CN102258495B - Cefprozil tablet and preparation method thereof - Google Patents
Cefprozil tablet and preparation method thereof Download PDFInfo
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- CN102258495B CN102258495B CN2011101954884A CN201110195488A CN102258495B CN 102258495 B CN102258495 B CN 102258495B CN 2011101954884 A CN2011101954884 A CN 2011101954884A CN 201110195488 A CN201110195488 A CN 201110195488A CN 102258495 B CN102258495 B CN 102258495B
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- cefprozil
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- magnesium stearate
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- WDLWHQDACQUCJR-ZAMMOSSLSA-N (6r,7r)-7-[[(2r)-2-azaniumyl-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(e)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)/C=C/C)C(O)=O)=CC=C(O)C=C1 WDLWHQDACQUCJR-ZAMMOSSLSA-N 0.000 title claims abstract description 75
- 229960002580 cefprozil Drugs 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 56
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000011248 coating agent Substances 0.000 claims abstract description 28
- 238000000576 coating method Methods 0.000 claims abstract description 28
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 28
- 239000008101 lactose Substances 0.000 claims abstract description 26
- 239000000843 powder Substances 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 17
- 229940079593 drug Drugs 0.000 claims abstract description 10
- 238000004132 cross linking Methods 0.000 claims description 26
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 26
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 26
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 25
- 239000000047 product Substances 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 19
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 17
- 239000000463 material Substances 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 229920002678 cellulose Polymers 0.000 claims description 9
- 239000001913 cellulose Substances 0.000 claims description 9
- 235000010980 cellulose Nutrition 0.000 claims description 9
- 239000002131 composite material Substances 0.000 claims description 9
- 239000005030 aluminium foil Substances 0.000 claims description 8
- 239000012467 final product Substances 0.000 claims description 8
- 229920003023 plastic Polymers 0.000 claims description 8
- 239000004033 plastic Substances 0.000 claims description 8
- 238000010348 incorporation Methods 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 abstract description 7
- 238000002156 mixing Methods 0.000 abstract description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 abstract description 3
- 229960001681 croscarmellose sodium Drugs 0.000 abstract 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 abstract 2
- 239000011247 coating layer Substances 0.000 abstract 1
- 238000009501 film coating Methods 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 239000010409 thin film Substances 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 55
- 238000012360 testing method Methods 0.000 description 21
- 239000000523 sample Substances 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 238000004090 dissolution Methods 0.000 description 11
- 239000000126 substance Substances 0.000 description 8
- 150000003952 β-lactams Chemical class 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- 230000008859 change Effects 0.000 description 6
- 108090000204 Dipeptidase 1 Proteins 0.000 description 5
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 5
- 229920003081 Povidone K 30 Polymers 0.000 description 5
- 102000006635 beta-lactamase Human genes 0.000 description 5
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- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 238000009702 powder compression Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 2
- 206010001076 Acute sinusitis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
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- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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- 230000001133 acceleration Effects 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
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- 238000004873 anchoring Methods 0.000 description 1
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- 229950009506 penicillinase Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- -1 pressure too hour Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention relates to a cefprozil tablet and a preparation method thereof. The cefprozil tablet comprises a tablet core and a thin-film coating layer. The invention is characterized in that the tablet core consists of cefprozil as an active drug ingredient and used-medicinally adjuvant, wherein the adjuvant comprises cellulose-lactose complex, croscarmellose sodium and magnesium stearate. The preparation method comprises the following steps of: mixing the cefprozil, the cellulose-lactose complex and the croscarmellose sodium, then adding the magnesium stearate, mixing uniformly, tabletting powder by proper pressure and coating.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of cefprozil tablet that is prepared from by medicinal chemicals cefprozil and pharmaceutically acceptable adjuvant and preparation method thereof.
Background technology
Cefprozil is the oral semisynthetic broad-spectrum cephalosporin that contains beta-lactam nucleus of the second filial generation of Shi Guibao company exploitation during by the U.S. hundred, and mechanism of action is the synthetic of anti-bacteria cell wall, makes the antibacterial dissolving of breaking rapidly.This product is all very strong to the antibacterial activity of Gram-positive, negative bacterium and anaerobe, particularly outstanding to gram-positive bacteria activity, be the broad ectrum antibiotic of efficient, low toxicity, anti-enzyme, be used for clinically following light, the grade and moderate infection due to the sensitive organism: 1 upper respiratory tract infection (1) micrococcus scarlatinae pharyngitis/tonsillitis.(2) streptococcus pneumoniae, bloodthirsty hemophilus influenza (comprising the beta-lactamase-producing strain) and moraxelle catarrhalis (comprising the beta-lactamase-producing strain) property otitis media and acute sinusitis.2 lower respiratory infections: the acute bronchitis secondary antibacterial that is caused by streptococcus pneumoniae, bloodthirsty hemophilus influenza (comprising the beta-lactamase-producing strain) and moraxelle catarrhalis (comprising the beta-lactamase-producing strain) infects and acute episode of chronic bronchitis.3 skins and skin soft-tissue infection: non-complex skin and skin soft-tissue infection that staphylococcus aureus (comprise and produce the penicillinase bacterial strain) and micrococcus scarlatinae cause.The oral rear blood drug level of this product is high, and the half-life is about 1.3 hours, and Binding rate of serum protein is about 45%, 24 hours prototype response rate about 70～80% in the urine.Toleration was still good when cefprozil dosage reached 1000mg, was mainly removed by kidney, and oral absorption is good, was linear pharmacokinetics relation.
The beta-lactam nucleus that contains in the cephalosporins structure is the necessary part of antibacterial activity, if the beta-lactam nucleus fracture, then its antibacterial action disappears.But beta-lactam nucleus is the most unsettled part in such compound structure, meet acid, alkali or beta-lactamase and easily hydrolysis occurs and lose antibacterial activity, but and metal ion, temperature and the above-mentioned degradation reaction of oxidant catalysis.The height of the curative effect of medicine is relevant with catabolite with safety clinically.The active medicine that stability is high, purity is high can improve the clinical efficacy of medicine, improves drug safety, reduces the generation of untoward reaction.
Cefprozil, its chemical name is: (6R, 7R)-7-[(R)-2-amino-2-(p-hydroxybenzene) acetylamino]-8-oxo-3-propylene-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid monohydrate, molecular formula: C
18H
19N
3O
5SH
2O, molecular weight: 407.45, structural formula is:
The document of preparation method that relates at present synthetic, the cefprozil intermediate of cefprozil, cefprozil in the patent documentation comprises: EP1638520, US2009048460, US2006149096, CN101225088, CN101024649, CN101058584, EP1638520, WO2004039812, CN101032489, CN101700232, CN101780085.
Chinese patent CN101032489 discloses a kind of Cefprozil dispersible table dosage form and preparation method, and this dispersible tablet is that tabletting makes after evenly being mixed by cefprozil, microcrystalline Cellulose, disintegrating agent, binding agent, micropowder silica gel, magnesium stearate and correctives etc.The shortcoming of this patent is: the long-term shelf-stability of cefprozil is poor, the problem that dissolution is low, the prescription that can not satisfy the prescriptive period.
Chinese patent CN101780085 discloses a kind of Cefprozil medicinal composition, its method by the dry type pelletize makes, after cefprozil and cellulose derivative evenly mix, under the pressure of 0.1～0.25MPa, be pressed into tablet, formation is combined closely, then as required, make tablet, powder, granule and capsule.This pharmaceutical composition can further comprise other conventional adjuvants and mix, and then as required, makes tablet, powder, granule, dry suspension or capsule.This patent system Preparation Method is the dry type prilling, when the preparation tablet, processes again after the pelletize, and with respect to direct compression, this complex process, wayward.
In the preparation and storage process of cefprozil tablet, all to prevent the beta-lactam nucleus open loop degraded of raw material, guarantee the stability of tablet.
The present invention is unexpected to be found, technique of direct powder compression is namely when the cephalo propylene and after can supplying the auxiliary materials and mixing of direct compression, by suitable pressure tabletting, can effectively stop the beta-lactam nucleus open loop degraded of cefprozil, guaranteed stability and the safety of tablet in cefprozil tablet preparation and storage process, and technique of direct powder compression technique is simple, has saved a large amount of human and material resources, meet current energy-saving and emission-reduction, the requirement of low-carbon (LC).
Summary of the invention
The object of the present invention is to provide a kind of cefprozil tablet and preparation method thereof.
The present invention needs emphasis to solve the formation of each component in the medicine and the control parameter in ratio and the preparation process, reduces the beta-lactam nucleus open loop degraded of cefprozil.
For solving the problems of the technologies described above, the present invention is achieved by the following technical solutions:
A kind of cefprozil tablet, comprise label and film-coat layer, it is characterized in that, described label take cefprozil as medicament active composition and pharmaceutically acceptable auxiliaries form, described pharmaceutically acceptable auxiliaries is selected from cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose, magnesium stearate.
In the label prescription of the present invention, cefprozil is principal agent, and cellulose-lactose complex is diluent, and cross-linking sodium carboxymethyl cellulose is disintegrating agent, and magnesium stearate is lubricant.
Among the present invention, the prescription of described label is as follows:
Preferably, the prescription of label of the present invention is as follows:
Another object of the present invention is to provide a kind of preparation method of cefprozil tablet, the method comprises the steps:
(1) cefprozil, cellulose milk sugar complex, cross-linking sodium carboxymethyl cellulose, magnesium stearate are sieved respectively, for subsequent use.
(2) get satisfactory cefprozil, cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mix homogeneously to the mixer.
(3) magnesium stearate is joined mix homogeneously in the product that step (2) obtains, tabletting.
(4) tablet that step (3) is made coating to the coating pan, and get final product.
(5) use aluminium foil or Aluminum-plastic composite bag etc. every material and container wet, lucifuge cefprozil tablet to be packed.
In the above-mentioned preparation method: cefprozil 80 orders; Cellulose-lactose 60 orders; Cross-linking sodium carboxymethyl cellulose 100 orders; Magnesium stearate 100 orders.
In the above-mentioned preparation method, the incorporation time in the step (3) is 20 minutes, the condition lower sheeting of 18～26 ℃ of tabletting ambient temperatures, humidity 45～65%, and tabletting pressure is controlled at 30～35kN, and the tablet machine rotating speed is controlled at 10000～15000 slices/hour.
Environmental condition may cause direct impact to tabletting, when air humidity was too high, the phenomenon that sticking appears in the more intense drug particles of hygroscopicity medicine was very obvious, and the inventor finds through a large amount of tests, when 15～30 ℃ of ambient temperatures, during the condition lower sheeting of relative humidity 40～70%, the good moldability of tablet of the present invention, unilateral bright and clean, the sticking phenomenon does not appear, preferably, 18～26 ℃ of ambient temperatures, humidity is controlled at 45～65%.When tabletting pressure was excessive, the hardness of tablet was excessive, caused the prolonged disintegration of tablet, pressure too hour, tablet hardness is too small, tablet is easy-formation not, the pressure controlled 25～40kN of tabletting of the present invention, preferred 30～35kN.10000～15000 slices/hour of preferred tablet machine rotating speeds.
Preferably, the preparation method of cefprozil tablet of the present invention comprises the steps:
(1) cefprozil is crossed 80 mesh sieves, cellulose milk sugar complex and crossed 60 mesh sieves, cross-linking sodium carboxymethyl cellulose, magnesium stearate and cross respectively 100 mesh sieves, for subsequent use.
(2) get satisfactory cefprozil, cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mix homogeneously to the mixer.
(3) magnesium stearate is joined mix homogeneously in the product that step (2) obtains, measures drug content, determine sheet heavy after at the condition lower sheeting of 18～26 ℃ of ambient temperatures, humidity 45～65%, tabletting pressure 30～35kN.
(4) tablet that step (3) is made coating to the coating pan, and get final product.
(5) use aluminium foil or Aluminum-plastic composite bag etc. every material and container wet, lucifuge cefprozil tablet to be packed.
The used coating solution prescription of the present invention is the solution that OPADRY and 90% ethanol form.
Prescription of the present invention obtains through screening, and screening process is as follows:
The screening of filler
In the present invention, flow is good three kinds of adjuvant microcrystalline cellulose excipients, spray-dried lactose, cellulose-lactose complex screen.Measure hardness, friability, the dissolution of angle of repose, the degree of compression and the tablet of the powder of respectively filling a prescription.The results are shown in Table 1.
The different types of diluent of table 1 is on the impact of powder and tablet quality
The result shows that flowability, the compressibility of cellulose-lactose complex all are better than single adjuvant or the simple adjuvant that mixes, increase along with cellulose-lactose consumption, the flowability of powder improves, the hardness of tablet increases, consider the character of powder and the character of tablet, determine that cellulose-lactose complex is as filler.
The screening of binding agent
The ratio of anchoring fiber element-lactose complex, lubricant adds respectively the PVP K30 of 1%, 2%, 3% consumption in the prescription, investigate the consumption of PVP K30 to the impact of powder and tablet quality.The results are shown in Table 2.
Table 2 PVP K30 is on the impact of powder and tablet quality
The result shows and adds PVP K30 in the prescription, the mobile variation of powder, and the dissolution of tablet, friability are without significant change, and hardness increases.Because not adding the existing enough hardness of tablet that the binding agent polyvidone produces in the prescription, and the friability of tablet with dissolution with respect to the tablet that adds poly-dimension K30 without obvious difference, so remove not add PVP K30 in determining to fill a prescription.
The screening of disintegrating agent
Select cross-linking sodium carboxymethyl cellulose (CMC-Na), low-substituted hydroxypropyl cellulose (L-HPC), three kinds of disintegrating agents of carboxymethyl starch sodium (CMS-Na) to add in the prescription according to same amount respectively, investigate different types of disintegrating agent to the impact of powder and tablet quality.The results are shown in Table 3.
Table 3 disintegrating agent is on the impact of powder and tablet quality
Experimental result shows that three kinds of identical different disintegrating agents of consumption compare, the tablet hardness that is pressed into and friability are without significant difference, but the dissolution of the plain sheet of the flowability of the powder of adding cross-linking sodium carboxymethyl cellulose and compressibility, compacting all is better than other two kinds of disintegrating agents, so select cross-linking sodium carboxymethyl cellulose as the disintegrating agent of this product.
The orthogonal design optimization of C/C composites
Investigate the result according to single factor, selecting cellulose-lactose complex consumption, disintegrating agent (CMC-Na) consumption, three parameters of magnesium stearate consumption is factor, determines respectively three levels.See Table 4.
Table 4 factor level table
Use L9 (33) orthogonal table experiment arrangement, the coating conditions and the production practical experience that whether are fit to next step according to compressed tablet, formulate the comprehensive grading method: poor fluidity (angle of repose is greater than 40 degree) is 0 minute, preferably (angle of reposes 35～40 degree) 1 minute, good (angle of repose is less than 35 degree) are 2 minutes; Hardness (N):＜50N is 0 minute, and 51～80N is 1 minute, and＞81N is 2 minutes; Disintegration time (s):＞60 is 0 minute; 30～60 is 1 minute;＜30 is 2 minutes.Experimental design and the results are shown in Table 5.
Table 5 orthogonal experiment scheme and result
The result shows that the optimal proportion of each factor is A2B2C2.Be that cellulose-lactose complex accounts for 35%, cross-linked carboxymethyl cellulose sodium accounts for 3%, and magnesium stearate accounts for 0.7%.
Compared with prior art, the present invention has following advantage:
(1) Dissolution of Tablet of the present invention is good;
(2) good stability of cefprozil tablet of the present invention;
(3) in the preparation method of the present invention, first with cefprozil and cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mix homogeneously, again with magnesium stearate and above-mentioned powder mixing, tabletting, coating, the tablet stripping that makes with this method is good, good stability, beta-lactam nucleus open loop less degradation.
The specific embodiment
Below be the specific embodiment of the present invention, described embodiment is in order to further describe the present invention, rather than restriction the present invention.
Embodiment 1
(1) prescription:
The label prescription:
Coating solution prescription: 1000 consumptions
Opadry coating powder 12.3g
90% ethanol adds to 205ml
(2) preparation method:
(1) cefprozil is crossed 80 mesh sieves, cellulose milk sugar complex and crossed 60 mesh sieves, cross-linking sodium carboxymethyl cellulose, magnesium stearate and cross respectively 100 mesh sieves, for subsequent use.
(2) getting satisfactory cefprozil, cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mixed 20 minutes to mixer.
(3) magnesium stearate is joined mix homogeneously in the product that step (2) obtains, measures drug content, determine sheet heavy after at the condition lower sheeting of 18 ℃ of ambient temperatures, humidity 45%, tabletting pressure 30～35kN.
(4) tablet that step (3) is made coating to the coating pan, and get final product.
(5) use aluminium foil or Aluminum-plastic composite bag etc. every material and container wet, lucifuge cefprozil tablet to be packed.
Embodiment 2
(1) prescription:
The label prescription:
Coating solution prescription: 1000 consumptions
Opadry coating powder 12.3g
90% ethanol adds to 205ml
(2) preparation method:
(1) cefprozil is crossed 80 mesh sieves, cellulose milk sugar complex and crossed 60 mesh sieves, cross-linking sodium carboxymethyl cellulose, magnesium stearate and cross respectively 100 mesh sieves, for subsequent use.
(2) get satisfactory cefprozil, cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mix homogeneously to the mixer.
(3) magnesium stearate is joined mix homogeneously in the product that step (2) obtains, measures drug content, determine sheet heavy after at the condition lower sheeting of 18 ℃ of ambient temperatures, humidity 60%, tabletting pressure 30～35kN.
(4) tablet that step (3) is made coating to the coating pan, and get final product.
(5) use aluminium foil or Aluminum-plastic composite bag etc. every material and container wet, lucifuge cefprozil tablet to be packed.
Embodiment 3
(1) prescription:
The label prescription:
Coating solution prescription: 1000 consumptions
Opadry coating powder 12.3g
90% ethanol adds to 205ml
(2) preparation method:
(1) cefprozil is crossed 80 mesh sieves, cellulose milk sugar complex and crossed 60 mesh sieves, cross-linking sodium carboxymethyl cellulose, magnesium stearate and cross respectively 100 mesh sieves, for subsequent use.
(2) get satisfactory cefprozil, cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mix homogeneously to the mixer.
(3) magnesium stearate is joined mix homogeneously in the product that step (2) obtains, measures drug content, determine sheet heavy after at the condition lower sheeting of 26 ℃ of ambient temperatures, 60 ℃ of humidity, tabletting pressure 30～35kN.
(4) tablet that step (3) is made coating to the coating pan, and get final product.
(5) use aluminium foil or Aluminum-plastic composite bag etc. every material and container wet, lucifuge cefprozil tablet to be packed.
The stability comparative test
According to a collection of product of example 2 preparations of the present invention and a commercially available batch sample, be respectively A and B, according to " 2010 editions two appendix XIXC of Chinese pharmacopoeia carry out influence factor's test and stability test.
(1) exposure experiments to light
At ambient temperature, will make by oneself after sample and commercially available product remove packing respectively, it was to place 10 days under the condition of 4500Lx ± 500Lx that opening places illumination, respectively at 0,5,10 day regularly sampling, simultaneously character, content, dissolution and the related substance of test sample.The result and with compared in 0 day, investigate the variation of indices.The results are shown in Table 6.
Table 6 cefprozil tablet exposure experiments to light is investigated the result
As can be seen from Table 1, self-control sample and commercially available product, are compared with 0 day testing result after 10 days through strong illumination, and the character of sample, dissolution are all without significant change; Related substance slightly increases; Content slightly has reduction.But indices is still up to specification.From the above results as can be known, illumination is slightly influential to this product, and this product should keep in Dark Place.
(2) hot test
To make by oneself after sample and commercially available product remove packing respectively, opening was placed 10 days under 60 ℃ condition, respectively at 0,5,10 day regularly sampling, simultaneously character, content, dissolution and the related substance of test sample.The result and with compared in 0 day, investigate the variation of indices.The results are shown in Table 7.
The result is investigated in the hot test of table 7 cefprozil tablet
As can be seen from Table 2, by the result as can be known, self-control sample and commercially available product are compared with 0 day testing result after placing 10 days under the hot conditions, and the character of sample, dissolution, content are all without significant change, and only related substance slightly increases, but still up to specification.From the above results as can be known, high temperature can make the related substance of this product increase, so this product should be preserved (being no more than 20 ℃) in the cool.
(3) high wet test
To make by oneself after sample and commercially available product remove packing respectively, opening places the constant humidity hermetic container of relative humidity 90% ± 5%, places 10 days in 25 ℃, respectively at 0,5,10 day regularly sampling, simultaneously test sample related index.And compare with 0 day testing result.Test sample weight before and after accurately weighing is tested simultaneously is to investigate the moisture absorption deliquescence performance of test sample.The results are shown in Table 8.
The high wet test of table 8 cefprozil tablet is investigated result's (RH=90% ± 5%)
As can be seen from Table 3, self-control sample and commercially available product compare with 0 day testing result after relative humidity (90% ± 5%) is placed 10 days.The character of sample, dissolution, content are all without significant change, and only related substance slightly increases.The material that the moisture absorption of sample weightening finish results suggest cefprozil tablet need select to have good humidity resistance is packed and is placed dry place to preserve, and can more effectively prevent the sample moisture absorption.
(4) accelerated test
To make respectively three batch samples (090901 by oneself, 090902,090903 batch), the simulation commercially available back, place the medicine stability experimental box of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5% to place 6 months, in 0,1,2,3,6 the end of month timing sampling, according to cefprozil tablet quality standard draft, above-mentioned investigation project is detected.The results are shown in Table 9.
Table 9 accelerated test result
As can be seen from Table 4, cefprozil tablet simulation commercially available back is 40 ℃ ± 2 ℃ of temperature, place after 6 months under the condition of relative humidity 75% ± 5%, as stated above indices is detected, the result shows, indices and comparison in 0 day have no significant change.As seen, this product is pressed commercially available back, places in 6 months stable under acceleration environment.
(5) long term test
To make respectively test agent in three batches (090901,090902,090903 batch) by oneself, the simulation commercially available back places 25 ℃ ± 2 ℃ of temperature, places 24 months under the condition of relative humidity 60% ± 10%, reserved sample observing is in 0,3,6,9,12,18,24 the end of month timing sampling, according to cefprozil tablet quality standard draft, above-mentioned investigation project is detected.The results are shown in Table 10.
Table 10 long-term test results
As can be seen from Table 5, cefprozil tablet simulation commercially available back is 25 ℃ ± 2 ℃ of temperature, place after 18 months under the condition of relative humidity 60% ± 10%, as stated above indices is detected, the result shows, indices and comparison in 0 day have no significant change.As seen, this product is placed in 18 months stable by the listing packing at ambient temperature.
Claims (6)
1. a cefprozil tablet comprises label and film-coat layer, and wherein the prescription of label is: 61.3 parts of cefprozils, 35.0 parts of celluloses-lactose complex, 3 parts of cross-linking sodium carboxymethyl celluloses, 0.7 part of magnesium stearate; The preparation method of this cefprozil tablet is as follows:
(1) cefprozil, cellulose milk sugar complex, cross-linking sodium carboxymethyl cellulose, magnesium stearate are sieved respectively, for subsequent use,
(2) get satisfactory cefprozil, cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mix homogeneously to the mixer,
(3) magnesium stearate is joined mix homogeneously in the product that step (2) obtains, tabletting,
(4) tablet that step (3) is made coating to the coating pan, and get final product,
(5) use aluminium foil or Aluminum-plastic composite bag every material and container wet, lucifuge cefprozil tablet to be packed.
2. cefprozil tablet as claimed in claim 1, it is characterized in that: the granularity requirements of described each component is cefprozil 80 orders; Cellulose-lactose complex 60 orders; Cross-linking sodium carboxymethyl cellulose 100 orders; Magnesium stearate 100 orders, the bulk density of described cefprozil are 0.48～0.52g/ml, and the bulk density of cellulose-lactose complex is 0.37～0.42g/ml.
3. cefprozil tablet, the prescription of making 1000 is as follows: wherein the label prescription is: cefprozil 250.0g, cellulose-lactose complex 142.7g, cross-linking sodium carboxymethyl cellulose 12.2g, magnesium stearate 2.9g, wherein the coating solution prescription is: Opadry coating powder 12.3g, and 90% ethanol adds to 205ml; The preparation method of this cefprozil tablet is as follows:
(1) cefprozil is crossed 80 mesh sieves, cellulose milk sugar complex and crossed 60 mesh sieves, cross-linking sodium carboxymethyl cellulose, magnesium stearate and cross respectively 100 mesh sieves, for subsequent use;
(2) get satisfactory cefprozil, cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mix homogeneously to the mixer;
(3) magnesium stearate is joined mix homogeneously in the product that step (2) obtains, measures drug content, determine sheet heavy after at the condition lower sheeting of 18 ℃ of ambient temperatures, humidity 60%, tabletting pressure 30～35kN;
(4) tablet that step (3) is made coating to the coating pan, and get final product;
(5) use aluminium foil or Aluminum-plastic composite bag every material and container wet, lucifuge cefprozil tablet to be packed.
4. cefprozil tablet as claimed in claim 1, it is characterized in that, wherein the incorporation time in the step (3) is 15～25 minutes, 15～30 ℃ of tabletting ambient temperatures, the condition lower sheeting of humidity 40～70%, tabletting pressure is controlled at 25～40kN, and the tablet machine rotating speed is controlled at 10000～15000 slices/hour.
5. cefprozil tablet as claimed in claim 1 is characterized in that, described preparation method is as follows:
(1) cefprozil is crossed 80 mesh sieves, cellulose milk sugar complex and crossed 60 mesh sieves, cross-linking sodium carboxymethyl cellulose, magnesium stearate and cross respectively 100 mesh sieves, for subsequent use,
(2) get satisfactory cefprozil, cellulose-lactose complex, cross-linking sodium carboxymethyl cellulose mix homogeneously to the mixer,
(3) magnesium stearate is joined in the product that step (2) obtains and mixed 15～25 minutes, measure drug content, determine sheet heavy after at the condition lower sheeting of 15～30 ℃ of ambient temperatures, humidity 40～70%, tabletting pressure 25～40kN,
(4) tablet that step (3) is made coating to the coating pan, and get final product,
(5) use aluminium foil or Aluminum-plastic composite bag every material and container wet, lucifuge cefprozil tablet to be packed.
6. cefprozil tablet as claimed in claim 5 is characterized in that wherein the incorporation time in the step (3) is 20 minutes, 18～26 ℃ of tabletting ambient temperatures, and the condition lower sheeting of humidity 45～65%, tabletting pressure is controlled at 30～35kN.
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| CN103417509B (en) * | 2013-08-15 | 2015-04-29 | 华北制药河北华民药业有限责任公司 | Cefprozil tablet and preparation method thereof |
| CN104398484B (en) * | 2014-12-04 | 2017-11-24 | 石家庄四药有限公司 | Rosuvastatin calcium tablets and preparation method thereof |
| CN104473892B (en) * | 2014-12-25 | 2017-08-15 | 辰欣药业股份有限公司 | It is a kind of for faropenem composition of sodium of direct tablet compressing and preparation method thereof |
| CN105125512B (en) * | 2015-09-09 | 2018-04-17 | 山东大学 | A kind of crystalline substance V-type Puerarin tablet and preparation method thereof |
| CN110151721B (en) * | 2019-06-10 | 2021-11-12 | 乐普制药科技有限公司 | Atorvastatin calcium-containing tablet and preparation method thereof |
| CN110327305A (en) * | 2019-06-26 | 2019-10-15 | 慧生医学科技(徐州)有限公司 | A kind of ticagrelor piece and preparation method thereof |
| CN116157391A (en) * | 2020-11-11 | 2023-05-23 | 上海海雁医药科技有限公司 | Pharmaceutical composition comprising EGFR inhibitor and preparation method thereof |
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