CN105769773B - Loxoprofen sodium sustained-release pellet - Google Patents
Loxoprofen sodium sustained-release pellet Download PDFInfo
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- CN105769773B CN105769773B CN201610201063.2A CN201610201063A CN105769773B CN 105769773 B CN105769773 B CN 105769773B CN 201610201063 A CN201610201063 A CN 201610201063A CN 105769773 B CN105769773 B CN 105769773B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
Abstract
The invention provides a loxoprofen sodium sustained-release pellet which comprises a drug-loaded pellet core, an isolation layer and a sustained-release layer, wherein the isolation layer is wrapped on the drug-loaded pellet core, and the sustained-release layer is wrapped on the isolation layer. The weight ratio of the drug-loaded pill core to the isolation layer to the slow release layer is 80: 1-15: 2-20. The loxoprofen sodium sustained-release pellet preparation disclosed by the invention has good in-vitro release characteristics, can reduce the administration times, improves the administration compliance of patients, and further can stabilize the blood concentration and reduce the gastrointestinal toxic and side effects of the medicament. The invention also discloses a preparation method of the loxoprofen sodium sustained-release pellet, which has simple process and is easy for industrial production.
Description
Technical Field
The invention belongs to the field of pharmacy, and relates to a loxoprofen sodium sustained-release pellet and a preparation method thereof.
Background
Loxoprofen Sodium (Loxoprofen Sodium), the first propionic acid precursor type nonsteroidal anti-inflammatory drugs (NSAIDs), was first developed by japan co. The medicine is metabolized into trans-OH type active medicine in vivo after oral administration, inhibits biosynthesis of prostaglandin, namely covers active center of enzyme by combining with cyclooxygenase, thereby blocking metabolism of arachidonic acid converted into PG by the enzyme, and plays roles of analgesia, antiphlogosis and antipyresis. Loxoprofen sodium as a novel NSAID is a prodrug which is inactive and is active only after rapid conversion by the liver to trans-OH metabolites, unlike other drugs. The analgesic effect is 20 times of that of indometacin, and the mouse paw carrageenin edema experiment shows that the anti-inflammatory effect is twice of that of the indometacin. The medicine has rapid action, and has strong and lasting effects of relieving pain, diminishing inflammation, and relieving fever. At present, the traditional Chinese medicine composition is mainly used for treating rheumatoid arthritis, osteoarthritis, lumbago, scapulohumeral periarthritis, neck, shoulder and wrist syndrome, pains after operation and tooth extraction, acute upper respiratory inflammation and other diseases.
The loxoprofen sodium comprises loxoprofen sodium anhydrous compound, monohydrate or dihydrate, wherein the loxoprofen sodium dihydrate is collected by the Japanese medicine administration and the standards issued by the ministry of China, and is a water-soluble medicine, and the oral preparation of the medicine which is sold on the market at home and abroad at present is mainly loxoprofen sodium tablet, the dosage is 180mg per day, the loxoprofen sodium tablet is taken in three times, and the use convenience is poor. Compared with the common tablets, the loxoprofen sodium sustained-release pellet has the advantages of stabilizing blood concentration, reducing administration times, improving the compliance of patients in taking medicine, reducing gastrointestinal toxic and side effects induced by the over-strong inhibition effect of prostaglandin generated by over-high blood drug peak concentration and the like. In addition, compared with sustained release tablets (unit drug release systems), the loxoprofen sodium sustained release pellets are used as a multi-unit drug delivery system, and 1) after oral administration, the loxoprofen sodium sustained release pellets are rapidly dispersed in the gastrointestinal tract, so that gastric mucosa injury caused by overhigh local concentration is reduced. 2) The micro-pill can easily pass through the gastric pylorus of the human physiological anatomical structure due to the particle size range of less than 1.5mm, thereby avoiding food effect and administration difference among individuals. 3) The multi-unit drug delivery system avoids the occurrence of 'existence' or 'nonexistence' phenomenon existing in the unit drug delivery system, namely the loss of control of individual unit does not influence the drug delivery behavior of the whole system, thereby having higher safety and tolerance.
The polymer aqueous dispersion has been favored in the pharmaceutical industry field for the eighties of the last century because of its environmental protection, low toxicity, low cost, and significant sustained release. The aqueous dispersions currently commercially available for the coating of sustained and controlled release films mainly comprise acrylic resin-based aqueous dispersions (e.g., Eudragit RL30D, Eudragit RS30D, Eudragit NE30) and ethyl cellulose aqueous dispersions (e.g., Surelease and Aquecoat). Wherein the main components of Eudragit RL30D comprise 30% w/w of ethyl acrylate, methyl methacrylate and trimethylammoninylethyl methacrylate in a molar ratio of 1: 2: 0.2, and the main components of Eudragit RS30D comprise 30% w/w of ethyl acrylate, methyl methacrylate and trimethylammoninylethyl methacrylate in a molar ratio of 1: 2: 0.1. Eudragit NE comprises 28.5% w/w of butyl acrylate to methyl methacrylate in a 2: 1 molar ratio and about 1.5% of a stabiliser (nonionic surfactant nonylphenol polyoxyethylene ether 100). The dispersion of the Surilise (Surelease) mainly comprises ethyl cellulose with the solid content of 25%, and also comprises dibutyl sebacate, oleic acid, ammonia water, light silica gel and the like. The aqueous Aqcoat dispersion had a total solids content of 30% and contained 25% w/w ethylcellulose, sodium lauryl sulfate and 5% cetyl alcohol, relative to the weight of the ethylcellulose, 2.7%.
When the water-based dispersion liquid coating is used for preparing the sustained-release pellets, because the surface area of the pellets is larger, a more serious burst release phenomenon often occurs, the invention adopts the process that the isolating layer is firstly coated on the pellet core by the acid isolating liquid, and then the sustained-release layer is coated by the water-based dispersion liquid to prepare the water-based alkaline medicament loxoprofen sodium sustained-release pellets, the burst release phenomenon is reduced, the sustained-release pellets meeting the requirements of the sustained-release preparation are obtained, and the sustained-release pellets are suitable for sustained-release preparations which are administrated 2 times (sustained-release 12h) in 1 day or are administrated once (sustained-release 24.
Disclosure of Invention
The invention provides a loxoprofen sodium-containing sustained-release pellet and a preparation method thereof, the pellet has slow, stable and controllable in-vitro release rate, good reproducibility and simple preparation process, and is easy for industrial production.
The invention aims to provide a loxoprofen sodium sustained-release pellet. The sustained-release pellet comprises a loxoprofen sodium drug-loaded pellet core, an isolation layer coated on the drug-loaded pellet core and a sustained-release layer coated on the isolation layer. Wherein the weight ratio of the drug-loaded pill core to the isolation layer and the slow release layer is 80: 1-15: 2-20.
The loxoprofen sodium sustained-release pellet is characterized in that the particle size of a drug-carrying pellet core is 0.6-1.5 mm. The drug-loaded pill core comprises the following components in percentage by weight:
the drug-loaded pellet core prescription in the loxoprofen sodium sustained-release pellet is characterized in that the adhesive is one or a mixture of two or more of sucrose, dextrin and pregelatinized starch; the wetting agent is selected from one or two mixtures of water and ethanol.
The loxoprofen sodium sustained-release pellet is characterized in that the isolating layer coating solution is an environment-friendly polymer aqueous solution, and the isolating layer coating solution is prepared from the following components in percentage by weight:
the prescription of the isolating layer coating solution in the loxoprofen sodium sustained-release pellet is characterized in that the common film coating material is one or a mixture of two or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol and polyethylene glycol-polyvinyl alcohol block copolymer; the pH regulator is one or a mixture of two or more of citric acid, tartaric acid, succinic acid, fatty acid, malic acid, oxalic acid, glutaric acid, maleic acid, glutamic acid, mandelic acid and fumaric acid; the plasticizer comprises one or two or more of triethyl citrate, glycerol, propylene glycol, polyethylene glycol, phthalate, dibutyl sebacate and diethyl oxalate; the emulsifier is selected from one or two or more of span, tween, lecithin and sodium dodecyl sulfate.
The preparation method of the isolating layer coating solution in the loxoprofen sodium sustained-release pellet is characterized in that the preparation method of the isolating layer coating solution comprises the steps of preparing a solution of a common film coating material by using distilled water, adding a pH regulator, a plasticizer, an emulsifier and talcum powder, fully stirring, uniformly mixing, adding water to a sufficient amount, and preparing the isolating coating solution with the solid content of 5-20%.
The loxoprofen sodium sustained-release pellet is characterized in that the sustained-release coating solution is an environment-friendly polymer aqueous dispersion solution and is selected from one of ethyl cellulose aqueous dispersion solution and acrylic resin aqueous dispersion solution.
The preparation method of the loxoprofen sodium sustained-release pellet is characterized by comprising the following steps of:
(1) preparing loxoprofen sodium pellet cores: weighing loxoprofen sodium, microcrystalline cellulose and an adhesive according to a proportion, uniformly mixing, and preparing a soft material by using a proper amount of wetting agent; extruding the prepared soft material by an extruder to extrude strip-shaped objects; and rolling the obtained strip-shaped object in a rolling machine to obtain a round pill, drying the round pill by using an oven or a fluidized bed, and sieving the round pill by using a sieve with 18-30 meshes to collect the loxoprofen sodium pill core.
(2) Coating an isolation layer: coating the loxoprofen sodium pellet core with an aqueous isolating solution in a fluidized bed or a centrifugal granulator, wherein the product temperature is 30-60 ℃, the liquid inlet speed is 2-40rmp, drying in the fluidized bed or an oven to obtain the pellet coated with the isolating layer,
(3) coating a slow release layer: and (3) coating the pills coated with the isolating layer with a sustained-release aqueous dispersion liquid in a fluidized bed or a centrifugal granulator, wherein the product temperature is 30-80 ℃, the liquid inlet speed is 5-50 rmp, and drying by the fluidized bed or an oven to obtain the loxoprofen sodium sustained-release pellets.
The release rate of the loxoprofen sodium sustained-release pellet mainly depends on the concentration of the pH regulator in the isolation layer, the coating amount of the isolation layer and the coating amount of the sustained-release layer. Experimental research shows that when the amount of the pH regulator accounts for 10-30% of the solid content of the isolation layer, the coating amount of the isolation layer accounts for 5-10% of the weight of the drug-loaded pellet core, and the coating amount of the slow-release layer accounts for 15-20% of the weight of the drug-loaded pellet core, the release degree range of the prepared loxoprofen sodium slow-release pellet with the release medium of water is as follows: 5-30% (2 hours), 40-70% (5 hours) and 70-90% (10 hours).
In conclusion, the loxoprofen sodium sustained-release pellet provided by the invention not only can inhibit the phenomenon of burst release of loxoprofen sodium which is easily dissolved in water, but also can realize good sustained-release drug release characteristics. The preparation process is simple and easy for industrial production.
The research of the loxoprofen sodium sustained-release pellet has great significance, the loxoprofen sodium sustained-release pellet not only reduces the irritation to the gastrointestinal tract, but also reduces the administration times, improves the compliance of patients in taking medicine, and simultaneously slowly releases the medicine at a speed which can not only reach the required blood concentration, but also keep stable, thereby avoiding the side effect of the common tablet caused by the blood peak phenomenon.
Drawings
FIG. 1 shows the release curves of loxoprofen sodium sustained-release pellet capsules provided in examples 1 to 5
Fig. 2 shows the release curve of the loxoprofen sodium sustained-release pellet capsule provided in example 6.
Detailed Description
The invention is further explained or illustrated by the following examples. The examples are only for the purpose of aiding understanding of the present invention, and should not be construed as limiting the spirit and scope of the present invention.
Example 1 loxoprofen sodium sustained release pellet capsule (2000 capsules)
Prescription:
1) medicine-carrying pill core
2) Isolating layer coating liquid
3) Slow-release coating liquid
Stilsilk aqueous dispersion 180g
120g of distilled water
The preparation process comprises the following steps:
1) preparing a drug-loaded pill core: the loxoprofen sodium, the starch and the microcrystalline cellulose are respectively sieved by a sieve of 80 meshes, evenly mixed according to the formula proportion, added with 50 percent ethanol to prepare a soft material, extruded by a sieve plate of an extruder to obtain strips, the strips are put into a spheronizer to be spheronized to obtain round particles, dried for 12 hours at 50 ℃, and sieved by a pellet of 0.6-1.25 mm to obtain the drug-containing pellet core, and the drug-containing pellet core obtained is smooth and clean in appearance, round and high in hardness and is suitable for coating.
2) Preparing an isolating layer coating solution: weighing 130g of HPMC-E5, preparing into solution with distilled water, adding polyethylene glycol 3350, span 80, span 85 and citric acid according to the prescription amount, stirring for dissolving, adding talcum powder according to the prescription amount, stirring uniformly, finally supplementing distilled water to 300g, and stirring uniformly for later use.
3) Preparing a slow-release coating solution: taking the prescribed amount of the Sulisi and the distilled water, and uniformly stirring for later use.
4) Coating the prepared drug-loaded pill core by an isolation layer by adopting a bottom-spraying fluidized bed process, wherein the material temperature is 35-40 ℃, the liquid inlet amount is 15rmp, the liquid spraying pressure is 15-20 bar, and the air blowing amount is 80m3And h, increasing the weight of the isolating layer by 6-9%.
5) Coating the pills with the isolating layer by adopting a bottom-spraying fluidized bed process to form a slow-release layer, wherein the material temperature is 40-45 ℃, the liquid inlet amount is 20rmp, the liquid spraying pressure is 15-20 bar, and the air blowing amount is 80m3And h, increasing the weight of the slow release layer by 16-18%. Drying for 2-12 h at 60 ℃ by a fluidized bed or an oven, taking out and filling into No. 0 capsules.
Example 2 loxoprofen sodium sustained release pellet capsule (2000 capsules)
Prescription:
1) the drug-loaded pellet core is the same as that in example 1
2) Isolating layer coating liquid
3) Slow-release coating liquid
Aqueous dispersion of sulise 240
160g of distilled water
The preparation process comprises the following steps: the same as in example 1.
EXAMPLE 3 loxoprofen sodium sustained-release pellet Capsule (2000 pellets)
Prescription:
1) the drug-loaded pellet core is the same as that in example 1
2) Isolating layer coating liquid
3) Slow-release coating liquid
Stilsilk aqueous dispersion 270g
180g of distilled water
The preparation process comprises the following steps: the same as in example 1.
Example 4 loxoprofen sodium sustained release pellet capsules (2000 capsules)
Prescription:
1) medicine-carrying pill core
2) Isolating layer coating liquid
3) Slow-release coating liquid
Stilsilk aqueous dispersion 270g
180g of distilled water
The preparation process comprises the following steps: the same as in example 1.
Example 5 loxoprofen sodium sustained-release pellet capsules (2000 capsules)
Prescription:
1) medicine carrying pill core: the same as in example 1.
2) Isolating layer coating liquid
3) Slow-release coating liquid
The preparation process comprises the following steps: the process is the same as that of example 1 except that the weight of the coating of the sustained-release layer is increased by 16-19%.
Example 6 loxoprofen sodium sustained release pellet capsules (2000 capsules)
Prescription:
1) medicine-carrying pill core
2) Insulating layer
3) Sustained release layer
Stilsilk aqueous dispersion 270g
Distilled water 180g
The preparation process comprises the following steps: the same as in example 1.
EXAMPLE 7 Release test
The in vitro release rates of the sustained-release pellet capsules prepared in examples 1 to 6 were measured by a dissolution rate measurement method (appendix X C of second part of 2010 edition of chinese pharmacopoeia) paddle method apparatus according to the release rate measurement method (first method XD of appendix of second part of 2010 edition of chinese pharmacopoeia). Taking 900mL of purified water as a medium, rotating at 100 rpm, taking 5mL of solution in 1, 2, 4, 5, 6, 8, 10 and 12h respectively, filtering through a 0.45 μm microporous membrane, and instantly supplementing the medium with the same volume in an operation container. Taking the subsequent filtrate, diluting twice, and respectively measuring absorbance at 223nm wavelength according to spectrophotometry (appendix IV A of second part of the 2010 edition of Chinese pharmacopoeia); taking a proper amount of loxoprofen sodium reference substance, preparing an aqueous solution with the concentration of 30 mu g/mL as a reference substance solution, and measuring the absorbance at the wavelength of 223 nm. The cumulative release was calculated and the results are shown in FIGS. 1 and 2.
From the results of fig. 1 and 2, it can be seen that the drug release of all loxoprofen sodium sustained-release pellet formulations can last for more than 10 hours, and the release rate of the sustained-release pellets in the release medium of water is in the range: 5-30% (2 hours), 40-70% (5 hours) and 70-90% (10 hours), is suitable for 1 day of administration 2 times (sustained release 12 hours) or 1 day of administration once (sustained release 24 hours) sustained release preparation, can avoid the peak valley phenomenon of the drug concentration, reduce the irritation and injury of the drug to the gastrointestinal tract, reduce the administration frequency of the drug, improve the medication compliance of patients, and the preparation method has simple process, good reproducibility, low equipment requirement and easy industrial production.
Claims (6)
1. The loxoprofen sodium sustained-release pellet is characterized by comprising a loxoprofen sodium drug-loaded pellet core, an acidic isolation layer and a sustained-release layer, wherein the acidic isolation layer is wrapped on the drug-loaded pellet core, and the sustained-release layer is wrapped on the acidic isolation layer, and the weight ratio of the drug-loaded pellet core to the acidic isolation layer to the sustained-release layer is 80: 1-15: 2-20; the sustained-release pellet can be directly used as a preparation for oral administration, and can also be filled into an empty capsule for oral administration;
the acidic isolation layer coating solution is an environment-friendly polymer aqueous solution, and the acidic isolation layer coating solution has the following formula in percentage by weight:
the slow release coating liquid is an environment-friendly polymer aqueous dispersion liquid, and is selected from one or a mixture of two of ethyl cellulose aqueous dispersion liquid and acrylic resin aqueous dispersion liquid.
2. The loxoprofen sodium sustained-release pellet as claimed in claim 1, wherein the particle size of the drug-loaded pellet core is 0.6-1.5 mm, and the prescription of the drug-loaded pellet core is as follows by weight percent:
3. the loxoprofen sodium sustained-release pellet core carrying medicine formula in the loxoprofen sodium sustained-release pellet as claimed in claim 2, wherein the adhesive is one or a mixture of two or more of sucrose, dextrin and pregelatinized starch; the wetting agent is selected from one or two mixtures of water and ethanol.
4. The loxoprofen sodium sustained-release pellet as claimed in claim 1, wherein the common film coating material is one or a mixture of two or more of hypromellose, hydroxypropyl cellulose, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol and polyethylene glycol-polyvinyl alcohol block copolymer; the pH regulator is one or a mixture of two or more of citric acid, tartaric acid, succinic acid, fatty acid, malic acid, oxalic acid, glutaric acid, maleic acid, glutamic acid, mandelic acid and fumaric acid; the plasticizer comprises one or two or more of triethyl citrate, glycerol, propylene glycol, polyethylene glycol, phthalate, dibutyl sebacate and diethyl oxalate; the emulsifier is selected from one or two or more of span, tween, lecithin and sodium dodecyl sulfate.
5. The loxoprofen sodium sustained-release pellet as claimed in claim 1, wherein the acidic isolation layer coating solution is prepared by preparing a solution of a common film coating material with distilled water, adding a pH regulator, a plasticizer, an emulsifier and talc powder, stirring thoroughly, mixing well, and adding distilled water to a sufficient amount to prepare an isolation coating solution with a solid content of 5-20%.
6. The loxoprofen sodium sustained-release pellet as claimed in claim 1, wherein the preparation method comprises the following steps:
(1) preparing loxoprofen sodium pellet cores: weighing loxoprofen sodium, microcrystalline cellulose and an adhesive according to a proportion, uniformly mixing, and preparing a soft material by using a proper amount of wetting agent; extruding the prepared soft material by an extruder to extrude strip-shaped objects; rounding the obtained strip-shaped object in a rounding machine to obtain a round pill, drying the round pill by an oven or a fluidized bed, and sieving the round pill by a sieve with 18-30 meshes to collect a loxoprofen sodium pill core;
(2) coating an acid isolation layer: coating the loxoprofen sodium pellet core with an aqueous acidic isolating solution in a fluidized bed or a centrifugal granulator, wherein the product temperature is 30-60 ℃, the liquid inlet speed is 2-40rmp, and drying in the fluidized bed or an oven to obtain pellets coated with the isolating layer;
(3) coating a slow release layer: and (3) coating the pills coated with the isolating layer with a sustained-release aqueous dispersion liquid in a fluidized bed or a centrifugal granulator, wherein the product temperature is 30-80 ℃, the liquid inlet speed is 5-50 rmp, and drying by the fluidized bed or an oven to obtain the loxoprofen sodium sustained-release pellets.
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| CN113750077B (en) * | 2021-10-16 | 2022-12-20 | 河南省人民医院 | Amlodipine besylate sustained-release pellet and preparation method thereof |
| CN114983973B (en) * | 2022-05-31 | 2023-05-05 | 石家庄四药有限公司 | Urapidil sustained-release capsule and preparation method thereof |
| CN116650444B (en) * | 2023-07-31 | 2023-10-31 | 国药集团川抗制药有限公司 | Tacrolimus slow-release drug and preparation method thereof |
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|---|---|---|---|---|
| CN1628648A (en) * | 2004-08-26 | 2005-06-22 | 复旦大学 | Loxoprofen sodium sustained release preparation |
| CN101489536A (en) * | 2006-07-19 | 2009-07-22 | 旭化成化学株式会社 | Process for producing spherical elementary granule containing readily water-soluble drug |
| CN102525989A (en) * | 2011-01-04 | 2012-07-04 | 北京天衡药物研究院 | Loxoprofen sodium matrix sustained-release tablet |
| JP2014111565A (en) * | 2012-11-09 | 2014-06-19 | Taisho Pharmaceutical Co Ltd | Pharmaceutical composition |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1628648A (en) * | 2004-08-26 | 2005-06-22 | 复旦大学 | Loxoprofen sodium sustained release preparation |
| CN101489536A (en) * | 2006-07-19 | 2009-07-22 | 旭化成化学株式会社 | Process for producing spherical elementary granule containing readily water-soluble drug |
| CN102525989A (en) * | 2011-01-04 | 2012-07-04 | 北京天衡药物研究院 | Loxoprofen sodium matrix sustained-release tablet |
| JP2014111565A (en) * | 2012-11-09 | 2014-06-19 | Taisho Pharmaceutical Co Ltd | Pharmaceutical composition |
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| Title |
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| 离心造粒法制备洛索洛芬钠缓释微丸及体外释放度考察;陈云;《中国药师》;20110131;第14卷(第11期);第84页"摘要"和"1 仪器与试药"，第85页"2.3"和"2.4" * |
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