CN102860985B - Tebipenem pivoxil oral preparation and preparation method thereof - Google Patents
Tebipenem pivoxil oral preparation and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a tebipenem pivoxil-containing oral preparation and a preparation method of the tebipenem pivoxil-containing oral preparation. The preparation provided by the invention consists of tebipenem pivoxil and a pharmaceutic adjuvant as the active components. The pharmaceutic adjuvant contains beta-cyclodextrin. The tebipenem pivoxil oral preparation provided by the invention overcomes the defects that the grit feeling is produced when the tebipenem pivoxil oral preparation is taken, the patient compliance is poor and the preparation technology is complicate in the prior art, so that the tebipenem pivoxil oral preparation is an excellent preparation with good taste, high dissolvability, good stability and simple preparation technology.
Description
Technical field
The invention belongs to carbapenem antibiotics field, be specifically related to a kind of Tebipenem pivoxil oral preparation and preparation method thereof.
Background technology
Tebipenem pivoxil (Tebipenem Pivoxil), chemistry (1R by name, 5S, 6S)-1-methyl-6-[(1R)-1-ethoxy]-2-[1-(1,3-thiazoline-2-base) azetidine-3-base] sulfo--1-carbon penicillin-2-alkene-3-carboxylic acid pivalic acid methyl ester, structural formula as shown in Equation 1:
Tebipenem pivoxil, as first oral formulations product of carbapenem antibiotic, first develops listing by Japanese MingZhi fruit Co., Ltd in August, 2009.This medical instrument has lower Mlc, not easily causes the appearance of bacterial drug resistance; Side effect is little, and drug safety is high, can be used for treating childhood infection.
There is amorphous form and crystal habit in tebipenem pivoxil, the good but poor stability of the tebipenem pivoxil dissolubility of amorphous form, is unsuitable for preparing oral drug preparation; The tebipenem pivoxil good stability of crystal habit, but in water, dissolubility is poor.In addition, tebipenem pivoxil mouthfeel is bitter and have abnormal flavour, and conventionally can not add the bad mouthfeel that correctives carrys out masking agents, causes the Compliance of patient poor, is especially unfavorable for child's administration.
The JP200435518 of Wyeth Lederle Co., Ltd. of Japan application, discloses granular preparations for oral administration containing tebipenem pivoxil hiding bitterness and preparation method thereof.Described granular preparations for oral administration is by gastric solubility coating base, and such as, methacrylic acid aminoalkyl ester copolymer or polyvinyl acetal diethylin acetas carry out coatedly hiding bitterness.After a step comminutor pelletize; the phenomenon that partial particulate is kept afloat is had in water; take mouthfeel bad; therefore need to carry out secondary granulation to obtained granule, could improve and take mouthfeel, technique is more loaded down with trivial details; there is the problems such as differences between batches are large, production cost is high; and it is more in suspension state to be distributed to insoluble matter in water, has grittiness, children taking poor compliance when taking.
In prescription disclosed in tebipenem pivoxil granula subtilis Japanese description, adjuvant used is: the copolymer of microcrystalline Cellulose, hydroxypropyl cellulose, methylcellulose, Pulvis Talci, ethyl cellulose, spermol, sodium lauryl sulphate, ethyl acrylate and methyl methacrylate, thermally coupled distillation columns, triethyl citrate, castor sugar, aspartame, pigment, spice.By carrying out dissolution experiment discovery to commercialized product, in its medicinal liquid, insoluble matter is more in suspension state, therefore, still there is the problem taking grittiness, children taking poor compliance.
Summary of the invention
Therefore, for prior art Problems existing, main purpose of the present invention is to provide a kind of poor taste can covering tebipenem pivoxil, can improve again the Tebipenem pivoxil oral preparation of patient consumes's compliance.Another object of the present invention is to provide a kind of formulation and technology simple, be beneficial to the Tebipenem pivoxil oral preparation preparation method of industrial operation.
According to first goal of the invention, the invention provides a kind of oral formulations comprising tebipenem pivoxil, it is characterized in that: described preparation forms by as the tebipenem pivoxil of active component and pharmaceutic adjuvant, and described pharmaceutic adjuvant comprises beta-schardinger dextrin-.
Wherein:
Tebipenem pivoxil (in tebipenem) is 1: 2 ~ 8 with the weight ratio of beta-schardinger dextrin-, is preferably 1: 3 ~ 5.
Oral formulations of the present invention can be granule or dry suspension.Described pharmaceutic adjuvant also comprises filler, disintegrating agent and sweeting agent, correctives, color element, described filler includes but not limited to sucrose, lactose, mannitol, sorbitol, erythritol, xylitol, described disintegrating agent includes but not limited to polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, described sweeting agent includes but not limited to Sucralose, aspartame, saccharin sodium, stevioside, protein sugar, described correctives includes but not limited to orange flavor, flavoring orange essence, strawberry essence, cherry essence, milk chocolate essence, cream flavour, described pigment includes but not limited to amaranth, carmine, lemon yellow, sunset yellow and indigo.
Preferably, in described Tebipenem pivoxil oral preparation, the percentage by weight of each component is: tebipenem pivoxil (in tebipenem) 10%, beta-schardinger dextrin-20 ~ 80%, filler 5 ~ 50%, disintegrating agent 0 ~ 15%, sweeting agent 0 ~ 5%, correctives 0 ~ 5%, pigment is appropriate.
Further, in described Tebipenem pivoxil oral preparation, the percentage by weight of each component is preferably: tebipenem pivoxil (in tebipenem) 10%, beta-schardinger dextrin-30 ~ 50%, filler 20-40%, disintegrating agent 4 ~ 10%, sweeting agent 0.5-2%, correctives 0.5-2%, pigment is appropriate.
Tebipenem pivoxil oral preparation of the present invention, comments trial to test by mouthfeel, and mouthfeel can acceptance be 95%, and takes and there is not grittiness, greatly improves the mouthfeel of Tebipenem pivoxil oral preparation, improves patient consumes's compliance.
According to goal of the invention two, the invention provides and a kind ofly prepare the method comprising Tebipenem pivoxil oral preparation, first by the tebipenem pivoxil of recipe quantity and beta-schardinger dextrin-mixing, fully mix with other pharmaceutic adjuvant again, then, according to different preparation formulation, can granulate, be distributed into bag, be prepared into granule; Or mixed powder direct packaging becomes bag, is prepared into dry suspension.
Preparation method technique of the present invention is simple, does not need special installation, with low cost, with short production cycle, is easy to accomplish scale production.
As is known to those skilled in the art, cyclodextrin has clathration to guest pharmaceutical molecule, thus increase dissolubility and the dissolution of medicine, or cover the bad stink of medicine, but the selection of enclose material and inclusion method is most important, because they can affect enclose efficiency, and the stability of clathrate.
Tebipenem pivoxil molecular weight is 497.63, beyond being suitable for the cyclodextrin inclusion compound molecular weight scope of application 100 ~ 400, alpha-cyclodextrin due to molecule cavity internal diameter less, be not suitable for carrying out enclose to this medicine, and molecule cavity internal diameter and all larger gamma-cyclodextrin of water solublity are not easy to obtain due to price, neither enclose material first-selected.Inventor adopts beta-schardinger dextrin-comparatively cheap and easy to get and derivant thereof to be that the enclose of representative to tebipenem pivoxil is investigated:
1, beta-schardinger dextrin-is adopted to be enclose material
(1) saturated water solution method is adopted to carry out enclose
Experimentation:
Prescription 1 and 2 takes recipe quantity pure water, is heated to 60 DEG C, and the beta-schardinger dextrin-adding recipe quantity dissolves, and obtains beta-schardinger dextrin-saturated solution, saturated solution is cooled to 40 DEG C; Drip tebipenem pivoxil (a small amount of 95% dissolve with ethanol) medicinal liquid, enclose is stirred 2 hours in 38 ~ 40 DEG C of saturated solutions, enclose liquid is light yellow transparent liquid, stops stirring and leaving standstill, and the standing rear enclose solution of observation has no obvious clathrate precipitation and produces.
Prescription 3 reduces amount of solution, carries out enclose experiment to medicine, but does not also produce obvious sediment in enclose solution.
Experiment proves: adopt saturated water solution method to carry out enclose to tebipenem pivoxil, not easily separates out clathrate precipitation, namely can not obtain solid clathrates.But prove by experiment, tebipenem pivoxil, through beta-cyclodextrin inclusion compound, has obvious effect to raising tebipenem pivoxil dissolubility.
(2) polishing is adopted to carry out enclose
Experimentation: take beta-schardinger dextrin-22.8g, tebipenem pivoxil 10g, puts in mortar and grinds, and obtains mixed inclusion thing.
Experimental result: measure (see accompanying drawing 4) through DSC, tebipenem pivoxil characteristic peak is comparatively obvious, illustrates and does not form tebipenem pivoxil Benexate Hydrochloride,
As can be seen from above-mentioned experimental result, adopt the enclose means that two kinds conventional: saturated water solution method and polishing all can not obtain good solid clathrates.
(3) physical mixed method
Accidental, the direct mixture of the present inventor to tebipenem pivoxil and beta-schardinger dextrin-carries out DSC mensuration, and unexpected discovery obtains good solid clathrates (see accompanying drawing 3) unexpectedly.Comment trial to test by mouthfeel, gained clathrate mouthfeel is better, and acceptance is more than 90%.
The rate of charge of the present inventor to tebipenem pivoxil and beta-schardinger dextrin-is investigated, find when tebipenem pivoxil is (in tebipenem, when being greater than 1: 2 with the weight ratio of beta-schardinger dextrin-down together), discovery can not cover bitter taste of drug well, and acceptance is lower than 90%; When the weight ratio of tebipenem pivoxil and beta-schardinger dextrin-is less than 1: 8, well can cover the bad mouthfeel of medicine, but find that in medicinal liquid, insoluble matter is more, taken grittiness, mouthfeel acceptance is also lower than 90%; When the weight ratio of tebipenem pivoxil and beta-schardinger dextrin-is 1: 2 ~ 8, tebipenem pivoxil and beta-schardinger dextrin-can form good clathrate, and drug administration mouthfeel acceptance is greater than 90%, can cover bitterness preferably, without obvious grittiness when taking; When the weight ratio of tebipenem pivoxil and beta-schardinger dextrin-is 1: 3 ~ 5, drug administration mouthfeel acceptance is greater than 95%, well can cover bitterness, without grittiness when taking.Therefore, in the present invention, the weight ratio of tebipenem pivoxil and beta-schardinger dextrin-is 1: 2 ~ 8, is preferably 1: 3 ~ 5.
2, cyclodextrin derivative is adopted to be enclose material
Inventor take HP-β-CD as representative, investigates the enclose of cyclodextrin derivative to tebipenem pivoxil, experimentation and experimental result as follows:
Experimentation: take HP-β-CD 56g and be dissolved in 200ml 40 DEG C of water, add tebipenem pivoxil 20g to stir, constant temperature stirs enclose 2 hours, enclose liquid carries out spraying dry in spray dryer, inlet temperature controls at 70-80 DEG C, outlet temperature controls at 40-45 DEG C, obtains the pulverous clathrate of tebipenem pivoxil.
Experimental result: comment trial to test by mouthfeel, gained clathrate mouthfeel is better, and acceptance is more than 90%.
Above-mentioned enclose liquid also obtains the pulverous clathrate of tebipenem pivoxil by freeze-drying, and by sensory test, mouthfeel is better, and acceptance is more than 90%.
Although HP-β-CD can form clathrate with tebipenem pivoxil, covering its poor taste, there is following shortcoming in it: need increase spraying dry or freeze-drier, just solid clathrates can be obtained, operating time is longer, complicated process of preparation, and production cost is high.
Also there is same problem in the cyclodextrin derivative of other highly-water-soluble.Therefore, the present invention selects beta-schardinger dextrin-as enclose material.
In order to obtain, mouthfeel is better, dissolution is high, the Tebipenem pivoxil oral preparation of good stability, and the present inventor screens the kind of other pharmaceutic adjuvant and consumption again.
Generally, the adjuvant use amount that disintegrating agent, filler etc. are conducive to stripping is larger, more easily reaches the effect of rapid disintegrate, but the larger then production cost of adjuvant use amount is higher, and all wishes to reduce production cost in production.
Adding of sweeting agent, correctives, pigment is to cover bitterness more efficiently, and makes medicine have good taste and outward appearance, improves the Compliance of child patient.
Filler of the present invention can be selected from sucrose, lactose, mannitol, sorbitol, erythritol, xylitol, and filler can account for 5 ~ 50% of per unit dosage gross weight, is preferably 20-40%.
Disintegrating agent can be selected from polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, and disintegrating agent accounts for 0 ~ 15% of per unit dosage gross weight, is preferably 4 ~ 10%.
Sweeting agent of the present invention can be selected from Sucralose, aspartame, saccharin sodium, stevioside, protein sugar, and sweeting agent accounts for 0 ~ 5% of per unit dosage gross weight, is preferably 0.5-2%.
Correctives can be selected from orange flavor, flavoring orange essence, strawberry essence, cherry essence, milk chocolate essence, cream flavour, and correctives accounts for 0 ~ 5% of per unit dosage gross weight, is preferably 0.5 ~ 2%.
Pigment can from amaranth, carmine, lemon yellow, sunset yellow and indigo middle selection, and addition in right amount.
Optimizing prescriptions of the present invention, detect through indices, investigate, good mouthfeel, dissolution is high, good stability.
Tebipenem pivoxil oral preparation of the present invention can be granule or dry suspension, is preferably granule.
Accompanying drawing explanation
Fig. 1 is tebipenem pivoxil raw material DSC curve.
Fig. 2 is beta-schardinger dextrin-DSC curve.
Fig. 3 is the embodiment of the present invention 1 gained tebipenem pivoxil-Benexate Hydrochloride DSC curve.
Fig. 4 is polishing gained tebipenem pivoxil-Benexate Hydrochloride DSC curve.
Fig. 5 is tebipenem pivoxil granule of the present invention and commercialized product stripping curve comparison diagram.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further elaborated, but these embodiments do not form any restriction to the present invention.
The preparation of embodiment 1 tebipenem pivoxil-Benexate Hydrochloride
Take tebipenem pivoxil 10g and beta-schardinger dextrin-30g, fully mix, then carry out DSC mensuration, the results are shown in Figure 3.
Test result shows, can obtain good tebipenem pivoxil-Benexate Hydrochloride by physical mixed method.
Embodiment 2 tebipenem pivoxil granule 50mg/0.5g
Prescription (1000 bags):
Remarks: in tebipenem pivoxil in preparation total amount, 1g tebipenem is equivalent to 1.3g tebipenem pivoxil.(lower same) operation:
1. take raw material and the beta-schardinger dextrin-mixing of recipe quantity, more fully mix with other adjuvants;
2. after the abundant mix homogeneously of supplementary material, add the appropriate water soft material containing pigment, 16 mesh sieves granulations at boiling drier inner drying, inlet temperature controls at≤60 DEG C, temperature of charge controls at≤40 DEG C, and dry granule, through 14 order granulate, adds essence and is mixed to get tebipenem pivoxil granule.
Embodiment 3: tebipenem pivoxil granule 50mg/0.5g
Prescription (1000 bags):
Operation is with embodiment 2.
Embodiment 4: tebipenem pivoxil granule 50mg/0.5g
Prescription (1000 bags):
Operation is with embodiment 2.
Embodiment 5: tebipenem pivoxil granule 50mg/0.5g
Prescription (1000 bags):
Operation is with embodiment 2.
Embodiment 6: tebipenem pivoxil dry suspension 50mg/0.5g
Prescription (1000 bags):
Operation:
Take the raw material of recipe quantity and beta-schardinger dextrin-mixing, then add essence after fully mixing with other adjuvants and be mixed to get tebipenem pivoxil dry suspension.
The JP200435518 embodiment that inventor applies for reference to Japanese Wyeth Lederle Co., Ltd., Japanese commercialized product "
operation instructions and just do not add beta-schardinger dextrin-or addition outside scope with reference to the embodiment of the present invention, carried out comparative example design, concrete formulation and technology is shown in embodiment 7 ~ 11:
Embodiment 7 tebipenem pivoxil granule 50mg/0.5g
Tebipenem pivoxil granule prescription is drafted with reference to the prescription in JP200435518 embodiment.
Prescription (1000 bags):
Operation:
1, the raw material and the 120g lactose that take recipe quantity mix, then spray into Eudragit E 100 alcoholic solution in fluid bed in carry out pelletize, inlet temperature controls at≤60 DEG C, and temperature of charge controls at≤40 DEG C, and the gain in weight of obtained coating powder is pelletize product of 30%.
2, the mannitol of the lactose of pelletize product and residue recipe quantity and recipe quantity, aspartame and crospolyvinylpyrrolidone are mixed, then the mixed liquor of hydroxypropyl cellulose alcoholic solution and pigment aqueous solution is sprayed into, pelletize is carried out in fluid bed, inlet temperature controls at≤60 DEG C, temperature of charge controls at≤40 DEG C, adds essence and be mixed to get tebipenem pivoxil granule after drying.
Embodiment 8 tebipenem pivoxil granule: 50mg/0.5g
With reference to Japanese commercialized product "
operation instructions, draft formulation and technology.
Prescription (1000 bags):
Operation:
1. the preparation of binding agent: take the Eudragit E 100 of recipe quantity, hexadecanol, hypromellose be dissolved in appropriate ethanol after stirring and dissolving, then add triethyl citrate, Pulvis Talci, pigment stir, for subsequent use.
2. by raw material, sodium lauryl sulphate, aspartame, sucrose, microcrystalline Cellulose, the auxiliary mix homogeneously of ethyl cellulose, spray into the binding agent prepared and carry out pelletize in fluidized bed prilling seed-coating machine, inlet temperature controls at 60 DEG C, temperature of charge controls at 40 DEG C, and gained granule adds essence and is mixed to get tebipenem pivoxil granule.
Embodiment 9 tebipenem pivoxil granule: 50mg/0.5g (not adding beta-schardinger dextrin-)
Prescription (1000 bags):
Operation:
1. take raw material and other adjuvants of recipe quantity, fully mix;
2. after the abundant mix homogeneously of supplementary material, add the appropriate water soft material containing pigment, 16 mesh sieves granulations at boiling drier inner drying, inlet temperature controls at≤60 DEG C, temperature of charge controls at≤40 DEG C, and dry granule, through 14 order granulate, adds essence and is mixed to get tebipenem pivoxil granule.
Embodiment 10 tebipenem pivoxil granule: 50mg/0.5g (tebipenem pivoxil and beta-schardinger dextrin-weight ratio are 1: 1)
Prescription (1000 bags):
Operation:
With embodiment 2.
Embodiment 11 tebipenem pivoxil granule: 50mg/0.5g (tebipenem pivoxil and beta-schardinger dextrin-weight ratio are 1: 8.5)
Prescription (1000 bags):
Operation: with embodiment 2.
Following examples comment trial to test and dissolution determination by mouthfeel, have absolutely proved that Tebipenem pivoxil oral preparation of the present invention is obtained for very big improvement in mouthfeel and stripping, have improve patient and take compliance.
Embodiment 12 mouthfeel comments trial to test
Take sample in embodiment 2 ~ 11 respectively, each 0.5g, add appropriate warm water respectively and make sample be suspendible or basic supernatant liquid state.Carry out commenting trial to test in some health adults, the result shown in following table gives patient the percentage ratio to its mouthfeel.
Compare by testing above, tebipenem pivoxil granule of the present invention, dry suspension and commercialized product, and the mouthfeel of the tebipenem pivoxil granule to obtain with reference to JP200435518 patented method can acceptance all more than 95%, but tebipenem pivoxil granule of the present invention and dry suspension are taken and are not had or substantially do not have grittiness.The tebipenem pivoxil granule mouthfeel obtained outside scope is poor, has taken grittiness.
Embodiment 13 dissolution determination
(1) granule
Embodiment 2 ~ 5,7 ~ 11 gained tebipenem pivoxil granule samples, with reference to dissolution method (Chinese Pharmacopoeia version in 2010 two annex X C second methods), with the citrate-phosphate disodium hydrogen buffer of pH4.0 for dissolution medium, rotating speed is 75 turns per minute, through 15 minutes time, gets solution appropriate, add stripping medium to scale, shake up.According to ultraviolet visible spectrophotometry (Chinese Pharmacopoeia version in 2010 two annex IV A), measure absorbance at the wavelength place of 322nm; Test data sees the following form:
Result clearly illustrates that tebipenem pivoxil granule dissolution of the present invention is good.
(2) dry suspension
Embodiment 6 gained tebipenem pivoxil dry suspension sample, with reference to dissolution method (Chinese Pharmacopoeia version in 2010 two annex X C second methods), with the citrate-phosphate disodium hydrogen buffer of pH4.0 for dissolution medium, rotating speed is 75 turns per minute, appropriate respectively at getting solution time 5,10,15,20,30,45 (min), add stripping medium to scale, shake up.According to ultraviolet visible spectrophotometry (Chinese Pharmacopoeia version in 2010 two annex IV A), measure absorbance at the wavelength place of 322nm; Test data sees the following form
Illustrate that gained tebipenem pivoxil dry suspension dissolution of the present invention is good.
Embodiment 14 dissolution contrast test
Respectively commercialized product and product of the present invention (the embodiment 2 product) dissolution in 4 kinds of dissolution mediums are contrasted, the results are shown in following table:
Medium: the hydrochloric acid (pH1.2) of water, 0.1mol/L, the citrate buffer of pH4.0 and the phosphate buffer of pH6.8
Accompanying drawing 5 is shown in stripping curve contrast.
Above-mentioned experimental result shows, in the citrate medium of pH4.0 and the hydrochloric acid medium of 0.1mol/L (pH1.2), product of the present invention is similar to the stripping curve of commercialized product, and in the phosphate medium of water and pH6.8, product dissolution rate of the present invention is higher than commercialized product.
Embodiment 15 stability test
With the embodiment of the present invention 2 product for representative, carry out accelerated stability and investigated and long-time stability investigation.
(1) accelerated stability
Experiment condition: adopt simulation listing packaging, at 40 DEG C ± 2 DEG C, investigate 6 months under 75%RH ± 5%RH condition.
Experimental result:
Experimental result shows, product stability of the present invention is good.
(2) long-time stability
Experiment condition: adopt simulation listing packaging, at 25 DEG C ± 2 DEG C, investigate 12 months under 60%RH ± 10%RH condition.
Experimental result:
Result of the test shows, product stability of the present invention is good.
To sum up, gained Tebipenem pivoxil oral preparation of the present invention overcomes when taking in prior art grittiness, patient's poor compliance, and the defect of complicated process of preparation, be that a kind of good mouthfeel, dissolution are high, good stability, preparation technology are simple and be applicable to the elegant formulations of suitability for industrialized production.
Claims (1)
1. comprise an oral formulations for tebipenem pivoxil, it is characterized in that: described preparation is granule or dry suspension; Described preparation forms by as the tebipenem pivoxil of active component and pharmaceutic adjuvant, and described pharmaceutic adjuvant is made up of beta-schardinger dextrin-and other pharmaceutic adjuvant,
Wherein:
Tebipenem pivoxil and beta-schardinger dextrin-weight ratio are 1:2 ~ 8;
Other pharmaceutic adjuvant described is selected from filler, disintegrating agent, sweeting agent, correctives and color element;
The percentage by weight of each component of described preparation is: tebipenem pivoxil 10%, beta-schardinger dextrin-20 ~ 80%, filler 5 ~ 50%, disintegrating agent 0 ~ 15%, sweeting agent 0 ~ 5%, correctives 0 ~ 5%, and pigment is appropriate;
Described filler is selected from sucrose, lactose, mannitol, sorbitol, erythritol, xylitol, described disintegrating agent is selected from polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, described sweeting agent is selected from Sucralose, aspartame, saccharin sodium, stevioside, protein sugar, described correctives is selected from orange flavor, flavoring orange essence, strawberry essence, cherry essence, milk chocolate essence, cream flavour, and described pigment is selected from amaranth, carmine, lemon yellow, sunset yellow and indigo;
The preparation method of described preparation is: first by the tebipenem pivoxil of recipe quantity and beta-schardinger dextrin-mixing, more fully mix with other pharmaceutic adjuvant, then, according to different preparation formulation, can granulate, be distributed into bag, be prepared into granule; Or mixed powder direct packaging becomes bag, is prepared into dry suspension.
2. preparation as claimed in claim 1, is characterized in that: tebipenem pivoxil and beta-schardinger dextrin-weight ratio are 1:3 ~ 5.
3. preparation as claimed in claim 1, is characterized in that: the percentage by weight of each component is: tebipenem pivoxil 10%, beta-schardinger dextrin-30 ~ 50%, filler 20-40%, disintegrating agent 4 ~ 10%, sweeting agent 0.5-2%, and correctives 0.5-2%, pigment is appropriate.
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| CN103520120B (en) * | 2013-10-17 | 2015-07-29 | 山东罗欣药业集团股份有限公司 | A kind of L-084 composition granule |
| CN104027310B (en) * | 2013-12-26 | 2016-02-03 | 青岛大学 | A kind of faropenem sodium granules and preparation method thereof |
| CN104069072B (en) * | 2014-07-07 | 2016-09-07 | 山东罗欣药业集团股份有限公司 | A kind of L-084 composition granule |
| BR112019012171B1 (en) * | 2016-12-15 | 2021-02-09 | Spero Therapeutics, Inc | new oral dosage forms of modified and immediate release of tebipenem pivoxil |
| CN109432044B (en) * | 2018-11-27 | 2021-05-11 | 山东省药学科学院 | Tebipenem pivoxil fine granule and preparation method thereof |
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