CN106668017A - Naproxen and esomeprazole magnesium compound enteric-coated capsule and preparation method thereof - Google Patents
Naproxen and esomeprazole magnesium compound enteric-coated capsule and preparation method thereof Download PDFInfo
- Publication number
- CN106668017A CN106668017A CN201510762517.9A CN201510762517A CN106668017A CN 106668017 A CN106668017 A CN 106668017A CN 201510762517 A CN201510762517 A CN 201510762517A CN 106668017 A CN106668017 A CN 106668017A
- Authority
- CN
- China
- Prior art keywords
- naproxen
- enteric
- micropill
- esomeprazole magnesium
- coated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a naproxen and esomeprazole magnesium compound enteric-coated capsule. A content of the capsule is a compound enteric-coated pellet prepared from naproxen and esomeprazole magnesium as active ingredients and pharmaceutic adjuvants. The pellet structurally comprises a blank pellet core, a naproxen drug-containing layer, an isolation layer I, an enteric-coated layer, an isolation layer II, an esomeprazole magnesium drug-containing layer and a color coating layer from inside to outside. A capsule shell preferably selects an HPMC capsule shell. Each capsule contains naproxen of 187.5-250 mg and esomeprazole magnesium (calculated by esomeprazole) of 10 mg, and the two capsules are taken at each time. The release rate of the capsule reaches 85-90 percent; through a stability test under the condition of acceleration, the character, the content, the release degree and related substances of the content are not obviously changed, so that the quality is stable. A preparation method provided by the invention has the benefits that raw materials are easy to obtain, the process is simple, the suitability for large-scale industrial production is realized, and application values are larger.
Description
Technical field
The present invention relates to pharmaceutical preparation, and in particular to compound medicinal formulation, more particularly to a kind of naproxen and the U.S. drawing of Esso
Compound enteric-coated capsule of azoles magnesium and preparation method thereof.
Background technology
Naproxen is a kind of non_steroidal anti_inflammatory drug, English entitled Naproxen, and chemical formula is C14H14O3, molecular weight is
230.259.The treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis is now widely used for, treatment is also used for
The pain caused by various diseases and heating, but it often has a GI bad reaction, serious caused gastroenteritic ulcer and stomach
Bleeding.
Esomeprazole magnesium is a kind of acid secretion inhibitors (proton pump inhibitor), and its mechanism of action is by specificity
Targeting mechanism reduce hydrochloric acid in gastric juice secretion, can control gastric acid secretion, alleviate gastric ulcer symptom, it is anti-that clinic is usually used in stomach oesophagus
The treatment of fluidity disease-erosive reflux esophagitis, and bad reaction is few.Its English entitled Esomeprazole
Magnesium trihydrate, chemical formula is C34H42MgN6O9S2, molecular weight is 767.2, clinically typically adopts its three water
Compound.
FDA (food and medicine Surveillance Authority of the U.S.) has had been approved by a kind of enteric solubility naproxen in May, 2010
(naproxen) and quick-releasing type esomeprazole magnesium (esomeprazole magnesium) Compound Tablet, trade name
Vimovo, (ownership of the commodity is at present by Horizon for AstraZeneca (AstraZeneca) and Pozen companies for manufacturer
Company buys), for treating with the arthritic patient of Associated with non-steroidal Anti-inflammatory Drugs gastric ulcer risk.Clinically, phase
Than in the enteric solubility naproxen of alone daily 2 times, naproxen/esomeprazole magnesium enteric coatel tablets are taken daily 2 times, it is possible to decrease scope
Gastric ulcer incidence under checking.Therefore, during the two combination, the wind of gastric ulcer caused by NSAIDs can be reduced
Danger, is preferably applied to alleviate the symptom of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis etc..And by naproxen
Compound preparation is made with esomeprazole magnesium, is more convenient for taking, the compliance of patient can be improved.
Naproxen esomeprazole magnesium enteric coatel tablets (Vimovo) of FDA approvals, its preparation structure is：With naproxen as core
Piece, wraps 6 layers of clothing, from inside to outside respectively separation layer, enteric layer, separation layer, esomeprazole medicine layer, color clothing layer, outermost
Layer.But, because tablet is in coating, surface may have abrasion, and coating loss of material is larger, and actual coating amount receives technique shadow
Sound is larger, and terminal point control is more difficult, therefore the preparation technique difficulty of esomeprazole magnesium tablet coating medicine-feeding is larger, wayward to contain
Amount and uniformity of dosage units, easily cause quality problems, while having high demands to preparation equipment, therefore have much room for improvement.
The content of the invention
The technical problem to be solved is to overcome above-mentioned weak point, and it is beautiful that research and design can more preferably control Esso
The content and uniformity of dosage units, good stability of azoles magnesium are drawn, and is easy to industrially prepared naproxen and esomeprazole magnesium compound intestines
Colloidal sol capsule.
The present invention provides a kind of naproxen and the compound enteric-coated capsule of esomeprazole magnesium.
Naproxen of the present invention and the compound enteric-coated capsule of esomeprazole magnesium, per 187.5mg- containing naproxen
250mg, containing esomeprazole magnesium (in terms of esomeprazole) 10mg.
The content of naproxen of the present invention and the compound enteric-coated capsule of esomeprazole magnesium is by the naphthalene as active component
General life and esomeprazole magnesium and compound enteric-coated micropill made by pharmaceutic adjuvant, the structure of the compound enteric-coated micropill is from inside to outside
It is followed successively by blank capsule core, naproxen medicated layer, separation layer I, enteric coating layer, separation layer II, esomeprazole magnesium medicated layer and face
Color clothing layer.
When the separation layer I of the compound enteric-coated micropill of the invention can avoid enteric coating, naproxen enters into enteric coating layer,
So as to the enteric for affecting naproxen discharges and stability；Separation layer II can avoid the enteric coating layer of acid structure with the U.S. drawing of Esso
The directly contact of azoles magnesium granules and affect the stability of esomeprazole magnesium.
Compound enteric-coated micropill of the present invention is filled in HPMC capsule shells, compared to gelatine capsule shell (13%-16%
Water content), HPMC softgel shells have water content low, and water vapour transit dose is low, in low-humidity environment hardly under friability and high temperature
The advantages of good stability.Therefore, it can reduce the moisture in esomeprazole magnesium ingress of air and in softgel shell, reduce medicine drop
Solution, improves stability and shelf life；And in drier used in HPDE bottles, it is not result in that softgel shell is hardened embrittlement.
Specifically, naproxen of the present invention and the compound enteric-coated micropill of esomeprazole magnesium, by following weight proportion
Into being grouped into：(in terms of 1000)
(1) the compound enteric-coated micropill of naproxen esomeprazole magnesium:
Preferably, naproxen of the present invention and the compound enteric-coated micropill of esomeprazole magnesium, by following weight proportion
Into being grouped into：(in terms of 1000)
Naproxen of the present invention and the compound enteric-coated micropill of esomeprazole magnesium, blank capsule core (the particle diameter 0.1mm-
0.2mm) it is selected from sucrose capsule core, microcrystalline cellulose capsule core or silica capsule core, preferably sucrose capsule core (particle diameter 0.1mm-
0.2mm)。
Described adhesive is selected from one or more in Hydroxypropyl methylcellulose, PVP or hydroxypropyl cellulose, preferred hydroxyl
Third methylcellulose E5.
The pH adjusting agent is selected from sodium carbonate, sodium acid carbonate, NaOH or magnesia, preferred sodium carbonate.
The softgel shell is selected from gelatin softgel shell or HPMC softgel shells, preferred HPMC softgel shells.
It is a further object of the present invention to provide the preparation method of above-mentioned naproxen and the compound enteric-coated capsule of esomeprazole magnesium,
The method is comprised the following steps：
(1) naproxen is adopted into airslide disintegrating mill micronizing (D90<10 microns), it is standby；
(2) adhesive (25%-45% of total amount) is dissolved under purified water, stirring and is slowly added to step (1) material, continued
Naproxen medicine-feeding suspension is made in stirring；
(3) blank capsule core is put in fluid bed, is preheated to product temperature for 35 DEG C -45 DEG C, sprayed on step (2) naproxen
Medicine suspension, adjusts fluid bed EAT, intake volume, hydrojet speed and atomizing pressure, makes micropill be in fluidized state, no
Adhesion, it is not spray-dried, until medicine-feeding suspension has sprayed, continues to be dried 5-30 minutes, makes micropill moisture<1.5%, obtain naproxen
Micropill；
(4) coating solution of configuration isolation layer I：By adhesive (5%-20% of total amount) and the antiplastering aid (30%- of total amount
60%) in adding the ethanol of 70%-80%, the coating solution of separation layer I is made in persistently stirring；
(5) the naproxen pastille micropill of step (3) is put in fluid bed, is preheated to product temperature for 35 DEG C -45 DEG C, sprayed into
The coating solution of step (4) separation layer I, adjusts fluid bed EAT (45 DEG C -70 DEG C), intake volume (60m3/h-1000m3/h)、
Hydrojet speed (2g/min-250g/min) and atomizing pressure (1bar-3bar), make micropill in fluidized state, adhesion, do not spray
Mist is dried, until separation layer solution or suspension have sprayed, continues to be dried 5-30 minutes, makes micropill moisture<1.5%, isolation must be wrapped
The naproxen coated pellets of layer I；
(6) enteric layer coating solution is configured：Suitable quantity of water (enteric coating liquid adds the 40%-60% of water inventory) is taken, 70 are heated to
DEG C, triethyl citrate and Tween 80 are added, disperseed with dispersion machine, add glycerin monostearate, 10-30 point of dispersion machine dispersion
Clock, adds remaining water, is persistently stirred with mixer, is cooled to 10 DEG C -40 DEG C, then mixes with Utech L30D-55, stirs at a slow speed
Mix, obtain enteric coating liquid；
(7) naproxen coated pellets of the bag separation layer I of step (5) are put in fluid bed, is preheated to product temperature for 25 DEG C -35
DEG C, step (6) enteric coating liquid is sprayed into, adjust fluid bed EAT (35 DEG C -70 DEG C), intake volume (60m3/h-1000m3/
H), hydrojet speed (2g/min-250g/min) and atomizing pressure (1bar-3bar), make micropill in fluidized state, adhesion,
It is not spray-dried, until coating solution has sprayed, continues to be dried 5-30 minutes, makes micropill moisture<1.5%, obtain naproxen enteric-coated micro-pill；
(8) coating solution of configuration isolation layer II：By adhesive (5%-20% of total amount) and the antiplastering aid (50%- of total amount
70%) it is dissolved in the ethanol of 70%-80%, the coating solution of separation layer II is made in persistently stirring；
(9) step (7) naproxen enteric-coated micro-pill is put in fluid bed, is preheated to product temperature for 35 DEG C -45 DEG C, spray into step
Suddenly the coating solution of (8) separation layer II, adjusts fluid bed EAT (45 DEG C -70 DEG C), intake volume (60m3/h-1000m3/ h), spray
Liquid speed degree (2g/min-250g/min) and atomizing pressure (1bar-3bar), make micropill in fluidized state, adhesion, do not spray
It is dried, until separation layer solution or suspension have sprayed, continues to be dried 5-30 minutes, makes micropill moisture<1.5%, bag isolation is obtained
The naproxen enteric-coated micro-pill of layer II；
(10) esomeprazole magnesium medicine-feeding suspension is configured：By esomeprazole magnesium, adhesive (25%-45% of total amount)
Add in 70%-80% ethanol with pH adjusting agent, esomeprazole magnesium medicine-feeding suspension is made in persistently stirring；
(11) the naproxen enteric-coated micro-pill of step (9) bag separation layer II is put in fluid bed, is preheated to product temperature for 35
DEG C -45 DEG C, spray into the esomeprazole magnesium medicine-feeding suspension of step (10), adjust fluid bed EAT (45 DEG C -70 DEG C),
(60m3/h-1000m3/ h), hydrojet speed (2g/min-250g/min) and atomizing pressure (1bar-3bar), make micropill in stream
Change state, adhesion, is not spray-dried, until medicine-feeding suspension has sprayed, continues to be dried 5-30 minutes, makes micropill moisture<
1.5%, obtain naproxen and the compound enteric-coated micropill of esomeprazole magnesium；
(12) color layers coating solution is configured：Remaining adhesive, titanium dioxide and iron oxide yellow are added into 70%-80% second
In alcohol, 60 mesh sieves are crossed after persistently stirring, make color layers suspension；
(13) the compound enteric-coated micropill of naproxen esomeprazole magnesium of step (11) is put in fluid bed, is preheated to product temperature
Spend for 35-45 DEG C, spray into step (12) color layers suspension, adjust fluid bed EAT (45-70 DEG C), intake volume (60-
1000m3/ h), hydrojet speed (2-250g/min) and atomizing pressure (1-3bar), make micropill in fluidized state, adhesion, no
It is spray-dried, until color layers suspension has sprayed, continues to be dried 5-30 minutes, makes micropill moisture<1.5%, obtain the Nabumetone of colouring
The raw and compound enteric-coated micropill of esomeprazole magnesium；
(14) naproxen of step (13) and the compound enteric-coated micropill of esomeprazole magnesium are picked up from into dynamic capsule filling machine filling
To in capsule shells, naproxen and the compound enteric-coated capsule of esomeprazole magnesium is obtained.
Naproxen of the present invention and the compound enteric-coated capsule Jing drug release determinations test of esomeprazole magnesium, as a result show naphthalene
Release ＞ 85% of general raw 60min, the release of esomeprazole magnesium 45min>80%, reach release 85%-95%.
The compound enteric-coated capsule of naproxen esomeprazole magnesium of the present invention put under acceleration environment (40 DEG C of temperature, relatively
Humidity 75 ± 5%) is placed 3 months, and the result with 0 month is compared, the proterties of its content, release, content and relevant thing
Matter has no significant change, and esomeprazole magnesium uniformity of dosage units is qualified, steady quality.
Instant invention overcomes the defect of prior art, has reached preferable effect：
(1) added medicine to using esomeprazole magnesium coating of pellets, the impact of the defect of single micropill to drug effect fruit on the whole compared with
It is little, compared to the tablet of single unit medicine-feeding efficiency more easy to control, so as to the stable content and content that ensure esomeprazole magnesium are equal
Evenness is qualified.
(2) when naproxen pastille micropill outsourcing separation layer can avoid enteric coated, naproxen enters into enteric coating layer and shadow
Ring release and stability.
(3) enteric layer and esomeprazole magnesium medicine accommodation layer are separated with separation layer, the enteric bag of acidity can be effectively prevented from
Clothing liquid produces impact to the stability of esomeprazole magnesium.
(4) alkaline conditioner is added in esomeprazole magnesium medicine-feeding coating solution, can partly avoids esomeprazole magnesium
Degrade in medicine-feeding and placement process.
(5) present invention is less than the individual difference of the tablet of single unit for multiunit pellet preparations, and can avoid local
Drug concentration is too high, and excitant is little.
(6) using HPMC capsule shells, compared to gelatine capsule shell (water content of 13%-16%), HPMC softgel shells have aqueous
Amount is low, and water vapour transit dose is low, the hardly friability and the advantages of good high temperatures in low-humidity environment.Therefore, it can
The moisture in esomeprazole magnesium ingress of air and in softgel shell is reduced, drug degradation is reduced, stability and shelf life is improved；And
In drier used in HPDE bottles, it is not result in that softgel shell is hardened embrittlement.
Supplementary material used of the invention is easy to get, and preparation process is simple is controllable, is suitable for large-scale industrial production, there is higher
Using value.
Specific embodiment
Supplementary material used by following examples is and is commercially available.
Embodiment 1：Naproxen esomeprazole magnesium enteric coatel tablets
Preparation method：
(1) take Hydroxypropyl methylcellulose (E5) 375g and be dissolved under 6750g purified waters, stirring and be slowly added to adopt airslide disintegrating mill
(model H100) micronized Nabumetone raw feedstock 1875g (D90<10 microns), the medicine-feeding suspension of naproxen is made in persistently stirring；
(2) take sucrose capsule core (0.1-0.2mm) 480g to be placed in fluid bed (model FLZB-10), be preheated to product temperature
For 40 DEG C ± 2 DEG C, step (1) medicine-feeding suspension is sprayed into, adjust fluid bed EAT (55-65 DEG C), intake volume (300-
800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar) (wanting specific condition data, scope can not be set)
Product temperature is made for 40 ± 2 DEG C, and makes micropill in fluidized state, adhesion, be not spray-dried, until medicine-feeding suspension spray
It is complete, product temperature is maintained, continue to be dried 25 minutes, make micropill moisture<1.5%, obtain naproxen coated pellets；
(3) coating solution of separation layer I is prepared：102g Hydroxypropyl methylcelluloses (E5) are dissolved in 80% ethanol of 1706g, are stirred
The coating solution of separation layer I is made in lower addition 34g talcum powder, persistently stirring；
(4) step (2) naproxen coated pellets are put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (3) step
The coating solution of separation layer I, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, obtain the naproxen coated pellets of bag separation layer I；
(5) enteric coating liquid is prepared：500g purified waters are taken, 70 DEG C are heated to, 16g triethyl citrates and 3g tweens is added
80, disperseed with dispersion machine (model T18), add glycerin monostearate 10g, dispersion machine to disperse 20 minutes, add 572g purifying
Water, is persistently stirred with mixer, is cooled to 30 DEG C, then is mixed with Utech L30D-55 of 1910g, low rate mixing, and enteric is obtained
Coating solution；
(6) naproxen coated pellets of step (4) bag separation layer I are put in fluid bed, are preheated to product temperature for 25-30 DEG C,
Step (5) enteric coating liquid is sprayed into, fluid bed EAT (35-45 DEG C), intake volume (300-800m is adjusted3/ h), hydrojet
Speed (5-100g/min) and atomizing pressure (1-3bar), make product temperature for 25-35 DEG C, and make micropill in fluidized state,
Adhesion, it is not spray-dried, until enteric coating liquid has been sprayed, maintains product temperature, continue to be dried 25 minutes, makes micropill moisture<
1.5%, obtain naproxen enteric-coated micro-pill；
(7) coating solution of separation layer II is prepared：130g Hydroxypropyl methylcelluloses (E5) are dissolved in 80% ethanol of 2168g, are stirred
Lower addition 43g talcum powder is mixed, the coating solution of separation layer II is made in persistently stirring；
(8) step (6) naproxen enteric layer micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into
(7) coating solution of step separation layer II, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed
Degree (5-100g/min) and atomizing pressure (1-3bar), make product temperature for 37 ± 2 DEG C, and make micropill be in fluidized state, no
Adhesion, it is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill
Moisture<1.5%, the naproxen enteric-coated micro-pill of bag separation layer II is obtained；
(9) Hydroxypropyl methylcellulose (E5) 307g is dissolved in 80% ethanol of 3070g, is slowly added to successively under stirring anhydrous
Esomeprazole magnesium is made in sodium carbonate 30g and esomeprazole magnesium raw material 100g (in terms of esomeprazole magnesium), persistently stirring
Medicine-feeding suspension；
(10) the naproxen enteric-coated micro-pill of the bag separation layer II of step (8) is placed in fluid bed (model FLZB-10), in advance
Heat to product temperature is 40 DEG C ± 2 DEG C, sprays into the medicine-feeding suspension of the esomeprazole magnesium of step (9), adjusts fluid bed air intake
Temperature (55-65 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar), make
Product temperature is 40 ± 2 DEG C, and makes micropill in fluidized state, adhesion, is not spray-dried, until medicine-feeding suspension has sprayed,
Product temperature is maintained, continues to be dried 25 minutes, make micropill moisture<1.5%, obtain naproxen and esomeprazole magnesium compound micropill；
(11) color clothing layer coating solution is prepared：153g Hydroxypropyl methylcelluloses (E5) are dissolved in 80% ethanol of 2549g, are stirred
The titanium dioxide and the iron oxide yellow of 25g of lower addition 25g are mixed, 60 mesh sieves are crossed after persistently stirring, make color clothing layer coating solution；
(12) step (10) naproxen and esomeprazole magnesium compound micropill are put in fluid bed, being preheated to product temperature is
37 DEG C ± 2 DEG C, the coating solution of (3) step separation layer 1 is sprayed into, adjust fluid bed EAT (47-57 DEG C), intake volume (300-
800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar), make product temperature for 37 ± 2 DEG C, and make micropill
In fluidized state, adhesion, it is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continues dry
Dry 15 minutes, make micropill moisture<1.5%, obtain the compound enteric-coated micropill of naproxen esomeprazole magnesium, per weight 428.3mg.
(13) the compound enteric-coated micropill of naproxen esomeprazole magnesium of step (12) is filled using INCAP XL automatic capsules
In being loaded into No. 00 gelatine capsule shell.
Embodiment 2：Naproxen esomeprazole magnesium capsulae enterosolubilis
Preparation method：
(1) take Hydroxypropyl methylcellulose (E5) 500g and be dissolved under 9000g purified waters, stirring and be slowly added to adopt airslide disintegrating mill
(model H100) micronized Nabumetone raw feedstock 2500g (D90<10 microns), the medicine-feeding suspension of naproxen is made in persistently stirring；
(2) take sucrose capsule core (0.1-0.2mm) 640g to be placed in fluid bed (model FLZB-10), be preheated to product temperature
For 40 DEG C ± 2 DEG C, step (1) medicine-feeding suspension is sprayed into, adjust fluid bed EAT (55-65 DEG C), intake volume (300-
800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar), make product temperature for 40 ± 2 DEG C, and make micropill
In fluidized state, adhesion, it is not spray-dried, until medicine-feeding suspension spray, maintains product temperature, continues 25 points of drying
Clock, makes micropill moisture<1.5%, obtain pastille micropill；
(3) coating solution of separation layer 1 is prepared：137g Hydroxypropyl methylcelluloses (E5) are dissolved in 80% ethanol of 2275g, are stirred
The coating solution of separation layer 1 is made in lower addition 45.5g talcum powder, persistently stirring；
(4) step (2) pastille micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (3) step every
The coating solution of absciss layer 1, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, obtain the micropill of separation layer 1；
(5) enteric coating liquid is prepared：700g purified waters are taken, 70 DEG C are heated to, 22g triethyl citrates and 4g tweens is added
80, disperseed with dispersion machine (model T18), add glycerin monostearate 13g, dispersion machine to disperse 20 minutes, add 729g purifying
Water, is persistently stirred with mixer, is cooled to 30 DEG C, then is mixed with Utech L30D-55, low rate mixing, and enteric coating liquid is obtained；
(6) micropill of step (4) separation layer 1 is put in fluid bed, is preheated to product temperature for 25-30 DEG C, spray into step (5)
Enteric coating liquid, adjusts fluid bed EAT (35-45 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-100g/
Min) and atomizing pressure (1-3bar), product temperature is made for 25-30 DEG C, and make micropill in fluidized state, adhesion, do not spray
It is dried, until enteric coating liquid has been sprayed, maintains product temperature, continue to be dried 25 minutes, makes micropill moisture<1.5%, obtain enteric layer
Micropill；
(7) coating solution of separation layer 2 is prepared：173g Hydroxypropyl methylcelluloses (E5) are dissolved in 80% ethanol of 2890g, are stirred
The coating solution of separation layer 2 is made in lower addition 58g talcum powder, persistently stirring；
(8) step (6) enteric layer micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (7) step
The coating solution of separation layer 2, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 35 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, the naproxen enteric-coated micro-pill of bag separation layer 2 is obtained；
(9) Hydroxypropyl methylcellulose (E5) 453g is dissolved in 80% ethanol of 625g, is slowly added to successively under stirring anhydrous
Esomeprazole magnesium is made in sodium carbonate 30g and esomeprazole magnesium raw material 100g (in terms of esomeprazole magnesium), persistently stirring
Medicine-feeding suspension；
(10) the naproxen enteric-coated micro-pill of the bag separation layer 2 of step (8) is placed in fluid bed (model FLZB-10), in advance
Heat to product temperature is 40 DEG C ± 2 DEG C, sprays into the medicine-feeding suspension of the esomeprazole magnesium of step (9), adjusts fluid bed air intake
Temperature (55-65 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar), make
Product temperature is 40 ± 2 DEG C, and makes micropill in fluidized state, adhesion, is not spray-dried, until medicine-feeding suspension has sprayed,
Product temperature is maintained, continues to be dried 25 minutes, make micropill moisture<1.5%, obtain compound micropill；
(11) color clothing layer coating solution is prepared：204g Hydroxypropyl methylcelluloses (E5) are dissolved in 80% ethanol of 3399g, are stirred
The titanium dioxide and the iron oxide yellow of 34g of lower addition 34g are mixed, 60 mesh sieves are crossed after persistently stirring, make color clothing layer coating solution；
(12) step (10) compound micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (3) step
The coating solution of separation layer 1, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, obtain the compound enteric-coated micropill of naproxen esomeprazole magnesium, per weight 571mg.
(13) the compound enteric-coated micropill of naproxen esomeprazole magnesium of step (12) is filled using INCAP XL automatic capsules
In being loaded into No. 00 gelatine capsule shell.
Embodiment 3：Naproxen esomeprazole magnesium enteric coatel tablets
Preparation method：
(1) PVP K30 375g are taken it is dissolved under 6750g purified waters, stirring and is slowly added to using airslide disintegrating mill (model
H100) micronized Nabumetone raw feedstock 1875g (D90<10 microns), the medicine-feeding suspension of naproxen is made in persistently stirring；
(2) take microcrystalline cellulose capsule core (0.1-0.2mm) 510g to be placed in fluid bed (model FLZB-10), be preheated to product
Product temperature degree is 40 DEG C ± 2 DEG C, sprays into step (1) medicine-feeding suspension, adjusts fluid bed EAT (55-65 DEG C), intake volume
(300-800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar), make product temperature for 40 ± 2 DEG C, and make
Micropill is in fluidized state, adhesion, is not spray-dried, until medicine-feeding suspension spray, maintains product temperature, continues dry 25
Minute, make micropill moisture<1.5%, obtain pastille micropill；
(3) coating solution of separation layer 1 is prepared：92g PVP K30 are dissolved in 70% ethanol of 1587g, stirring is lower to add 46g
The coating solution of separation layer 1 is made in talcum powder, persistently stirring；
(4) step (2) pastille micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (3) step every
The coating solution of absciss layer 1, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, obtain the micropill of separation layer 1；
(5) enteric coating liquid is prepared：500g purified waters are taken, 70 DEG C are heated to, 15g triethyl citrates and 3g tweens is added
80, disperseed with dispersion machine (model T18), add glycerin monostearate 10g, dispersion machine to disperse 20 minutes, add 531g purifying
Water, is persistently stirred with mixer, is cooled to 30 DEG C, then is mixed with Utech L30D-55 of 1839g, low rate mixing, and enteric is obtained
Coating solution；
(6) micropill of step (4) separation layer 1 is put in fluid bed, is preheated to product temperature for 25-30 DEG C, spray into step (5)
Enteric coating liquid, adjusts fluid bed EAT (35-45 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-100g/
Min) and atomizing pressure (1-3bar), product temperature is made for 25-35 DEG C, and make micropill in fluidized state, adhesion, do not spray
It is dried, until enteric coating liquid has been sprayed, maintains product temperature, continue to be dried 25 minutes, makes micropill moisture<1.5%, obtain enteric layer
Micropill；
(7) coating solution of separation layer 2 is prepared：116g PVP K30 are dissolved in 70% ethanol of 2000g, stirring is lower to be added
The coating solution of separation layer 2 is made in 58g talcum powder, persistently stirring；
(8) step (6) enteric layer micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (7) step
The coating solution of separation layer 2, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, the naproxen enteric-coated micro-pill of bag separation layer 2 is obtained；
(9) PVP K30 371g are dissolved in 70% ethanol of 4600g, be slowly added to successively under stirring magnesia 40g and
The medicine-feeding suspension of esomeprazole magnesium is made in esomeprazole magnesium raw material 100g (in terms of esomeprazole magnesium), persistently stirring；
(10) the naproxen enteric-coated micro-pill of the bag separation layer 2 of step (8) is placed in fluid bed (model FLZB-10), in advance
Heat to product temperature is 40 DEG C ± 2 DEG C, sprays into the medicine-feeding suspension of the esomeprazole magnesium of step (9), adjusts fluid bed air intake
Temperature (55-65 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar), make
Product temperature is 40 ± 2 DEG C, and makes micropill in fluidized state, adhesion, is not spray-dried, until medicine-feeding suspension has sprayed,
Product temperature is maintained, continues to be dried 25 minutes, make micropill moisture<1.5%, obtain compound micropill；
(11) color clothing layer coating solution is prepared：139g PVP K30 are dissolved in 70% ethanol of 2393g, stirring is lower to be added
The titanium dioxide of 35g and the iron oxide yellow of 35g, cross 60 mesh sieves after persistently stirring, make color clothing layer coating solution；
(12) step (10) compound micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (3) step
The coating solution of separation layer 1, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, obtain the compound enteric-coated micropill of naproxen esomeprazole magnesium, per weight 437.1mg.
(13) the compound enteric-coated micropill of naproxen esomeprazole magnesium of step (12) is filled using INCAP XL automatic capsules
In being loaded into No. 00 gelatine capsule shell.
Embodiment 4：Naproxen esomeprazole magnesium capsulae enterosolubilis
Preparation method：
(1) PVP K30 500g are taken it is dissolved under 9000g purified waters, stirring and is slowly added to using airslide disintegrating mill (model
H100) micronized Nabumetone raw feedstock 2500g (D90<10 microns), the medicine-feeding suspension of naproxen is made in persistently stirring；
(2) take microcrystalline cellulose capsule core (0.1-0.2mm) 510g to be placed in fluid bed (model FLZB-10), be preheated to product
Product temperature degree is 40 DEG C ± 2 DEG C, sprays into step (1) medicine-feeding suspension, adjusts fluid bed EAT (55-65 DEG C), intake volume
(300-800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar), make product temperature for 40 ± 2 DEG C, and make
Micropill is in fluidized state, adhesion, is not spray-dried, until medicine-feeding suspension spray, maintains product temperature, continues dry 25
Minute, make micropill moisture<1.5%, obtain pastille micropill；
(3) coating solution of separation layer 1 is prepared：123g PVP K30 are dissolved in 70% ethanol of 2116g, stirring is lower to be added
The coating solution of separation layer 1 is made in 61g talcum powder, persistently stirring；
(4) step (2) pastille micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (3) step every
The coating solution of absciss layer 1, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, obtain the micropill of separation layer 1；
(5) enteric coating liquid is prepared：600g purified waters are taken, 70 DEG C are heated to, 21g triethyl citrates and 4g tweens is added
80, disperseed with dispersion machine (model T18), add glycerin monostearate 13g, dispersion machine to disperse 20 minutes, add 775g purifying
Water, is persistently stirred with mixer, is cooled to 30 DEG C, then is mixed with Utech L30D-55 of 2452g, low rate mixing, and enteric is obtained
Coating solution；
(6) micropill of step (4) separation layer 1 is put in fluid bed, is preheated to product temperature for 25-30 DEG C, spray into step (5)
Enteric coating liquid, adjusts fluid bed EAT (35-45 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-100g/
Min) and atomizing pressure (1-3bar), product temperature is made for 25-35 DEG C, and make micropill in fluidized state, adhesion, do not spray
It is dried, until enteric coating liquid has been sprayed, maintains product temperature, continue to be dried 25 minutes, makes micropill moisture<1.5%, obtain enteric layer
Micropill；
(7) coating solution of separation layer 2 is prepared：155g PVP K30 are dissolved in 70% ethanol of 2666g, stirring is lower to be added
The coating solution of separation layer 2 is made in 77g talcum powder, persistently stirring；
(8) step (6) enteric layer micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (7) step
The coating solution of separation layer 2, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, the naproxen enteric-coated micro-pill of bag separation layer 2 is obtained；
(9) PVP K30 444g are dissolved in 70% ethanol of 5258g, be slowly added to successively under stirring magnesia 40g and
The medicine-feeding suspension of esomeprazole magnesium is made in esomeprazole magnesium raw material 100g (in terms of esomeprazole magnesium), persistently stirring；
(10) the naproxen enteric-coated micro-pill of the bag separation layer 2 of step (8) is placed in fluid bed (model FLZB-10), in advance
Heat to product temperature is 40 DEG C ± 2 DEG C, sprays into the medicine-feeding suspension of the esomeprazole magnesium of step (9), adjusts fluid bed air intake
Temperature (55-65 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-100g/min) and atomizing pressure (1-3bar), make
Product temperature is 40 ± 2 DEG C, and makes micropill in fluidized state, adhesion, is not spray-dried, until medicine-feeding suspension has sprayed,
Product temperature is maintained, continues to be dried 25 minutes, make micropill moisture<1.5%, obtain compound micropill；
(11) color clothing layer coating solution is prepared：182g PVP K30 are dissolved in 70% ethanol of 3135g, stirring is lower to be added
The titanium dioxide of 45g and the iron oxide yellow of 45g, cross 60 mesh sieves after persistently stirring, make color clothing layer coating solution；
(12) step (10) compound micropill is put in fluid bed, is preheated to product temperature for 37 DEG C ± 2 DEG C, spray into (3) step
The coating solution of separation layer 1, adjusts fluid bed EAT (47-57 DEG C), intake volume (300-800m3/ h), hydrojet speed (5-
100g/min) and atomizing pressure (1-3bar), product temperature is made for 37 ± 2 DEG C, and make micropill in fluidized state, adhesion,
It is not spray-dried, until separation layer solution or suspension have sprayed, maintains product temperature, continue to be dried 15 minutes, makes micropill moisture<
1.5%, obtain the compound enteric-coated micropill of naproxen esomeprazole magnesium, per weight 572.6mg.
(13) the compound enteric-coated micropill of naproxen esomeprazole magnesium of step (12) is filled using INCAP XL automatic capsules
In being loaded into No. 00 gelatine capsule shell.
Embodiment 5：The compound enteric-coated micropill of naproxen esomeprazole magnesium of the present invention be filled in HPMC softgel shells (
Plus in).
With reference to the formula and technique of embodiment 2, the compound enteric-coated micropill of naproxen esomeprazole magnesium is prepared, micropill is adopted
INCAP XL automatic capsule bottle placers are loaded into No. 00 HPMC softgel shell.
Embodiment 6：The release of the compound enteric-coated capsule (embodiment 1,2,3,4) of naproxen esomeprazole magnesium of the present invention
Degree is determined.
ReferenceFDA releases clearance condition, it is Example 1, embodiment 2, embodiment 3, embodiment 4, real
Capsule obtained in example 5, plus sedimentation basket are applied, is carried out according to two method of annex dissolution methods second (slurry processes) of Chinese Pharmacopoeia 2015 edition
Determine.
Burst size in the acid of naproxen：With 0.1M hydrochloric acid solution 1000ml as dissolution medium, rotating speed is 50rpm, is grasped in accordance with the law
Make, Jing 2 hours, take out capsule and sedimentation basket, in remaining acid medium 10M sodium hydroxide solution 10ml are added, continue to stir
30min, rotating speed 100rpm, are measured by sampling naproxen content, calculate burst size in naproxen acid, and limit is less than 10%.
Naproxen burst size in cushioning liquid：The capsule of above-mentioned taking-up and sedimentation basket, are transferred to containing 1000ml0.05M
In the stripping rotor of pH6.8 phosphate buffers, rotating speed is 50rpm, is operated in accordance with the law, during Jing 60 minutes, is measured by sampling and calculates and release
High-volume, its limit should be not less than 85%.
Burst size of the esomeprazole magnesium in cushioning liquid：With 0.05M pH7.4 phosphate buffer 900ml as dissolution
Medium, rotating speed is 75rpm, is operated in accordance with the law, during Jing 45 minutes, is measured by sampling and calculates burst size, and its limit should be not less than 80%.
Table 1
The result of above-mentioned dissolution test shows：Naproxen esomeprazole magnesium capsulae enterosolubilis of the present invention, its naphthalene
General life 2h burst size≤10% in acid, in 60 minutes burst size >=85% of pH6.8 phosphate buffers；Its esomeprazole magnesium
Medicine 45 minutes burst size >=80% in pH7.4 phosphate buffers, meet the requirement of quality standard.
Embodiment 7：Naproxen of the present invention and the compound enteric-coated capsule of esomeprazole magnesium (embodiment 1,2,5) are stablized
Property test.
Respectively Example 1, embodiment 2, the capsule of embodiment 5, are packed using solid medicinal high-density polyethylene bottle
(interior plus 1g drier), in 40 DEG C of temperature, places 3 months in the climatic chamber of relative humidity 75 ± 5%, respectively at 0,1, March
It is measured by sampling, the results are shown in Table 2, table 3.
Table 2
Table 3
The result of aforementioned stable test shows：Naproxen esomeprazole magnesium capsulae enterosolubilis of the present invention is accelerating
Under the conditions of (40 DEG C of temperature, after relative humidity 75 ± 5%) is placed 3 months, the result with 0 month is compared, the property of its content
Shape, release, content are qualified and without significant change, wherein substantially unchanged using the relevant material of HPMC softgel shells, Esso is beautiful to be drawn
Azoles magnesium steady quality, and be increased slightly using the impurity of gelatine capsule shell.
Claims (10)
1. naproxen and the compound enteric-coated capsule of esomeprazole magnesium, it is characterised in that the naproxen and esomeprazole magnesium are multiple
The content of square capsulae enterosolubilis is the compound by made by the naproxen and esomeprazole magnesium as active component and pharmaceutic adjuvant
Enteric-coated micro-pill.
2. naproxen and the compound enteric-coated capsule of esomeprazole magnesium according to claim 1, it is characterised in that the compound intestines
The structure of molten micropill be followed successively by from inside to outside blank capsule core, naproxen medicated layer, separation layer I, enteric coating layer, separation layer II, angstrom
Suo Meila azoles magnesium medicated layers and color clothing layer.
3. naproxen and the compound enteric-coated capsule of esomeprazole magnesium according to claim 1, it is characterised in that
The described compound enteric-coated capsule of naproxen and esomeprazole magnesium, per 187.5mg-250mg containing naproxen is beautiful containing Esso
Draw azoles magnesium 10mg in terms of esomeprazole.
4. naproxen and the compound enteric-coated capsule of esomeprazole magnesium according to claim 1, it is characterised in that described Nabumetone
The raw and compound enteric-coated micropill of esomeprazole magnesium is by following weight proportion into being grouped into：In terms of 1000
(1) the compound enteric-coated micropill of naproxen esomeprazole magnesium:
5. naproxen and the compound enteric-coated capsule of esomeprazole magnesium according to claim 1, it is characterised in that described Nabumetone
The raw and compound enteric-coated micropill of esomeprazole magnesium is by following weight proportion into being grouped into：In terms of 1000
6. naproxen and the compound enteric-coated capsule of esomeprazole magnesium according to claim 1, it is characterised in that the blank pill
The particle diameter of core is 0.1mm-0.2mm；Selected from sucrose capsule core, microcrystalline cellulose capsule core or silica capsule core, preferably sucrose capsule core；
Described adhesive is selected from one or more in Hydroxypropyl methylcellulose, PVP or hydroxypropyl cellulose, preferred hypromellose
Plain E5；The pH adjusting agent is selected from sodium carbonate, sodium acid carbonate, NaOH or magnesia, preferred sodium carbonate.
7. naproxen and the compound enteric-coated capsule of esomeprazole magnesium according to claim 6, it is characterised in that the blank pill
Core is sucrose capsule core；Described adhesive is Hydroxypropyl methylcellulose E5；The pH adjusting agent is sodium carbonate.
8. naproxen and the compound enteric-coated capsule of esomeprazole magnesium according to claim 1, it is characterised in that the capsule
Softgel shell is selected from gelatin softgel shell or HPMC softgel shells, preferred HPMC softgel shells.
9. naproxen and the compound enteric-coated capsule of esomeprazole magnesium according to claim 8, it is characterised in that the capsule
Softgel shell is HPMC softgel shells.
10. the method for preparing naproxen and the compound enteric-coated capsule of esomeprazole magnesium described in any one of claim 1-5, its feature
It is that the method is comprised the following steps：
(1) naproxen is adopted into airslide disintegrating mill micronizing D90<It is 10 microns, standby；
(2) 25%-45% of adhesive total amount is dissolved under purified water, stirring and is slowly added to step (1) material, persistently stirring system
Into naproxen medicine-feeding suspension；
(3) blank capsule core is put in fluid bed, is preheated to product temperature for 35 DEG C -45 DEG C, spray into the medicine-feeding of step (2) naproxen mixed
Suspension, adjusts fluid bed EAT, intake volume, hydrojet speed and atomizing pressure, makes micropill in fluidized state, does not glue
Even, it is not spray-dried, until medicine-feeding suspension has sprayed, continues to be dried 5-30 minutes, makes micropill moisture<1.5%, obtain naproxen micro-
Ball；
(4) coating solution of configuration isolation layer I：The 30%-60% of the 5%-20% of adhesive total amount and antiplastering aid total amount is added
In the ethanol of 70%-80%, the coating solution of separation layer I is made in persistently stirring；
(5) the naproxen pastille micropill of step (3) is put in fluid bed, is preheated to product temperature for 35 DEG C -45 DEG C, spray into step
(4) coating solution of separation layer I, adjusts 45 DEG C -70 DEG C of fluid bed EAT, intake volume 60m3/h-1000m3/ h, hydrojet speed
2g/min-250g/min and atomizing pressure 1bar-3bar, makes micropill in fluidized state, adhesion, is not spray-dried, until
Separation layer solution or suspension have sprayed, and continue to be dried 5-30 minutes, make micropill moisture<1.5%, obtain the naproxen of bag separation layer I
Micropill；
(6) enteric layer coating solution is configured：The 40%-60% of suitable quantity of water enteric coating liquid plus water inventory is taken, 70 DEG C are heated to, is added
Triethyl citrate and Tween 80, are disperseed with dispersion machine, add glycerin monostearate, dispersion machine dispersion 10-30 minutes, are added
Remaining water, is persistently stirred with mixer, is cooled to 10 DEG C -40 DEG C, then is mixed with Utech L30D-55, and low rate mixing obtains enteric
Coating solution；
(7) naproxen coated pellets of the bag separation layer I of step (5) are put in fluid bed, are preheated to product temperature for 25 DEG C -35 DEG C,
Step (6) enteric coating liquid is sprayed into, 35 DEG C -70 DEG C of fluid bed EAT, intake volume 60m is adjusted3/h-1000m3/ h, hydrojet
Speed 2g/min-250g/min and atomizing pressure 1bar-3bar, make micropill in fluidized state, adhesion, are not spray-dried,
Until coating solution has sprayed, continue to be dried 5-30 minutes, make micropill moisture<1.5%, obtain naproxen enteric-coated micro-pill；
(8) coating solution of configuration isolation layer II：Adhesive (5%-20% of total amount) and antiplastering aid (50%-70% of total amount) is molten
In the ethanol of 70%-80%, the coating solution of separation layer II is made in persistently stirring；
(9) step (7) naproxen enteric-coated micro-pill is put in fluid bed, is preheated to product temperature for 35 DEG C -45 DEG C, spray into step
(8) coating solution of separation layer II, adjusts 45 DEG C -70 DEG C of fluid bed EAT, intake volume 60m3/h-1000m3/ h, hydrojet speed
2g/min-250g/min and atomizing pressure 1bar-3bar, makes micropill in fluidized state, adhesion, is not spray-dried, until
Separation layer solution or suspension have sprayed, and continue to be dried 5-30 minutes, make micropill moisture<1.5%, the Nabumetone of bag separation layer II is obtained
Raw enteric-coated micro-pill；
(10) esomeprazole magnesium medicine-feeding suspension is configured：Esomeprazole magnesium, the 25%-45% of adhesive total amount and pH are adjusted
Section agent is added in 70%-80% ethanol, and esomeprazole magnesium medicine-feeding suspension is made in persistently stirring；
(11) the naproxen enteric-coated micro-pill of step (9) bag separation layer II is put in fluid bed, is preheated to product temperature for 35 DEG C -45
DEG C, the esomeprazole magnesium medicine-feeding suspension of step (10) is sprayed into, adjust 45 DEG C -70 DEG C of fluid bed EAT, 60m3/h-
1000m3/ h, hydrojet speed 2g/min-250g/min and atomizing pressure 1bar-3bar, make micropill in fluidized state, do not glue
Even, it is not spray-dried, until medicine-feeding suspension has sprayed, continues to be dried 5-30 minutes, makes micropill moisture<1.5%, obtain naproxen and
The compound enteric-coated micropill of esomeprazole magnesium；
(12) color layers coating solution is configured：Remaining adhesive, titanium dioxide and iron oxide yellow are added into 70%-80% ethanol
In, 60 mesh sieves are crossed after persistently stirring, make color layers suspension；
(13) the compound enteric-coated micropill of naproxen esomeprazole magnesium of step (11) is put in fluid bed, being preheated to product temperature is
35-45 DEG C, step (12) color layers suspension is sprayed into, adjust 45-70 DEG C of fluid bed EAT, intake volume 60-1000m3/
H, hydrojet speed 2-250g/min and atomizing pressure 1-3bar, make micropill in fluidized state, adhesion, are not spray-dried, directly
Spray to color layers suspension, continued to be dried 5-30 minutes, made micropill moisture<1.5%, obtain the U.S. drawing of naproxen and Esso of colouring
The compound enteric-coated micropill of azoles magnesium；
(14) naproxen of step (13) and the compound enteric-coated micropill of esomeprazole magnesium are picked up from into dynamic capsule filling machine and is loaded into glue
In softgel shell, naproxen and the compound enteric-coated capsule of esomeprazole magnesium is obtained.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510762517.9A CN106668017A (en) | 2015-11-11 | 2015-11-11 | Naproxen and esomeprazole magnesium compound enteric-coated capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510762517.9A CN106668017A (en) | 2015-11-11 | 2015-11-11 | Naproxen and esomeprazole magnesium compound enteric-coated capsule and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106668017A true CN106668017A (en) | 2017-05-17 |
Family
ID=58864806
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510762517.9A Pending CN106668017A (en) | 2015-11-11 | 2015-11-11 | Naproxen and esomeprazole magnesium compound enteric-coated capsule and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106668017A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116808001A (en) * | 2023-05-04 | 2023-09-29 | 上海信谊万象药业股份有限公司 | Dopa hydrazine enteric pellet capsule and preparation process thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1183048A (en) * | 1996-01-08 | 1998-05-27 | 阿斯特拉公司 | Oral pharmaceutical dosage forms comprising a proton pump inhibitor and nsaid |
| US20100305163A1 (en) * | 2009-05-20 | 2010-12-02 | Pramod Dattatray Yedurkar | Pharmaceutical formulations comprising nsaid and proton pump inhibitor drugs |
| CN104208039A (en) * | 2014-08-26 | 2014-12-17 | 杭州新诺华医药有限公司 | Naproxen esomeprazole enteric preparation and preparation method thereof |
-
2015
- 2015-11-11 CN CN201510762517.9A patent/CN106668017A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1183048A (en) * | 1996-01-08 | 1998-05-27 | 阿斯特拉公司 | Oral pharmaceutical dosage forms comprising a proton pump inhibitor and nsaid |
| US20100305163A1 (en) * | 2009-05-20 | 2010-12-02 | Pramod Dattatray Yedurkar | Pharmaceutical formulations comprising nsaid and proton pump inhibitor drugs |
| CN104208039A (en) * | 2014-08-26 | 2014-12-17 | 杭州新诺华医药有限公司 | Naproxen esomeprazole enteric preparation and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 沙露平 等: "复方萘普生钠肠溶-埃索美拉唑镁速释微丸型胶囊剂的研制", 《中国药剂学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116808001A (en) * | 2023-05-04 | 2023-09-29 | 上海信谊万象药业股份有限公司 | Dopa hydrazine enteric pellet capsule and preparation process thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104922086B (en) | A kind of preparation method of proton pump inhibitor enteric coatel tablets | |
| JP3665334B2 (en) | New pharmaceutical formulation | |
| CN104688691A (en) | Novel compositions based on gamma-hydroxybutyric acid | |
| CS244909B2 (en) | Production method of retarded form of bromohexine | |
| CN103260607A (en) | Process for the preparation of a PPI-containing pharmaceutical product | |
| CN101502491B (en) | Dirithromycin enteric-coated formulation | |
| CN100425235C (en) | Enteric omeprazole micropill and its preparing method | |
| CN103356489B (en) | Proton pump inhibitor enteric coated pellet and preparation and preparation method thereof | |
| CN105125517A (en) | Esomeprazole magnesium enteric pellet capsule and preparation method thereof | |
| CN101371836A (en) | Paroxetine enteric sustained-release composition | |
| CN102552256A (en) | Ilaprazole enteric capsule and preparation method thereof | |
| CN104208039B (en) | Naproxen esomeprazole enteric preparation and preparation method thereof | |
| CN104873473A (en) | Potassium chloride sustained-release tablet and preparation method thereof | |
| CN102626396A (en) | Metoprolol slow-release tablet and preparation method thereof | |
| WO2016088816A1 (en) | Tablet comprising zinc acetate hydrate and method for manufacturing same | |
| CA2517120C (en) | Pharmaceutical composition containing platinum complex as active substance and method of manufacturing thereof | |
| CN106668017A (en) | Naproxen and esomeprazole magnesium compound enteric-coated capsule and preparation method thereof | |
| CN102552190A (en) | Ilaprazole enteric coated tablet and preparation method thereof | |
| CN105434398B (en) | A kind of Rabeprazole enteric-coated micro-pill and preparation method thereof | |
| CN1321642C (en) | Enteric-coated pantoprazole sodium minipill | |
| CN103054835A (en) | Venlafaxine sustained-release capsule and preparation process thereof | |
| CN103006610B (en) | Esomeprazole sodium enteric-coated tablet and preparation method thereof | |
| CN114748443B (en) | Memantine hydrochloride sustained-release pellets and preparation method thereof | |
| CN105816436B (en) | A kind of Pantoprazole enteric-coated micro-pill, Pantoprazole enteric slow-release tablet agent and preparation method thereof | |
| CN106606496A (en) | Naproxen and esomeprazole magnesium compound enteric coated tablets and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 201210 Zhang Heng Road, 1999, China (Shanghai) free trade test area, Shanghai City, 7 Applicant after: Shanghai Double Star Thai Pharmaceutical Technology Co., Ltd. Address before: 201203 Shanghai city Pudong New Area Bing Road No. 306 building 3 floor No. 1 Applicant before: SHANGHAI SUNTECH PHARMACEUTICAL CO., LTD. |
|
| CB02 | Change of applicant information | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170517 |
|
| WD01 | Invention patent application deemed withdrawn after publication |