CN102552190A - Ilaprazole enteric coated tablet and preparation method thereof - Google Patents
Ilaprazole enteric coated tablet and preparation method thereof Download PDFInfo
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Abstract
The invention provides an ilaprazole enteric coated tablet and a preparation method thereof. The ilaprazole enteric coated tablet comprises enteric coated pellets and a pharmaceutically-acceptable tablet auxiliary material, wherein each enteric coated pellet comprises a pellet core, an isolating layer and an enteric coated layer; and the pellet core comprises ilaprazole or a pharmaceutically-acceptable salt thereof and a stabilizing agent. The enteric coated pellet tablet made from ilaprazole has high acid resistance; in a prescription, barrier substances such as an acid resisting agent, a surfactant, an organic solvent, a hydrophobic substance and the like are not contained, so that the health and safety of a human body are better facilitated; in the preparation method, an organic solvent is not used, so that operation is easy, and active substances are released quickly and stably; and moreover, the pellets in the tablet can be widely and uniformly distributed into an intestinal tract after administration, a dosage is poured out in a scatter way, and the distribution area of a medicament on the surface of the intestinal tract is increased, so that the stimulation of the medicament on the intestinal tract can be reduced or eliminated, and the bioavailability of the medicament is enhanced.
Description
Technical field
The present invention relates to a kind of enteric coated tablet that comprises proton pump inhibitor and preparation method thereof, be specifically related to a kind of enteric coated tablet that comprises ilaprazole or its pharmaceutically acceptable salt and preparation method thereof.
Background technology
Ilaprazole (Ilaprazole) is the latest generation proton pump inhibitor of the development of Korea S one foreign Pharmaceutical Co., Ltd, beautiful pearl medicine company limited exploitation listing; Be widely used for the digestive tract disease relevant, like duodenal ulcer, gastric ulcer, reflux esophagitis etc. with various acid.Compare with other PPI, ilaprazole has that antiacid activity is the strongest, the no individual variation of treatment, night are controlled advantages such as sour ability is stronger, is expected to become core product in the PPI market.
Ilaprazole is less stable in acid and neutral medium, in gastric acid, is prone to be destroyed, so domestic at present and international use clinically all is enteric coatel tablets.Enteric coated tablet is a single dose of drug, and the repeatability of its enteric effect is bad, causes easily that local concentration is too high to stimulate intestinal, and the drug release behavior that error or the defective of indivedual tablet products in preparation can cause whole preparation changes, and influences clinical efficacy.In addition, the stability of ilaprazole also receives the influence of light, humidity, heat, organic solvent (even trace).Therefore overcome the weakness of raw material itself through the formulation and technology technology, preparation good stability, the ilaprazole preparation that bioavailability is high seem most important.
Micropill is meant that diameter is about 1mm, generally is no more than the coccoid oral formulations of 2.5mm.Has lot of advantages after micropill further is pressed into tablet: after take (1); The micropill that disintegration of tablet obtains can be extensively, be evenly distributed in the gastrointestinal tract; Medicine increases at gastrointestinal surface distributed area, drug bioavailability is improved, and reduce or eliminate medicine to the gastrointestinal zest; (2) micropill absorbs the influence that a step does not receive gastric emptying at gastrointestinal, uniform absorption, and bioavailability among individuals difference is less; (3) drug release behavior of micropill is a summation of forming each piller drug release behavior of a dosage, and error or the defective unlikely drug release behavior generation to whole preparation of indivedual pillers in preparation has a strong impact on, and repeatability, the concordance of release rule are superior to tablet; (4) on the technology good fluidity is arranged, non-friable etc.
Summary of the invention
Therefore, the purpose of this invention is to provide a kind of enteric coated tablet that comprises ilaprazole or its pharmaceutically acceptable salt.Ilaprazole of the present invention is processed the enteric coated micropill tablet and is had good acid-resistant strength; Do not contain barrier materials such as antacid, surfactant, organic solvent and lyophobic dust in the prescription, more help health and safety; Method for preparing is not with an organic solvent, and is simple to operate, and outward appearance rounding homogeneous, active substance discharge stable rapidly; In addition since take in the tablet of back micropill can be extensively, be evenly distributed in the intestinal, dosage inclines and decentralizedly, medicine increases at intestinal surface distributed area, therefore can reduce or eliminate the zest of medicine to intestinal, the raising drug bioavailability.
Be used to realize that the technical scheme of above-mentioned purpose is following:
A kind of enteric coated tablet, this enteric coated tablet comprise enteric coated micropill and pharmaceutically acceptable additive of tablet, and said enteric coated micropill comprises micropellets, sealing coat and enteric coat layer, and said micropellets comprises ilaprazole or its pharmaceutically acceptable salt and stabilizing agent.
In above-mentioned enteric coated tablet, the pharmaceutically acceptable salt of ilaprazole can be ilaprazole sodium, ilaprazole magnesium, ilaprazole lithium, ilaprazole potassium, ilaprazole zinc and/or ilaprazole calcium.Structural formula is as shown in the formula shown in the 1-6:
Formula 1 ilaprazole is received
Formula 2 ilaprazole magnesium
Formula 3 ilaprazole potassium
Formula 4 ilaprazole lithiums
Formula 5 ilaprazole calcium
Formula 6 ilaprazole zinc
In above-mentioned enteric coated tablet; Stabilizing agent can be selected from one or more in magnesium oxide, magnesium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate and the aluminium hydroxide; The oxide of preferably magnesium is as stabilizing agent, i.e. magnesium oxide or magnesium hydroxide.Preferably, the ratio 0.5～5: 1 of stabilizing agent and the weight of ilaprazole or its pharmaceutically acceptable salt.
In above-mentioned enteric coated tablet, micropellets can comprise one or more substrate that are selected from oxide, cellulose, organic polymer, inorganic salt and sugar, and (wherein, oxide, cellulose, organic polymer are water-insoluble substrate; Inorganic salt and sugar are water-soluble base), and choose wantonly one or more be selected from the binding agent of hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose syrup (50-70% sucrose solution), starch, polyvinylpyrrolidone and sodium alginate; Preferably, the weight ratio of binding agent and substrate is 2～10: 98～90.The particle diameter of micropellets can be 0.1～2 millimeter, is preferably 0.2～1.3 millimeter.
In above-mentioned enteric coated tablet, sealing coat can comprise one or more binding agents that is selected from syrup (50-70% sucrose solution), Polyethylene Glycol, polyvinyl alcohol, polyvinyl acetate, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, methylcellulose, ethyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone and sodium alginate; One or more are selected from the stabilizing agent of magnesium oxide, magnesium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate and aluminium hydroxide; And optional plasticizer, for example one or more in triethyl citrate, Polyethylene Glycol, dimethyl phthalate, triacetyl glycerine and the dibutyl sebacate; Optional opacifier, for example titanium dioxide; Optional antiplastering aid, for example Pulvis Talci.Wherein, preferably, stabilizing agent is 5～50: 100 with the ratio of the weight of binding agent; The weight of binding agent can be 3～15% of micropellets weight.
In above-mentioned enteric coated tablet; Enteric coat layer can comprise one or more and be selected from cellulose families such as crylic acid resin, carboxylic first and second celluloses such as polyethylene kinds such as Lac, polyvinyl alcohol acetic acid phthalic acid ester, EUDRAGIT S100 (I number, II number, III number), the enteric-coating material of cellulose esters, Opadries etc. such as cellulose acetate phthalate ester, hypromellose phthalandione vinegar, hypromellose acetic acid succinate; And optional one or more are selected from the additive of plasticizer, antiplastering aid, lubricant and opacifier.The contained enteric coating material solid content of enteric coating increases weight to the 20-300% of micropellets, is preferably 50-150%.
In above-mentioned enteric coated tablet; Pharmaceutically acceptable additive of tablet can be selected from one or more in filler, binding agent, disintegrating agent and the lubricant, for example one or more in starch, sucrose, dextrin, lactose, pregelatinized Starch, microcrystalline Cellulose, inorganic salt, mannitol, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hydroxypropyl emthylcellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, magnesium stearate, micropowder silica gel and the Pulvis Talci.
The present invention also provides the method for preparing of above-mentioned enteric coated tablet, and this method may further comprise the steps:
(1) with above-mentioned enteric coated micropill and pharmaceutically acceptable additive of tablet directly mix, tabletting; Perhaps pharmaceutically acceptable additive of tablet is granulated, mix with above-mentioned enteric coated micropill again, tabletting;
(2) randomly, the tablet that step (1) is made coats film-coat or sugar-coat.
Wherein, in the tabletting process, the acid-resisting of the micropill that enteric coat layer coats is declined by less than 10%.
In above-mentioned method for preparing, the method for preparing of enteric coated micropill can may further comprise the steps:
(1) to extrude the micropellets that the spheronization preparation comprises ilaprazole or its pharmaceutically acceptable salt and stabilizing agent;
(2) on micropellets, coat sealing coat;
(3) on the micropellets that coats sealing coat, coat enteric coat layer.
Ilaprazole of the present invention is processed the enteric coated micropill tablet and is had good acid-resistant strength; Do not contain barrier materials such as antacid, surfactant, organic solvent and lyophobic dust in the prescription, more help health and safety; Method for preparing is not with an organic solvent, and is simple to operate, and active substance discharges stable rapidly; In addition since take in the tablet of back micropill can be extensively, be evenly distributed in the intestinal, dosage inclines and decentralizedly, medicine increases at intestinal surface distributed area, therefore can reduce or eliminate the zest of medicine to intestinal, the raising drug bioavailability.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is further described in detail, the embodiment that provides has been merely and has illustrated the present invention, rather than in order to limit scope of the present invention.
Embodiment 1: extrude the micropellets that the spheronization preparation contains ilaprazole sodium
Table 1 contains the micropellets prescription of ilaprazole sodium
| Material | Amount (g) |
| Microcrystalline Cellulose pH101 | 320 |
| Pregelatinized Starch | 80 |
| Ilaprazole sodium | 72 |
| Sodium hydroxide | 62 |
| Hydroxypropyl emthylcellulose 5cp | 10 |
| Water | 120 |
Take by weighing Mcc pH101 and pregelatinized Starch, mixed 60 mesh sieves; Take by weighing active component (being ilaprazole sodium) and sodium hydroxide, mixed 60 mesh sieves; With above-mentioned both mixing.Take by weighing hydroxypropyl emthylcellulose (HPMC) 5cp and use the small amount of thermal aqueous dispersion, add the water dissolution of prescription surplus again, slurrying (8% (m/m)).With said mixture material and slurry system soft material, and soft material is extruded round as a ball.Operating parameter is as shown in table 2, makes light yellow micropellets 539.5g, and yield is 99.2%.30 ℃ of following convection dryings or fluid bed drying.
Table 2 is extruded round as a ball operating parameter
| Parameter | Control |
| Extrude rotating speed (rpm) | 20-40 |
| Chilling temperature (℃) | 0-20 |
| Round as a ball rotating speed (rpm) | 1500-2000 |
| Blasting time (s) | 1-10 |
| Air blast time-delay (s) | 1-30 |
| Particle diameter mould (mm) | 0.3 |
Embodiment 2: extrude the micropellets that the spheronization preparation contains ilaprazole magnesium
Table 3 contains the micropellets prescription of ilaprazole magnesium
| Material | Amount (g) |
| Microcrystalline Cellulose pH101 | 320 |
| Starch | 90 |
| Ilaprazole magnesium | 72 |
| Magnesium hydroxide | 36 |
| Hydroxypropyl emthylcellulose 15cp | 6 |
| Water | 110 |
Take by weighing Mcc pH101 and starch, mixed 80 mesh sieves; Take by weighing active component (being ilaprazole magnesium) and magnesium hydroxide, mixed 80 mesh sieves; With above-mentioned both mixing.Take by weighing hydroxypropyl emthylcellulose (HPMC) 15cp and use the small amount of thermal aqueous dispersion, add the water dissolution of prescription surplus again, slurrying (5% (m/m)).With said mixture material and slurry system soft material, and soft material is extruded round as a ball.Major parameter is controlled to be: the particle diameter mould is 0.2mm, and extruding rotating speed is 20-30rpm, and round as a ball rotating speed is 2000-2500rpm.Make light yellow micropellets 522.4g, yield is 99.7%.30 ℃ of following convection dryings or fluid bed drying.
Embodiment 3: extrude the micropellets that the spheronization preparation contains the ilaprazole lithium
Table 4 contains the micropellets prescription of ilaprazole lithium
| Material | Amount (g) |
| Microcrystalline Cellulose pH101 | 250 |
| Lactose | 60 |
| The ilaprazole lithium | 72 |
| Sodium carbonate | 150 |
| 30 POVIDONE K 30 BP/USP 30 | 5 |
| 25% (v/v) ethanol water | 100 |
Take by weighing Mcc pH101 and lactose, mixed 100 mesh sieves; Take by weighing active component (being the ilaprazole lithium) and sodium carbonate, mixed 100 mesh sieves; With above-mentioned both mixing.Take by weighing 30 POVIDONE K 30 BP/USP 30, be dissolved among 25% (v/v) ethanol water 100g slurrying (5% (m/m)).With said mixture material and slurry system soft material, and soft material is extruded round as a ball.Major parameter is controlled to be: the particle diameter mould is 0.4mm, and extruding rotating speed is 20-40rpm, and round as a ball rotating speed is 1500-2500rpm.Make micropellets 535.8g, yield is 99.8%.30 ℃ of following convection dryings or fluid bed drying.
Embodiment 4: extrude the micropellets that the spheronization preparation contains ilaprazole potassium
Table 5 contains the micropellets prescription of ilaprazole potassium
| Material | Amount (g) |
| Pre-paying starch | 300 |
| Lactose | 60 |
| Ilaprazole potassium | 72 |
| Potassium hydroxide | 72 |
| 30 POVIDONE K 30 BP/USP 30 | 10 |
| 25% (v/v) ethanol water | 100 |
Take by weighing pregelatinized Starch and lactose, mixed 50 mesh sieves; Take by weighing active component (being ilaprazole potassium) and potassium hydroxide, mixed 100 mesh sieves; With above-mentioned both mixing.Take by weighing 30 POVIDONE K 30 BP/USP 30, be dissolved among 25% (v/v) ethanol water 100g slurrying (10% (m/m)).With said mixture material and slurry system soft material, and soft material is extruded round as a ball.Major parameter is controlled to be: the particle diameter mould is 0.4mm, and extruding rotating speed is 20-40rpm, and round as a ball rotating speed is 1500-2500rpm.Make micropellets 513.1g, yield is 99.8%.30 ℃ of following convection dryings or fluid bed drying.
Embodiment 5: extrude the micropellets that the spheronization preparation contains ilaprazole calcium
Table 6 contains the micropellets prescription of ilaprazole calcium
| Material | Amount (g) |
| Pre-paying starch | 300 |
| Mannitol | 60 |
| Ilaprazole calcium | 72 |
| Sodium bicarbonate | 30 |
| Sodium hydroxide | 27 |
| Hydroxypropyl cellulose | 10 |
| Water | 100 |
Take by weighing pregelatinized Starch and mannitol, mixed 80 mesh sieves; Take by weighing active component (being ilaprazole calcium), sodium bicarbonate and sodium hydroxide, mixed 60 mesh sieves; With above-mentioned both mixing.Take by weighing hydroxypropyl cellulose, use the small amount of thermal aqueous dispersion, add the water dissolution of prescription surplus again, slurrying (10% (m/m)).With said mixture material and slurry system soft material, and soft material is extruded round as a ball.Major parameter is controlled to be: the particle diameter mould is 0.5mm, and extruding rotating speed is 30-40rpm, and round as a ball rotating speed is 1500-2000rpm.Make micropellets 498.9g, yield is 100.0%.30 ℃ of following convection dryings or fluid bed drying.
Embodiment 6: extrude the micropellets that the spheronization preparation contains ilaprazole zinc
Table 7 contains the micropellets prescription of ilaprazole zinc
| Material | Amount (g) |
| Pre-paying starch | 150 |
| Mannitol | 150 |
| Ilaprazole zinc | 72 |
| Aluminium hydroxide | 100 |
| Hydroxypropyl cellulose | 5 |
| Water | 100 |
Take by weighing pregelatinized Starch and mannitol, mixed 100 mesh sieves; Take by weighing active component (being ilaprazole zinc) and aluminium hydroxide, mixed 100 mesh sieves; With above-mentioned both mixing.Take by weighing hydroxypropyl cellulose, use the small amount of thermal aqueous dispersion, add the water dissolution of prescription surplus again, slurrying (5% (m/m)).With said mixture material and slurry system soft material, and soft material is extruded round as a ball.Major parameter is controlled to be: the particle diameter mould is 0.2mm, and extruding rotating speed is 10-20rpm, and round as a ball rotating speed is 2500-3000rpm.Make micropellets 472.7g, yield is 99.1%.30 ℃ of following convection dryings or fluid bed drying.
Embodiment 7: fluid bed coats sealing coat
Table 8 sealing coat prescription
| Material | Amount (g) |
| Hydroxypropyl methylcellulose 5cp | 20 |
| Pulvis Talci | 100 |
| 80% (v/v) ethanol water | 600 |
| The micropellets that contains active component | 300 |
Get the micropellets that contains active component of embodiment 1 preparation, cross the screening of 40 eye mesh screens.Sealing coat solution need be regulated and carry out coating more than the pH value to 10.5 again, and the sealing coat solution viscosity is 20.24cp, and operating parameter is as shown in table 9.Make micropill 410.7g, yield is 97.8%.
Table 9 technological parameter
Embodiment 8: fluid bed coats sealing coat
Table 10 sealing coat prescription
| Material | Quality (g) |
| The micropellets that contains active component | 120 |
| Hydroxypropyl methylcellulose E5 | 6.0 |
| Pulvis Talci | 3.0 |
| Triethyl citrate | 0.6 |
| Magnesium hydroxide | 1.2 |
| Water | 150 |
| Total amount | 160.8 |
HPMC is disperseed with a small amount of hot water or ethanol, add the suitable quantity of water dissolving again; Pulvis Talci, magnesium hydroxide are mixed with the water of surplus, add above-mentioned HPMC solution and TEC, mixing again, regulate pH=11.0, cross 100 mesh sieves with 4% (m/v) sodium hydrate aqueous solution.Get the micropellets 120g coating sealing coat that contains active component that embodiment 2 makes.Main operating parameters is: temperature of charge: 25-32 ℃; EAT: 30-35 ℃; Hydrojet speed: 5-30rpm; Blower fan frequency: 30-40.Make micropill 125.7g, yield is 96.1%.
Embodiment 9: fluid bed coats enteric coating
Table 11 enteric coating prescription
Get the micropill 200g of the coating sealing coat that embodiment 3 makes,, coat enteric coating then with the screening of 40 eye mesh screens.Operating parameter is as shown in table 12.Make white enteric coated micropill 421.9g, yield is 97.0%.
Table 12 technological parameter
Embodiment 10: fluid bed coats enteric coating
Table 13 enteric coating prescription
In
L30D-55, add 4% (m/v) sodium hydrate aqueous solution 6.5mL, under agitation add polyethylene glycol 6000; After GMS, an amount of hot water of Tween 80 usefulness (more than 80 ℃) dissolving, homogenizing under the 3400rpm is supplied remaining water.Treat that solution temperature reduces to room temperature; This solution under agitation is added in
the L30D-55 solution for preparing, crosses 100 mesh sieves.Get the micropill that embodiment 8 makes and coat the enteric coating operation, main operating parameters is: temperature of charge: 27-29 ℃; EAT: 31-32 ℃; Hydrojet speed: 14-31rpm; Blower fan frequency: 30-40.Make light yellow piller 204.6g, yield is 99.8%.
Embodiment 11: tabletting
Adjuvant except that micropill in the table 14 is processed granule, and binding agent is 4% (m/v) starch slurry, the enteric coated micropill and the granules of accessories mix homogeneously that then embodiment 10 are made, tabletting.
Table 14 tablet formulation
| Composition | Amount (g) |
| The micropill that embodiment 5 makes | 200 |
| Pregelatinized Starch | 75 |
| Starch | 100 |
| Mannitol | 60 |
| Microcrystalline Cellulose pH101 | 240 |
| 4% starch slurry | In right amount |
Embodiment 12: drug release determination
Get the tablet that embodiment 11 makes, according to drug release determination method (two appendix XD second methods of Chinese Pharmacopoeia version in 2005), adopt dissolution method second subtraction unit, rotating speed is that per minute 50 changes.Burst size detects in the acid: 900mL is a release medium with sodium chloride salt acid solution (get sodium chloride 2.0g, add hydrochloric acid 7.0mL, add water to 1000mL, adjust pH is 1.2).Operation in accordance with the law in the time of 120 minutes, is got solution 10mL, filters; Get subsequent filtrate as need testing solution, measure, calculate burst size, must not be higher than 10% of labelled amount; Observe whether variable color of micropill, after washing with following isopropyl alcohol-phosphate-buffered liquid medium, (get 0.2mol/L potassium dihydrogen phosphate 250mL, 0.2mol/L sodium hydroxide 118mL with isopropyl alcohol-phosphate buffer; Mix, add water to 1000mL, transferring pH is 6.8.) (volume ratio=30: 70) 900mL is release medium, solution 10mL was got in operation in accordance with the law in the time of 45 minutes, filter, and got subsequent filtrate as need testing solution, measured.Calculate burst size, must not be lower than 75% of labelled amount.
Did two batches of detections, the result is following:
Table 15 ilaprazole sodium enteric-coated pellet tablet release degree result
Claims (10)
1. enteric coated tablet, this enteric coated tablet comprise enteric coated micropill and with pharmaceutically acceptable additive of tablet, said enteric coated micropill comprises micropellets, sealing coat and enteric coat layer, said micropellets comprises ilaprazole or its pharmaceutically acceptable salt and stabilizing agent.
2. enteric coated tablet according to claim 1 is characterized in that, the pharmaceutically acceptable salt of said ilaprazole is ilaprazole sodium, ilaprazole magnesium, ilaprazole lithium, ilaprazole potassium, ilaprazole zinc and/or ilaprazole calcium.
3. enteric coated tablet according to claim 1 and 2; It is characterized in that said stabilizing agent is selected from one or more in magnesium oxide, magnesium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate and the aluminium hydroxide; Preferably, the ratio 0.5～5: 1 of said stabilizing agent and the weight of ilaprazole or its pharmaceutically acceptable salt.
4. according to each described enteric coated tablet in the claim 1 to 3; It is characterized in that; Said micropellets comprises one or more substrate that is selected from oxide, cellulose, organic polymer, inorganic salt and sugar, and optional one or more are selected from the binding agent of hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, syrup, starch, polyvinylpyrrolidone and sodium alginate; Preferably, the weight ratio of said binding agent and substrate is 2～10: 98～90.
5. according to each described enteric coated tablet in the claim 1 to 4, it is characterized in that the particle diameter of said micropellets is the 0.1-2 millimeter, be preferably the 0.2-1.3 millimeter.
6. according to each described enteric coated tablet in the claim 1 to 5; It is characterized in that said sealing coat comprises one or more binding agents that is selected from syrup, Polyethylene Glycol, polyvinyl alcohol, polyvinyl acetate, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, methylcellulose, ethyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone and sodium alginate; One or more are selected from the stabilizing agent of magnesium oxide, magnesium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate and aluminium hydroxide; And optional plasticizer, for example one or more in triethyl citrate, Polyethylene Glycol, dimethyl phthalate, triacetyl glycerine and the dibutyl sebacate; Optional opacifier, for example titanium dioxide; Optional antiplastering aid, for example Pulvis Talci; Preferably, said stabilizing agent is 5～50: 100 with the ratio of the weight of binding agent; The weight of said binding agent can be 3～15% of micropellets weight.
7. according to each described enteric coated micropill in the claim 1 to 6; It is characterized in that; Said enteric coating layer comprises one or more and is selected from cellulose families such as crylic acid resins such as polyethylene kind, EUDRAGIT S100 such as Lac, polyvinyl alcohol acetic acid phthalic acid ester, carboxylic first and second celluloses, the enteric-coating material of cellulose esters, Opadries etc. such as cellulose acetate phthalate ester, hypromellose phthalandione vinegar, hypromellose acetic acid succinate; And optional one or more are selected from the additive of plasticizer, antiplastering aid, lubricant and opacifier; The contained enteric coating material solid content of enteric coating increases weight to the 20-300% of micropellets, is preferably 50-150%.
8. according to each described enteric coated tablet in the claim 1 to 7; It is characterized in that; Said pharmaceutically acceptable additive of tablet is selected from one or more in filler, binding agent, disintegrating agent and the lubricant, for example one or more in starch, sucrose, dextrin, lactose, pregelatinized Starch, microcrystalline Cellulose, inorganic salt, mannitol, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hydroxypropyl emthylcellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, magnesium stearate, micropowder silica gel and the Pulvis Talci.
9. according to the method for preparing of each described enteric coated tablet in the claim 1 to 8, this method for preparing may further comprise the steps:
(1) with enteric coated micropill and pharmaceutically acceptable additive of tablet directly mix, tabletting; Or pharmaceutically acceptable additive of tablet granulated, mix with enteric coated micropill again, tabletting;
(2) randomly, the coated film-coat of tablet or the sugar-coat that step (1) are made.
10. the method for preparing of enteric coated tablet according to claim 9 is characterized in that, the method for preparing of said enteric coated micropill may further comprise the steps:
(1) to extrude the micropellets that the spheronization preparation comprises ilaprazole or its pharmaceutically acceptable salt and stabilizing agent;
(2) on micropellets, coat sealing coat;
(3) on the micropellets that coats sealing coat, coat enteric coat layer.
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| CN108469398A (en) * | 2018-04-27 | 2018-08-31 | 丽珠医药集团股份有限公司 | A kind of dissolution determination method of Iprazole pharmaceutical composition |
| CN111481525A (en) * | 2020-04-21 | 2020-08-04 | 广东一力罗定制药有限公司 | Omeprazole enteric-coated pellet and production process thereof |
| CN114569579A (en) * | 2020-12-02 | 2022-06-03 | 丽珠医药集团股份有限公司 | Enteric-coated pellet, preparation method thereof and preparation containing same |
| CN114569575A (en) * | 2020-12-02 | 2022-06-03 | 丽珠医药集团股份有限公司 | Enteric-coated pellet, preparation method thereof and preparation containing same |
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| CN101836983A (en) * | 2009-03-17 | 2010-09-22 | 北京利乐生制药科技有限公司 | Lansoprazole-containing pharmaceutical preparation and preparation method thereof |
| CN101836985A (en) * | 2009-03-17 | 2010-09-22 | 北京利乐生制药科技有限公司 | L-pantoprazole magnesium-containing pharmaceutical preparation and preparation method |
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