle diameter is different and controlled release micro pill are mixed together, the value of the A+1.80S of compressed tablet is greater than the value adopting substep blend step.
Therefore, adopt direct compression process compacting multiple-unit preparation, when microcrystalline cellulose cellulose content is 60 ~ 70%, the different microcrystalline Cellulose substep mixing of particle diameter sieve after the uniformity of dosage units of compressed tablet fine.
eXPERIMENTAL EXAMPLE 3 storage stability measures
The compressed tablet of embodiment 1 is packaged in two aluminum, places under 40 DEG C/RH75% condition after 6 months, adopt HPLC analysing impurity content.
Table 7 impurity content
| Embodiment 1 | |
| Total assorted content (%) | 0.00 |
Table 7 shows, in storage stability measures, the product quality of embodiment 1 is constant, and the toughness that contagion gown has good buffer action, the enteric coating of adequate thickness is conducive to controlled release micro pill is described, not easily crush during pressurized, its prescription and preparation method can ensure product stability.
Claims (10)
1. a preparation method for the tablet containing proton pump inhibitor, it is characterized in that, described tablet is prepared by direct compression process by the component of following mass percent:
Described preparation method comprises the following steps:
(1) pill core is carried in surface preparation proton pump inhibitor being wrapped in celphere; Wherein, the mass ratio of described proton pump inhibitor and celphere is 0.4 ~ 1:1;
(2) to above-mentioned year pill core bag contagion gown preparation isolation piller; The weight of described contagion gown is 40% ~ 60% of described year pill core weight;
(3) controlled release micro pill is prepared to above-mentioned isolation piller is enteric coated; The weight of described enteric coating is 55% ~ 75% of described isolation pellet weight;
(4) by described controlled release micro pill, diluent, disintegrating agent and mix lubricant, sieving obtains material;
(5) by above-mentioned material direct compression, described tablet is obtained;
In described step (4), described mixing is first mixed with controlled release micro pill by diluent less for particle diameter; Again by this mixture and the larger mixing diluents of particle diameter;
The diluent that described particle diameter is less and the larger diluent of particle diameter are selected from one or more of cellulose family.
2. the preparation method of the tablet containing proton pump inhibitor according to claim 1, is characterized in that, in described step (4), described in be mixed into:
By diluent less to described controlled release micro pill, particle diameter and disintegrating agent mixing, sieving obtains mixture, then by this mixture, mixing diluents that particle diameter is larger, then with sieve after mix lubricant obtain material; Or,
By described controlled release micro pill and the less mixing diluents of particle diameter, sieving obtains mixture, then by diluent larger to this mixture, particle diameter and disintegrating agent mixing, then with sieve after mix lubricant obtain material.
3. the preparation method of the tablet containing proton pump inhibitor according to claim 1 and 2, is characterized in that, the diluent that described particle diameter is less and the larger diluent of particle diameter are microcrystalline Cellulose; Preferably, the diluent that described particle diameter is less is microcrystalline Cellulose PH101, and the diluent that described particle diameter is larger is microcrystalline Cellulose PH200.
4. the preparation method of the tablet containing proton pump inhibitor according to claim 3, it is characterized in that, the particle diameter of described microcrystalline Cellulose PH101 is 30 ~ 50 μm, and the particle diameter of described microcrystalline Cellulose PH200 is 180 ~ 200 μm; The mass ratio of described microcrystalline Cellulose PH101 and microcrystalline Cellulose PH200 is 1:0.4 ~ 4.
5. the preparation method of the tablet containing proton pump inhibitor according to claim 1, is characterized in that,
In step (1), the particle diameter of described celphere is 0.20 ~ 0.36mm; Described proton pump inhibitor is lansoprazole, pantoprazole, omeprazole or esomeprazole; Described celphere is sucrose ball core, sucrose starches ball core or lactose ball core;
In step (2), described contagion gown comprises coating material and antiplastering aid; Described coating material is one or more in low viscous hypromellose, polyvidone, hydroxypropyl cellulose, ethyl cellulose; Described antiplastering aid is one or more in Pulvis Talci, glyceryl stearate, silicon dioxide and magnesium stearate;
In step (3), described enteric coating comprises enteric material, plasticizer, antiplastering aid and surfactant; Described enteric material is crylic acid resin, cellulose acetate-phthalate, hydroxypropyl methyl cellulose phthalate, polyvinyl alcohol phthalate ester, cellulose acetate benzenetricarboxylic acid ester or Lac; Described plasticizer is citric acid ester type, phthalate or phosphoric acid ester; Described antiplastering aid is magnesium stearate or single two glyceryl stearate; Described surfactant is tween 80 or sodium lauryl sulphate;
In step (4), described disintegrating agent is one or more in cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, polyvinylpolypyrrolidone; Described lubricant is one or more in magnesium stearate, stearic acid, lauric acid fumaric acid sodium, Pulvis Talci and colloidal silica.
6. the preparation method of the tablet containing proton pump inhibitor according to claim 1, is characterized in that,
In described " diluent that particle diameter is less mixes with controlled release micro pill ", incorporation time is 5 ~ 20 minutes, and mixing velocity is 5 ~ 30 revs/min;
In described " by this mixture and the larger mixing diluents of particle diameter ", incorporation time is 5 ~ 20 minutes, and mixing velocity is 5 ~ 30 revs/min;
Described lubricant is what sieve in advance, and described screen cloth is 16 ~ 30 orders.
7. the preparation method of the tablet according to claim 1 or 5 containing proton pump inhibitor, it is characterized in that, described tablet is prepared by direct compression process by the component of following mass percent:
8. the preparation method of the tablet containing proton pump inhibitor according to claim 7, is characterized in that,
In step (1), the mass ratio of described proton pump inhibitor and celphere is 0.8 ~ 1:1;
In step (2), the weight of described contagion gown is 45% ~ 55% of described year pill core weight; The weight ratio of described coating material and antiplastering aid is 8 ~ 10:17.5;
In step (3), the weight of described enteric coating is 60% ~ 70% of described isolation pellet weight; The weight ratio of described enteric material, plasticizer, antiplastering aid and surfactant is 100:20 ~ 30:2.5 ~ 10:1 ~ 3;
In step (4), the mass ratio of described microcrystalline Cellulose PH101 and microcrystalline Cellulose PH200 is 1:0.5 ~ 3.
9. the preparation method of the tablet containing proton pump inhibitor according to claim 1 or 8, it is characterized in that, described tablet is prepared by direct compression process by the component of following mass percent:
In step (1), described celphere is sucrose celphere, and particle diameter is 0.212 ~ 0.355mm; The mass ratio of described proton pump inhibitor and celphere is 1:1; The binding agent that described parcel uses is hypromellose E5;
In step (2), the weight of described contagion gown is 50% of described year pill core weight; Described coating material is hypromellose E5, and described antiplastering aid is Pulvis Talci and magnesium stearate;
In step (3), the weight of described enteric coating is 65% of described isolation pellet weight; Described enteric material is polyacrylic acid resin emulsion; Described plasticizer is triethyl citrate; Described antiplastering aid is single two glyceryl stearate; Described surfactant is tween 80;
In step (4), described disintegrating agent is polyvinylpolypyrrolidone; Described lubricant is magnesium stearate; The mass ratio of described microcrystalline Cellulose PH101 and microcrystalline Cellulose PH200 is 1:2;
In step (5), the hardness of described tablet maintains 80N ~ 100N.
10. the preparation method of the tablet containing proton pump inhibitor according to claim 9, it is characterized in that, described tablet is prepared by direct compression process by the component of following mass percent:
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105796517A (en) * | 2016-03-22 | 2016-07-27 | 海南华益泰康药业有限公司 | Doxycycline hyclate enteric-coated tablet and preparation method thereof |
| CN106619550A (en) * | 2017-01-20 | 2017-05-10 | 海南华益泰康药业有限公司 | Enteric-coated orally disintegrating tablet containing lansoprazole and preparation method of enteric-coated orally disintegrating tablet |
| CN108201527A (en) * | 2016-12-16 | 2018-06-26 | 广州共禾医药科技有限公司 | A kind of slow-release dry suspension comprising proton pump inhibitor and preparation method thereof |
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| WO2008006534A2 (en) * | 2006-07-11 | 2008-01-17 | Lek Pharmaceuticals D.D. | Multiple unit tablets |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105796517A (en) * | 2016-03-22 | 2016-07-27 | 海南华益泰康药业有限公司 | Doxycycline hyclate enteric-coated tablet and preparation method thereof |
| CN105796517B (en) * | 2016-03-22 | 2019-04-26 | 海南华益泰康药业有限公司 | It is doxycycline hyclate enteric-coated a kind of and preparation method thereof |
| CN108201527A (en) * | 2016-12-16 | 2018-06-26 | 广州共禾医药科技有限公司 | A kind of slow-release dry suspension comprising proton pump inhibitor and preparation method thereof |
| CN106619550A (en) * | 2017-01-20 | 2017-05-10 | 海南华益泰康药业有限公司 | Enteric-coated orally disintegrating tablet containing lansoprazole and preparation method of enteric-coated orally disintegrating tablet |
| CN106619550B (en) * | 2017-01-20 | 2019-08-27 | 海南华益泰康药业有限公司 | A kind of enteric-coated orally disintegrating tablets agent and preparation method thereof containing Lansoprazole |
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|---|---|
| CN105055350B (en) | 2017-12-12 |
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Effective date of registration: 20190612 Address after: 210000 Longmian Avenue 568, High-tech Park, Jiangning District, Nanjing City, Jiangsu Province Patentee after: Nanjing Haijingkang Pharmaceutical Technology Co., Ltd. Address before: 571100 Haikou City, Hainan Province, 273 Nanhai Avenue Haikou High-tech Zone D light steel structure standard industrial plant west side Patentee before: Hainan Visum Pharmaceutical Co., Ltd. |