CN103565765B - The ibuprofen mouth of compound essence powder coating release by different level collapses the preparation of piller - Google Patents
The ibuprofen mouth of compound essence powder coating release by different level collapses the preparation of piller Download PDFInfo
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Abstract
The present invention relates to the ibuprofen oral disintegrate piller of compound essence powder coating, by different level release, cover ibuprofen acid in the oral cavity, and present release by different level.First ibuprofen is micronized to particle diameter and is less than 200 μm, carry out three kinds of powder coatings respectively, (1) oral cavity release, carries out compound essence powder coating to part ibuprofen, obtains Orally disintegrating piller (I); (2) release in stomach, carries out gastric solubility powder coating to part ibuprofen, obtains Orally disintegrating piller (II); (3) release in intestinal, carries out enteric powder coating to part ibuprofen, obtains Orally disintegrating piller (III); Tabletting after Orally disintegrating piller (I), (II), (III) are mixed with vertical compression filler, compound disintegrating agent, fluidizer, lubricant and correctives.Prepare three kinds of Orally disintegrating pillers, cover ibuprofen acid in the oral cavity, and present the release by different level of oral cavity, harmonization of the stomach intestinal, without obvious grittiness.
Description
One, technical field:
The invention belongs to technical field of medicine.Be specifically related to one release by different level, compound essence powder coating prepares ibuprofen oral disintegrate piller, then direct compression.
Two, background technology:
Ibuprofen is phenylpropionic acid NSAID (non-steroidal anti-inflammatory drug), has stronger antiinflammatory, analgesia and refrigeration function, and it becomes four large pillar products on China's antipyretic analgesic market together with acetaminophen, aspirin, diclofenac.But ibuprofen has himself advantage in clinical practice.Be all febrifuge safely and effectively, when body temperature is higher than 39.2 DEG C, ibuprofen is more effective than the acetaminophen with dosage, and the time of bringing down a fever is long.Pharmacodynamic study proves, the analgesia of ibuprofen, refrigeration function are aspirin and 28 times and 20 times respectively, its untoward reaction is fewer and light than aspirin, through the clinical practice of more than 30 years, ibuprofen has withstood the test of time and the masses, is used as the drug of first choice of current critical anti-inflammatory joint disease.
The research of current domestic ibuprofen dosage form mainly contains tablet, granule, oral solution, oral slow-releasing preparation, injection, preparation capable of permeating skin, rectal suppository, solid dispersion etc., conventional dosage forms is large to GI irritation, bioavailability is low, and the side effect such as Nausea and vomiting, erythra is larger.And the feature of novel ibuprofen oral disintegrating tablets is:
1 absorbs soon, and bioavailability is high.Oral cavity disintegration tablet can affect the rate of dissolution of medicine, particularly on the impact of insoluble medicine rate of dissolution, therefore makes the bioavailability that oral cavity disintegration tablet can improve medicine.Oral cavity disintegration tablet is applicable to need onset rapidly, and valid density differs larger medicine with poisoning concentration, and some war wound emergency treatment medicines, NSAID (non-steroidal anti-inflammatory drug), spasmolytic Bendectin and analgesic etc. are all relatively applicable to making oral cavity disintegration tablet; Other medicine is in comparatively plateau for a long time as blood drug level, then easily produce drug resistance, after making oral cavity disintegration tablet, then can overcome this problem, produce good therapeutic effect.
2 taking conveniences.Oral cavity disintegration tablet need not use water delivery service, saliva can make its disintegrate or dissolving, both can swallow by conventional tablet, can be placed in water again and take after disintegrate, also can not need to take medicine with water swallow, be particularly useful for old man, children's, the patient of dysphagia and the inconvenient person that fetches water and take medicine and provide conveniently, if adopt certain method to improve the mouthfeel of preparation in the preparation, then greatly can improve the drug compliance of child patient, solve the problem of taking baby ' difficulty.
3 intestinals are residual few, and side effect is low.As lower than the gastrointestinal reaction rate of diclofenac and naproxen ordinary tablet in piroxicam rapidly dissolving tablet.The rapid disintegrate of antipyretic analgesic aspirin, ibuprofen speed disintegrating tablet energy before medicine arrives gastrointestinal tract is also dispersed into trickle granule, and cause medicine in the distribution of gastrointestinal tract large area, absorption point increases, thus reduces medicine to gastrointestinal local excitation.
4 first pass effects avoiding liver.Due to oral cavity disintegration tablet rapid disintegrate in mouth, except major part enters except gastrointestinal tract with swallowing act, also have considerable part direct oral cavity to absorb, thus rapid-action, first pass effect is little.
5 local therapeutic effects.Normal oral solid preparation (tablet, capsule) arrives stomach bottom rapid deflation, is difficult to the Targeting Effect reaching stomach.The oral cavity disintegration tablet of anion exchange resin-containing, because it is at dissolved in oral cavity, resin is even at gastrin IR cells, and the medicine of 10%, Entogastric lingering 5.5 hours, can carry out topical therapeutic to helicobacter pylori.
Along with the development of spray drying technology, solid solution technology and direct compression of full-powder technology, and the exploitation of excellent adjuvant, oral cavity disintegration tablet by its uniqueness feature and develop rapidly, there is good market prospect.
Ibuprofen crude drug itself has particularity, and its acid can produce strong impulse to throat, and therefore the mouthfeel of ibuprofen oral disintegrating tablets is the difficult point of formulation and technology.In order to cover the acid of crude drug, the method usually adopted has and adds correctives.Correctives generally comprises sweeting agent, aromatic, mucilage and effervescent four class.Sweeting agent can cover the salty, puckery of medicine and bitterness; Aromatic is in a medicament in order to improve spice and the essence of the abnormal smells from the patient of medicament; Mucilage has the character that thickness relaxes, and can disturb the sense of taste of taste bud and have the effect of taste masking; Effervescent system utilizes organic acid (as citric acid, tartaric acid) to mix with sodium bicarbonate, meets after water and produces great amount of carbon dioxide, because carbon dioxide is water-soluble in acid, can benumb taste bud and taste masking.By add correctives promote taste bud to sweet, sour, cool, hot, cunning impression and nervi olfactory to the impression of fragrance, obscure the brain sense of taste, cover the taste of medicine itself, therefore add the method that correctives taste masking is the consideration of preparation override, effective to the medicine of the micro-hardship of low dose of mouthfeel, but to heavy dose of and that bitterness is strong medicine, taste masking technology targetedly must be adopted on the basis adding correctives.Conventional taste masking technology has the technology such as granulation, lipid microsphere, regulation and control pH, resin complexes, coating, reduces medicine and dissolves in saliva and discharge, reduce the combination of drug molecule and taste bud, reach the object of taste masking.
CN101978955A discloses a kind of Dextral ibuprofen amino acid salt tablets and preparation method thereof, adopt wet method, dry granulation tabletting, direct powder compression, also coating can be carried out to tablet, ordinary tablet, chewable tablet, effervescent tablet, oral instant-dissolving tablet, coated tablet and Film coated tablets can be prepared into, main component is Dexibuprofen amino acid salt, and onset is rapid, few side effects.
CN102488681A discloses a kind of ibuprofen diphenhydramine oral cavity disintegration tablet and preparation method thereof, and prescription composition is ibuprofen 40%, diphhydramine hydrochloride 5% or diphenhydramine citrate 7.6%, filler 35%-40%, disintegrating agent 6%-12%, gas-producing disintegrant 0-5%, binding agent 1%-2%, surfactant 1%-2.5%, lubricant 1%-1.5%, sweeting agent 0.7%-2,5% and aromatic 0-0.5%; Prepared oral cavity disintegration tablet meets the prescription of oral cavity disintegration tablet, and appearance looks elegant, mouthfeel is good, steady quality.
CN101455653A discloses a kind of arginine ibuprofen oral disintegrating tablets, is made up of active component arginine Ibuprofen and suitable pharmaceutic adjuvant.Its percentage by weight is arginine Ibuprofen 20%-60%, adjuvant 40%-80%.Adjuvant comprises: the mixture of one or more in diluent (filler), disintegrating agent, binding agent, wetting agent, lubricant, correctives, coloring agent, gas-producing disintegrant.Correctives, mucilage, packaging technique or the above-mentioned multiple method of integrated use is adopted to cover the acid of principal agent.
Powder coating technology is a kind of novel packaging technique, cover the bad of medicine and smell taste, improve the stability of preparation and improve the compatibility stability of medicine, the object that compound essence can reach dual taste masking is added in coating material, the use of compound essence simultaneously brings unique armaticity to oral cavity disintegration tablet, add the compliance of patient medication, be more applicable to old man and child's medication.The present invention wishes to prepare a kind of ibuprofen oral disintegrating tablets, does not need to carry out precursor modification to ibuprofen, but adopts technique simple compound essence powder coating technology to prepare Orally disintegrating piller, reaches the object covering ibuprofen acid.Wherein adopt different coating materials to carry out powder coating, the Orally-disintegrating tablet piller of different release approach can be obtained, make ibuprofen present with different levels drug release behavior.
Three, summary of the invention:
The object of the invention is: provide a kind of taking convenience, mouthfeel is excellent, has unique fragrance, and Orally disintegrating piller of release by different level and preparation method thereof.
Object of the present invention can be achieved through the following technical solutions.
The preparation method that the ibuprofen mouth of compound essence powder coating of the present invention release by different level collapses piller is: first carry out micronization to ibuprofen, then three kinds of multi-form powder coatings are carried out to recipe quantity ibuprofen, obtain three kinds of Orally disintegrating pillers, tabletting after being mixed homogeneously with vertical compression filler, compound disintegrating agent, fluidizer, lubricant and correctives by three kinds of Orally disintegrating pillers.
Carry out micronization to ibuprofen, object promotes that it dissolves and stripping, controls its particle diameter and be less than 200 μm.Take recipe quantity micronization principal agent, adopt following steps to carry out the powder coating of principal agent:
(1) compound essence powder coating, obtains Orally disintegrating piller (I), mainly release in the oral cavity;
(2) gastric solubility coating material powder coating, obtains Orally disintegrating piller (II), mainly release under one's belt;
(3) enteric-coating material powder coating, obtains Orally disintegrating piller (III), mainly release in intestinal.
Compound essence powder coating technology compound essence is scattered in absorption, dissolves or be melted in coating material, adopts fluid bed or fusion method to carry out powder coating.Powder coating is carried out to the micronized ibuprofen of Part I.Compound essence is selected from orange flavor, Fructus Citri Limoniae essence, Fructus Citri tangerinae essence, Mint Essence, kiwi fruit essence, spice, Herba Menthae Rotundifoliae two kinds or more; Coating material is selected from one or more in acrylic resin, ethylene copolymer, cyclodextrin and derivant thereof, Rikemal B 200, ethylene copolymer, gelatin; The ratio of compound essence rain coating material is 1: 10 ~ 3: 7, preferably 1: 7 ~ 1: 3; Compound essence powder coating makes principal agent increase weight as 2-20%, and preferred principal agent weightening finish is 5-15%, more preferably 6%-12%; The order number of the Orally disintegrating piller (I) that compound essence powder coating is prepared is 20 ~ 60 orders, preferably 35 ~ 50 orders.
In gastric solubility coating material powder coating, coating material is selected from one or more in cellulose derivative, polyvidone, crylic acid resin, AEA; Gastric solubility coating material powder coating makes principal agent increase weight as 40-150%, and preferred principal agent weightening finish is 60-130%, more preferably 80%-110%; The order number of the Orally disintegrating piller (II) that gastric solubility coating material powder coating is prepared is 20 ~ 50 orders, preferably 30 ~ 45 orders.。
Enteric-soluble coating material is selected from one or more in Lac, CAP, acrylic resin, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methylcellulose acetate succinate; Powder coating makes principal agent increase weight as 30-150%, and preferred principal agent weightening finish is 65-135%, more preferably 85%-120%; The order number of the Orally disintegrating piller (III) that enteric-soluble coating material powder coating is prepared is 20 ~ 50 orders, preferably 30 ~ 45 orders.。
Compound disintegrating agent described in the present invention is selected from one or more of the hypromellose of low replacement, cross-linking sodium carboxymethyl cellulose, crospovidone and carboxymethyl starch sodium, conbined usage gas-producing disintegrant simultaneously; Gas-producing disintegrant be selected from sodium bicarbonate and citric acid, sodium bicarbonate and tartaric acid, sodium bicarbonate and citric acid and sodium bicarbonate and fumaric acid one or more.Wherein gas-producing disintegrant not only has and promotes the effect of disintegrate, and gas-producing disintegrant is also a kind of correctives simultaneously, adds gas-producing disintegrant and also have and cover ibuprofen acid and irritating effect in oral cavity disintegration tablet.
The filler of vertical compression described in the present invention is microcrystalline Cellulose, spray in dry lactose, Lactis Anhydrous, pre-paying starch one or more; Fluidizer and lubricant are one or more in micropowder silica gel, aerosil, magnesium stearate, calcium hydrogen phosphate, Polyethylene Glycol; Correctives is one or more in aspartame, sorbitol, mannitol.
Three kinds of multi-form powder coatings are carried out to ibuprofen, has prepared 3 kinds of Orally disintegrating pillers, respectively release in oral cavity, harmonization of the stomach intestinal.Ibuprofen on the one hand owing to discharging in oral cavity reduces, ibuprofen is reduced the zest of the oral mucosa of throat, simultaneously because the ibuprofen discharged in the oral cavity is through compound essence powder coating, the armaticity of the uniqueness of compound essence and powder coating technology dually can cover the acid of ibuprofen; Orally disintegrating pillers different on the other hand, makes ibuprofen present release by different level, reduces the irritation on mucous membrane of ibuprofen to each position.
Four, detailed description of the invention:
Embodiment 1
Preparation method: carry out comminution by gas stream micronization to ibuprofen, controls its particle diameter and is less than 200 μm.Micronization ibuprofen is divided into three parts, and carry out powder coating respectively, step is as follows:
(1) compound essence powder coating, 20g micronization ibuprofen is placed in fluid bed, orange flavor and Fructus Citri Limoniae essence are dispersed in Eudragit E 100 coating material (ratio of compound essence and coating material is 1: 3), make principal agent increase weight 10%, obtain 35 ~ 50 object Orally disintegrating pillers (I);
(2) gastric solubility coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. IV, acrylic resin for coating material, makes principal agent increase weight 90%, obtains 30 ~ 45 object Orally disintegrating pillers (II);
(3) enteric-coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. II, acrylic resin for coating material, makes principal agent increase weight 100%, obtains 30 ~ 45 object Orally disintegrating pillers (III).
Direct compression after medicine after powder coating is mixed homogeneously with recipe quantity Lactis Anhydrous, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, citric acid, sodium bicarbonate, aspartame, magnesium stearate and micropowder silica gel.
Embodiment 2
Preparation method: carry out ball mill pulverizing micronization to ibuprofen, controls its particle diameter and is less than 200 μm.Micronization ibuprofen is divided into three parts, and carry out powder coating respectively, step is as follows:
(1) compound essence powder coating, 20g micronization ibuprofen is placed in fluid bed, orange flavor and Fructus Citri tangerinae essence are dispersed in Eudragit E 100 and acrylic resin NE30D mixing coating material (ratio of compound essence and coating material is 1: 4), make principal agent increase weight 10%, obtain 35 ~ 50 object Orally disintegrating pillers (I);
(2) gastric solubility coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. IV, acrylic resin for coating material, makes principal agent increase weight 90%, obtains 30 ~ 45 object Orally disintegrating pillers (II);
(3) enteric-coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. II, acrylic resin for coating material, makes principal agent increase weight 100%, obtains 30 ~ 45 object Orally disintegrating pillers (III).
Direct compression after medicine after powder coating is mixed homogeneously with recipe quantity Lactis Anhydrous, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, citric acid, sodium bicarbonate, aspartame, magnesium stearate and micropowder silica gel.
Embodiment 3
Preparation method: carry out ball mill pulverizing micronization to ibuprofen, controls its particle diameter and is less than 200 μm.Micronization ibuprofen is divided into three parts, and carry out powder coating respectively, step is as follows:
(1) compound essence powder coating, 20g micronization ibuprofen is placed in fluid bed, orange flavor and Fructus Citri tangerinae essence are dispersed in Eudragit E 100 coating material (ratio of compound essence and coating material is 1: 7), make principal agent increase weight 8%, obtain 35 ~ 50 object Orally disintegrating pillers (I);
(2) gastric solubility coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. IV, acrylic resin for coating material, makes principal agent increase weight 100%, obtains 30 ~ 45 object Orally disintegrating pillers (II);
(3) enteric-coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. II, acrylic resin for coating material, makes principal agent increase weight 120%, obtains 30 ~ 45 object Orally disintegrating pillers (III).
Direct compression after medicine after powder coating is mixed homogeneously with recipe quantity Lactis Anhydrous, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, citric acid, sodium bicarbonate, aspartame, magnesium stearate and micropowder silica gel.
Embodiment 4
Preparation method: carry out comminution by gas stream micronization to ibuprofen, controls its particle diameter and is less than 200 μm.Micronization ibuprofen is divided into three parts, and carry out powder coating respectively, step is as follows:
(1) compound essence powder coating, 20g micronization ibuprofen is placed in fluid bed, kiwi fruit essence and Fructus Citri tangerinae essence are dispersed in Eudragit E 100 and acrylic resin NE30D mixing coating material (ratio of compound essence and coating material is 1: 4), make principal agent increase weight 10%, obtain 35 ~ 50 object Orally disintegrating pillers (I);
(2) gastric solubility coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. IV, acrylic resin for coating material, makes principal agent increase weight 100%, obtains 30 ~ 45 object Orally disintegrating pillers (II);
(3) enteric-coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. II, acrylic resin for coating material, makes principal agent increase weight 100%, obtains 30 ~ 45 object Orally disintegrating pillers (III).
Direct compression after medicine after powder coating is mixed homogeneously with recipe quantity Lactis Anhydrous, microcrystalline Cellulose, mannitol, cross-linking sodium carboxymethyl cellulose, citric acid, sodium bicarbonate, aspartame, magnesium stearate and micropowder silica gel.
Embodiment 5
Preparation method: carry out comminution by gas stream micronization to ibuprofen, controls its particle diameter and is less than 200 μm.Micronization ibuprofen is divided into three parts, and carry out powder coating respectively, step is as follows:
(1) compound essence powder coating, 20g micronization ibuprofen is placed in fluid bed, kiwi fruit essence and Fructus Citri tangerinae essence are dispersed in Eudragit E 100 coating material (ratio of compound essence and coating material is 1: 3), make principal agent increase weight 10%, obtain 35 ~ 50 object Orally disintegrating pillers (I);
(2) gastric solubility coating material powder coating, is placed in fluid bed by 15g micronization ibuprofen, with No. IV, acrylic resin for coating material, makes principal agent increase weight 100%, obtains 30 ~ 45 object Orally disintegrating pillers (II);
(3) enteric-coating material powder coating, 15g micronization ibuprofen is placed in fluid bed, and hydroxypropyl methyl cellulose phthalate is coating material, makes principal agent increase weight 110%, obtains 30 ~ 45 object Orally disintegrating pillers (III).
Direct compression after medicine after powder coating is mixed homogeneously with recipe quantity Lactis Anhydrous, microcrystalline Cellulose, mannitol, carboxymethyl starch sodium, citric acid, sodium bicarbonate, aspartame, magnesium stearate and micropowder silica gel.
Claims (10)
1. the ibuprofen mouth of compound essence powder coating release by different level collapses the preparation method of little pellet, it is characterized in that ibuprofen micronization, three kinds of multi-form powder coatings are carried out to ibuprofen, obtain three kinds of Orally disintegrating pillers, tabletting after being mixed homogeneously with vertical compression filler, compound disintegrating agent, fluidizer, lubricant and correctives by three kinds of Orally disintegrating pillers; Described three kinds of multi-form powder coating process are, take recipe quantity micronization principal agent, adopt following steps to carry out the powder coating of principal agent: (1) compound essence powder coating, obtain Orally disintegrating piller (I), principal agent is release in the oral cavity; (2) gastric solubility coating material powder coating, obtain Orally disintegrating piller (II), principal agent is release under one's belt; (3) enteric-coating material powder coating, obtain Orally disintegrating piller (III), principal agent is release in intestinal; Described compound essence powder coating, be compound essence is scattered in coating material to carry out powder coating, coating material is acrylic resin, and the ratio of compound essence and coating material is 1:7 ~ 1:3, and it is 6% ~ 12% that compound essence powder coating makes principal agent increase weight; Described gastric solubility coating material is crylic acid resin; Described enteric-soluble coating material is selected from the one in acrylic resin, hydroxypropyl methyl cellulose phthalate; Described compound disintegrating agent is selected from one or more of low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and carboxymethyl starch sodium, simultaneously conbined usage gas-producing disintegrant, gas-producing disintegrant is selected from one or more in sodium bicarbonate and citric acid, sodium bicarbonate and tartaric acid and sodium bicarbonate and fumaric acid; Described vertical compression filler is microcrystalline Cellulose and Lactis Anhydrous.
2. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, it is characterized in that the micronized particle diameter of ibuprofen is less than 200 μm.
3. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, what it is characterized in that powder coating adopts is fluid bed or fusion method powder coating.
4. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, it is characterized in that described compound essence is selected from orange flavor, Fructus Citri Limoniae essence, Fructus Citri tangerinae essence, Mint Essence, kiwi fruit essence, spice, Herba Menthae Rotundifoliae two kinds or more.
5. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, it is characterized in that the order number of the Orally disintegrating piller (I) that compound essence powder coating is prepared is 35 ~ 50 orders.
6. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, it is characterized in that described gastric solubility coating material powder coating makes principal agent increase weight as 60-130%.
7. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, it is characterized in that the order number of the Orally disintegrating piller (II) that gastric solubility coating material powder coating is prepared is 30 ~ 45 orders.
8. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, it is characterized in that described enteric-soluble coating material powder coating makes principal agent increase weight as 65-135%.
9. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, it is characterized in that the order number of the Orally disintegrating piller (III) that enteric-soluble coating material powder coating is prepared is 30 ~ 45 orders.
10. collapse the preparation method of little pellet according to the ibuprofen mouth of the release by different level of the compound essence powder coating described in claim 1, it is characterized in that described fluidizer and lubricant are one or more in micropowder silica gel, aerosil, magnesium stearate, Polyethylene Glycol; Correctives is one or more in aspartame, sorbitol, mannitol.
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| CN103536538B (en) * | 2013-10-23 | 2016-06-29 | 海南康芝药业股份有限公司 | A kind of expansive pellet of effective taste masking and preparation method thereof |
| CN107184565B (en) * | 2017-06-01 | 2018-04-03 | 海南妙音春制药有限公司 | A kind of preparation method of ibuprofen sustained release capsules |
| CN106983734B (en) * | 2017-06-01 | 2018-09-14 | 海南妙音春制药有限公司 | A kind of ibuprofen sustained release capsules and preparation method thereof |
| CN110917165A (en) * | 2019-12-26 | 2020-03-27 | 北京鑫开元医药科技有限公司海南分公司 | Ibuprofen orally disintegrating tablet and preparation method thereof |
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| CN101548953A (en) * | 2008-04-03 | 2009-10-07 | 上海医药工业研究院 | Medicine granule, preparation method thereof, and preparation containing same |
| CN102327244A (en) * | 2011-09-30 | 2012-01-25 | 杭州康恩贝制药有限公司 | Ambroxol hydrochloride orally disintegrating tablet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101548953A (en) * | 2008-04-03 | 2009-10-07 | 上海医药工业研究院 | Medicine granule, preparation method thereof, and preparation containing same |
| CN102327244A (en) * | 2011-09-30 | 2012-01-25 | 杭州康恩贝制药有限公司 | Ambroxol hydrochloride orally disintegrating tablet and preparation method thereof |
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| Title |
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| 对于口服药物掩味方法的研究进展;张玥等;《中国实用医药》;20080531;第3卷(第13期);第195-196页 * |
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