CN114983964B - Cefdinir granule and preparation method thereof - Google Patents

Cefdinir granule and preparation method thereof Download PDF

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Publication number
CN114983964B
CN114983964B CN202210726279.6A CN202210726279A CN114983964B CN 114983964 B CN114983964 B CN 114983964B CN 202210726279 A CN202210726279 A CN 202210726279A CN 114983964 B CN114983964 B CN 114983964B
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cefdinir
sucrose
granules
fatty acid
acid ester
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CN114983964A (en
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陈少波
吴焕玲
马均乐
陈彩焕
赵艳春
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GUANGDONG HENGJIAN PHARMACEUTICAL CO Ltd
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GUANGDONG HENGJIAN PHARMACEUTICAL CO Ltd
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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
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses cefdinir granules and a preparation method thereof, wherein the cefdinir granules comprise the following components in parts by weight: 40-100 parts of cefdinir; 20-50 parts of sucrose fatty acid ester; 350-400 parts of filler; 16-40 parts of disintegrating agent; 1-5 parts of lubricant; 0.5 to 2.5 portions of flavoring agent. The sucrose fatty acid ester and the cefdinir are subjected to powder coating, so that the raw materials can be better included, the stability and the dissolution rate of the cefdinir are improved, meanwhile, the sucrose fatty acid ester can promote the dissolution of the raw materials, the absorption of the cefdinir is accelerated, and the drug effect is more remarkable. Cefdinir is matched with disintegrating agent, filler and lubricant, so that the medicine release is rapid. The cefdinir granules prepared by the invention are subjected to an influence factor test, an acceleration test and a long-term test, and the results show that various product indexes of the sample are stable in the acceleration test and the long-term test, and the cefdinir granules have higher stability and dissolution and are quick in drug release.

Description

Cefdinir granule and preparation method thereof
Technical Field
The invention relates to the technical field of medicinal preparations, in particular to cefdinir granules and a preparation method thereof.
Background
Cefdinir, chemical name (6 r,7 r) -7- [ [ (2-amino-4-thiazolyl) - (oximino) acetyl ] amino ] -3-vinyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid.
Cefdinir belongs to a broad spectrum of oral third generation cephalosporins that produce antibacterial action by inhibiting synthesis of bacterial cell walls. The product has antibacterial activity against both gram-positive and gram-negative bacteria, and is stable against most beta-lactamase enzymes. The cefdinir has strong antibacterial activity on staphylococcus and strong antibacterial effect on enterobacteriaceae bacteria, influenza bacillus, klebsiella pneumoniae, moraxella catarrhalis and the like; has antibacterial activity against anaerobic bacteria; has poor antibacterial effect on enterococcus, pseudomonas aeruginosa, other Pseudomonas, acinetobacter, etc. Can be used for treating mild and moderate infections caused by sensitive bacteria, such as social acquired pneumonia, acute episode of chronic bronchitis, acute maxillary sinusitis, pharyngitis, tonsillitis, otitis media, and uncomplicated skin and soft tissue infections.
Cefdinir bulk drug is yellowish powder, has poor water solubility, is easy to generate static electricity and has poor fluidity, and is unstable under high-temperature and high-humidity conditions, and related substances are rapidly increased to influence the safety and effectiveness of the cefdinir bulk drug. Thus, proper pharmaceutical ingredients become a critical factor affecting the quality of cefdinir formulations. The development of the cefdinir granules consisting of proper raw materials and auxiliary materials can certainly bring positive effects to the safe and effective application of the cefdinir.
According to the cefdinir granule and the preparation method thereof disclosed by the related technology, although citric acid and sodium citrate are selected to adjust the pH value, the absorption of main drugs is promoted, and the antibacterial performance is enhanced, the selected wet granulation process introduces more raw materials to be in contact with a high-temperature high-humidity environment, so that the risk of stability of the cefdinir granule is high. In the cefdinir granules disclosed in the related art, the introduced auxiliary materials are less to a certain extent to increase the stability of the medicine, but the taste of the product is to be improved.
Therefore, it is necessary to provide cefdinir granules with better stability.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems existing in the prior art. Therefore, the cefdinir granule provided by the invention can effectively improve the stability of the cefdinir granule.
The invention also provides a preparation method of the cefdinir granule.
An embodiment of the first aspect of the present invention provides a cefdinir granule, comprising the following components in parts by weight:
the cefdinir granule provided by the embodiment of the invention has at least the following beneficial effects:
The sucrose fatty acid ester and the cefdinir are subjected to powder coating, so that the raw materials can be better included, the stability and the dissolution rate of the cefdinir are improved, meanwhile, the cefdinir can promote the dissolution of the raw materials, the absorption of the cefdinir is accelerated, and the drug effect is more remarkable. The cefdinir is matched with the disintegrating agent, the filler and the lubricant to enable the drug release to be rapid, and the cefdinir granules and the products disclosed by the patent (CN 103284958A, CN 103893132A) prepared by the invention are subjected to an influence factor test, an acceleration test and a long-term test, so that the results show that various product indexes of the sample are stable in the acceleration test and the long-term test, and the quality of the sample is superior to that of the products disclosed by the patent.
According to some embodiments of the invention, the sucrose fatty acid ester comprises at least one of sucrose laurate, sucrose myristate, sucrose palmitate, sucrose stearate, sucrose oleate, sucrose behenate, or sucrose erucate.
According to some embodiments of the invention, the sucrose fatty acid ester is at least one of sucrose laurate, sucrose myristate, sucrose palmitate, sucrose stearate, sucrose oleate.
According to some embodiments of the invention, the sucrose fatty acid ester is sucrose laurate, sucrose stearate, sucrose oleate.
According to some embodiments of the invention, the sucrose fatty acid ester is sucrose laurate.
According to some embodiments of the invention, the filler comprises at least one of dextrin, mannitol, sucrose, microcrystalline cellulose, or corn starch. Thus, the filler is used to improve the compression moldability of the drug while improving the uniformity of the drug content.
According to some embodiments of the invention, the disintegrant comprises at least one of sodium carboxymethyl starch, crospovidone, croscarmellose sodium, carboxymethyl cellulose, and calcium carboxymethyl cellulose. Thus, the disintegrant can cause the particles to disintegrate rapidly in the gastrointestinal fluid to release the drug.
According to some embodiments of the invention, the disintegrant comprises at least one or more of crospovidone, croscarmellose sodium, and carboxymethylcellulose.
According to some embodiments of the invention, the disintegrant comprises a mixture of crospovidone and carboxymethylcellulose.
According to some embodiments of the invention, the lubricant comprises at least one of magnesium stearate, talc, silica.
According to some embodiments of the invention, the flavoring agent comprises at least one of stevioside, sodium saccharin, aspartame, acesulfame potassium, thaumatin, orange essence, or apple essence. Therefore, the addition of the flavoring agent ensures that the cefdinir granules have better taste and enhances the medicine taking compliance of patients.
According to some embodiments of the invention, the flavoring agent comprises a mixture of aspartame, acesulfame potassium, thaumatin and apple flavour combinations. Therefore, the mixture of the combination of the aspartame, the acesulfame potassium, the thaumatin and the apple essence is selected as the flavoring agent, so that the cefdinir granule has cool and sweet taste and better compliance.
According to a second aspect of the present invention, there is provided a method for preparing cefdinir granules, comprising the steps of:
s1: sieving cefdinir, filler and disintegrating agent respectively for use; adding sucrose fatty acid ester into ethanol for dissolving for standby;
S2: fluidizing and mixing the sieved cefdinir, filler and disintegrating agent uniformly, and then coating the powder by using sucrose fatty acid ester ethanol solution; the coating temperature is 45-55 ℃, and after coating, the granules are dried, and the moisture content of the granules is controlled to be less than 0.2%;
S3: and (3) finishing the dried granules with 16-28 meshes, adding a lubricant and a flavoring agent, mixing, detecting the content of an intermediate, and subpackaging.
The preparation method of the cefdinir granules has at least the following beneficial effects:
The cefdinir granule prepared by the invention has better taste masking effect by adopting a powder coating process, the sucrose fatty acid ester dissolved by ethanol is selected to be free from introducing moisture, the contact between a main medicine and moisture can be better reduced by the sucrose fatty acid ester inclusion raw material, the temperature required by drying can be reduced by volatilizing the ethanol, and the stability of the cefdinir granule is improved.
According to some embodiments of the invention, in step S1, the mesh number of the sieving is: cefdinir passes through 80-150 meshes, the filler is crushed and passes through 80-200 meshes, and the disintegrating agent passes through 60-150 meshes. Therefore, the cefdinir, the filler and the disintegrating agent after being respectively sieved are mixed, so that the uniformity is better and the stability is enhanced.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Detailed Description
The following are specific embodiments of the present invention, and the technical solutions of the present invention will be further described with reference to the embodiments, but the present invention is not limited to these embodiments.
The reagents, methods and apparatus employed in the present invention, unless otherwise specified, are all conventional in the art.
Example 1
Example 1 provides cefdinir granules, the component contents of which are shown in table 1, and the preparation method is as follows:
S1: sieving cefdinir with 100 mesh sieve, pulverizing sucrose, sieving with 120 mesh sieve, sieving crospovidone and carboxymethyl cellulose with 80 mesh sieve, adding sucrose laurate into 60 deg.C ethanol, dissolving and dispersing to obtain 25% concentration solution;
S2: and adding cefdinir, sucrose, crospovidone and carboxymethyl cellulose into a powder coating machine, fluidizing and uniformly mixing, and then carrying out powder coating by using 25% of sucrose laurate solution with the concentration of 60 ℃ and heat preservation. The coating temperature is 45-55 ℃, and after coating, the heating and drying are closed for 30min, and the moisture of the particles is controlled to be less than 0.2%;
S3: and (3) drying the granules to obtain 20-mesh granules, adding silicon dioxide, aspartame, acesulfame potassium, thaumatin and apple essence, fully mixing, detecting the content of an intermediate, and sub-packaging.
Examples 2 to 4
Examples 2-4 provide a series of cefdinir granules, the preparation method is the same as example 1, and the component content is shown in Table 1.
TABLE 1 component content of examples 1-4
Example 5
The invention provides cefdinir granules, the preparation method and the component content of which are the same as those of example 4, wherein the difference is that the sucrose fatty acid ester is sucrose stearate.
Example 6
The invention provides cefdinir granules, the preparation method and the component content of which are the same as those of example 4, wherein the difference is that sucrose fatty acid ester is sucrose behenate.
Comparative example 1
Comparative example 1 provides a cefdinir granule prepared as per example 4 of CN103284958 a as a sample:
sieving cefdinir with 120 mesh sieve, pulverizing sucrose, and sieving with 80 mesh sieve: weighing cefdinir, pregelatinized starch, hydroxypropyl cellulose sodium and sucrose, mixing, making soft material with 50% ethanol, granulating with 20 mesh wet method, air drying at 65deg.C, sieving with 80 mesh sieve, detecting intermediate product, and packaging.
Comparative example 2
Comparative example 2A cefdinir granule was provided and a sample was prepared according to example 1 of CN 103893132A
Sieving cefdinir with 200 mesh sieve for use, sieving sucrose, sodium cyclamate, citric acid and sodium citrate with 80 mesh sieve for use, and dissolving carmine in 20% ethanol solution for use. Uniformly mixing cefdinir, sucrose, sodium cyclamate, citric acid and sodium citrate, preparing a soft material by using a 20% ethanol solution in which carmine is dissolved, granulating by a 24-mesh wet method, drying the granules by blowing at 60 ℃ for 2-3 hours, finishing the dried granules by 20 meshes, controlling the moisture of the granules to be less than 0.5%, adding double concentrated apple essence, fully mixing, detecting the content of an intermediate, and subpackaging to obtain the finished product.
Comparative example 3
Comparative example 3 provides a cefdinir granule, the preparation method and component content of which are the same as those of example 4, except that hydroxypropyl cellulose is used instead of sucrose laurate.
Performance testing
Stability test
1. Influence factor test
And (5) examining the properties of different samples, dissolution, moisture, main medicine content and related substances. Placing conditions: the medicine is tested according to the guidelines of the stability test of four 9001 raw medicines and preparations in the 2020 edition of Chinese pharmacopoeia. The cefdinir granules of preparation example 4 of the present invention were tested under high temperature, high humidity and intense light irradiation environments, respectively, and samples were examined according to the above items.
1.1 Light test
Taking cefdinir granules of preparation example 4 of the invention, placing the cefdinir granules under the condition of illumination intensity of 4500+/-500 lx, irradiating the cefdinir granules for 10 days with near ultraviolet lamp energy of 90 mu w/cm 2, sampling and measuring each index on the 5 th day and comparing the measuring results of each index on the 10 th day with the measuring results of 0 day.
1.2 High temperature test
Taking cefdinir granules of the preparation example 4 of the invention, placing the cefdinir granules at a constant temperature of 50 ℃ for 10 days, sampling and measuring each index on the 5 th day and 10 th day respectively, and comparing the measuring results with the results on the 0 th day.
1.3 High humidity test
Taking cefdinir granules of the preparation example 4 of the invention, placing the cefdinir granules at 25 ℃,75% RH and 92.5% RH for 10 days under constant humidity, sampling and measuring each index on the 5 th day and 10 th day respectively, and comparing the measurement results with the measurement results on the 0 th day. The results of the influence factor tests are shown in Table 2.
TABLE 2 results of sample influence factor tests prepared in example 4
Note that: '/' indicates undetected.
Conclusion: the test results of the cefdinir granule influencing factors show that: the product is placed under the condition of strong light, the appearance color of the product is slightly deepened, related substances are slightly increased, and other indexes are unchanged; the product is placed under the high temperature condition of 60 ℃, the appearance color of the product is hardly changed, related substances are slightly increased, and other indexes are not changed, so that the product is indicated to be preserved in a dark environment at normal temperature. The indexes are not changed after detection under the conditions of 40 ℃ and high humidity, and the sample is stable.
2. Acceleration test
Samples of the invention of example 4, comparative example 1, comparative example 2 and comparative example 3 were packaged on the market, and placed under the conditions of 40 ℃ + -2 ℃ and 75% + -5% RH relative humidity for 6 months, and sampled sequentially at 1,2,3 and 6 months, respectively, and were measured according to stability key inspection items. The results of the acceleration test are shown in Table 3.
TABLE 3 accelerated test results
Conclusion: as can be seen from the data in Table 3, the product of example 4 of the present invention has stable indexes at 40+ -2deg.C and 75% + -5% RH, and has better impurity control, faster release and better stability than other control samples. In addition, the product of example 4 of the present invention was more compliant than the control samples (comparative example 1, comparative example 2) in terms of mouthfeel using the same method of oral administration.
Compared with sucrose behenate used in example 6, the product in example 5 has better coating effect on raw materials due to sucrose stearate powder, less impurity change and better stability.
3. Long-term test
Samples of the invention of example 4, comparative example 1, comparative example 2 and comparative example 3 were packaged on the market, and placed under the conditions of a temperature of 25 ℃ + -2 ℃ and a relative humidity of 60% + -10% RH for 12 months, and sampled in the order of 3 rd, 6 th, 9 th and 12 th months, respectively, and were measured according to stability key investigation items. The long-term test results are shown in Table 4.
TABLE 4 long-term test results
Conclusion: as can be seen from the data in Table 4, the product of example 4 of the present invention has stable indexes at the temperature of 25+ -2deg.C and relative humidity of 60% + -10% RH, and has more excellent impurity control, faster release and better stability than other control samples. Compared with comparative example 3, in example 4 of the present invention, the sucrose fatty acid ester powder has better coating effect on the raw materials after being added, the impurity change is small, the stability is better, and the change trend of the long-term stability is the same as that of the acceleration test.
In addition, the same infusion method was used, and samples at different time points compared the mouthfeel of the product of example 4 of the present invention with the comparative sample, and the product of example 4 of the present invention had better compliance.
The present invention has been described in detail with reference to the above embodiments, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of those skilled in the art without departing from the spirit of the present invention.

Claims (2)

1. The cefdinir granule is characterized by comprising the following components in parts by weight:
the sucrose fatty acid ester is one of sucrose laurate, sucrose stearate or sucrose behenate;
The filler is sucrose; the disintegrating agent consists of 15 parts of carboxymethyl cellulose and 20 parts of crospovidone; the lubricant is silicon dioxide; the flavoring agent consists of 0.4 part of aspartame, 0.3 part of acesulfame potassium, 0.3 part of thaumatin and 0.77 part of apple essence;
the cefdinir granule is prepared by the following method:
S1: sieving cefdinir with 100 mesh sieve, pulverizing sucrose, sieving with 120 mesh sieve, sieving crospovidone and carboxymethyl cellulose with 80 mesh sieve, adding sucrose fatty acid ester into 60 deg.C ethanol, dissolving and dispersing to obtain 25% concentration solution;
S2: adding cefdinir, sucrose, crospovidone and carboxymethyl cellulose into a powder coating machine, fluidizing and uniformly mixing, and then carrying out powder coating by using 25% sucrose fatty acid ester solution with the concentration of 60 ℃ and the temperature being kept; the coating temperature is 45-55 ℃, and after coating, the heating and drying are closed for 30min, and the moisture of the particles is controlled to be less than 0.2%;
S3: and (3) drying the granules to obtain 20-mesh granules, adding silicon dioxide, aspartame, acesulfame potassium, thaumatin and apple essence, fully mixing, detecting the content of an intermediate, and sub-packaging.
2. The preparation method of cefdinir granules according to claim 1, comprising the steps of:
S1: sieving cefdinir with 100 mesh sieve, pulverizing sucrose, sieving with 120 mesh sieve, sieving crospovidone and carboxymethyl cellulose with 80 mesh sieve, adding sucrose fatty acid ester into 60 deg.C ethanol, dissolving and dispersing to obtain 25% concentration solution;
S2: adding cefdinir, sucrose, crospovidone and carboxymethyl cellulose into a powder coating machine, fluidizing and uniformly mixing, and then carrying out powder coating by using 25% sucrose fatty acid ester solution with the concentration of 60 ℃ and the temperature being kept; the coating temperature is 45-55 ℃, and after coating, the heating and drying are closed for 30min, and the moisture of the particles is controlled to be less than 0.2%;
S3: and (3) drying the granules to obtain 20-mesh granules, adding silicon dioxide, aspartame, acesulfame potassium, thaumatin and apple essence, fully mixing, detecting the content of an intermediate, and sub-packaging.
CN202210726279.6A 2022-06-24 2022-06-24 Cefdinir granule and preparation method thereof Active CN114983964B (en)

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Citations (6)

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Publication number Priority date Publication date Assignee Title
CN1418091A (en) * 2000-03-08 2003-05-14 Awd.药品股份有限两合公司 Pharmaceutical preparations
CN101816635A (en) * 2010-05-17 2010-09-01 广东恒健制药有限公司 Cephalosporin suspension granule and preparation method thereof
CN103284958A (en) * 2013-06-21 2013-09-11 山东罗欣药业股份有限公司 Cefdinir composition granule and preparation method thereof
CN103893132A (en) * 2014-04-25 2014-07-02 优胜美特制药有限公司 Cefdinir granule and preparation technology thereof
CN104586854A (en) * 2014-12-24 2015-05-06 石家庄四药有限公司 Cefuroxime axetil pharmaceutical composition and preparation method thereof
WO2015152190A1 (en) * 2014-03-31 2015-10-08 富山化学工業株式会社 Granular solid formulation containing cephalosporin ester, and method for producing same

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090197855A1 (en) * 2006-05-01 2009-08-06 Makarand Krishnakumar Avachat Pharmaceutical compositions of cefdinir

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1418091A (en) * 2000-03-08 2003-05-14 Awd.药品股份有限两合公司 Pharmaceutical preparations
CN101816635A (en) * 2010-05-17 2010-09-01 广东恒健制药有限公司 Cephalosporin suspension granule and preparation method thereof
CN103284958A (en) * 2013-06-21 2013-09-11 山东罗欣药业股份有限公司 Cefdinir composition granule and preparation method thereof
WO2015152190A1 (en) * 2014-03-31 2015-10-08 富山化学工業株式会社 Granular solid formulation containing cephalosporin ester, and method for producing same
CN103893132A (en) * 2014-04-25 2014-07-02 优胜美特制药有限公司 Cefdinir granule and preparation technology thereof
CN104586854A (en) * 2014-12-24 2015-05-06 石家庄四药有限公司 Cefuroxime axetil pharmaceutical composition and preparation method thereof

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