CN102247331B - Cefadroxil chewable tablets and preparation method thereof - Google Patents
Cefadroxil chewable tablets and preparation method thereof Download PDFInfo
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- CN102247331B CN102247331B CN2010102448175A CN201010244817A CN102247331B CN 102247331 B CN102247331 B CN 102247331B CN 2010102448175 A CN2010102448175 A CN 2010102448175A CN 201010244817 A CN201010244817 A CN 201010244817A CN 102247331 B CN102247331 B CN 102247331B
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Abstract
The invention relates to cefadroxil chewable tablets and a preparation method thereof. The cefadroxil chewable tablets provided by the invention comprise the following raw material components in parts by weight: 110-550 parts of cefadroxil, 240-1,050 parts of mannitol, 110-500 parts of sucrose, 15-90 parts of maltodextrin, 0.5-5 parts of aspartame, 10-70 parts of sweet orange powder essence, 0.5-5 parts of menthol, a proper amount of water and 3-25 parts of magnesium stearate. The cefadroxil chewable tablets provided by the invention have high absorption speed, no lingering bitterness and excellent mouthfeel.
Description
Technical field
The present invention relates to a kind of cefadroxil chewable tablet and preparation method thereof, belong to field of pharmaceutical technology.
Background technology
Cefadroxil is a kind of semisynthetic orally active cephalo-type broad spectrum antibiotic, belongs to first generation cephalosporin, is used to treat bacterial infection disease clinically.It all has bactericidal action to Gram-positive, negative bacterium, compares with other oral cephalosporins medicines, and its extracorporeal disinfecting effect is more remarkable.Although existing at present second, third, the 4th generation cephalosporin occur because its oral absorption is good, dosage form is many, persistent, good effect, so still widely-used clinically.
Cefadroxil is all carrying out with slower speed aspect absorption and the urinary tract drainage, makes it aspect pharmacokinetics, be different from other oral cephalosporins at present.Therefore, it can keep effective Mlc of long period in vivo.The oral absorption of cefadroxil is good, can be directly oral, need not do irritated skin test, convenient oral; Rate of side effects is low, long half time, twice on the one; Do not receive food effect in the stomach, clinical compliance is good, and clinical trial shows that it has good tolerability; Moderate is gently arrived in untoward reaction, and is detected in the patient who often accepts the cephalosporin treatment, shows as gastrointestinal upset and anaphylaxis.In view of above various advantages, cefadroxil sustainable growth in clinical use.In addition, the cefadroxil convenient oral is adapted to urinary tract, biliary tract, and infection such as respiratory tract, and indication is extensive, and is safe, welcome by the patient.And along with development of technology, the cost of material of cefadroxil also will continue to reduce, and the preparation cost also will be along with reduction, so the development prospect of cefadroxil preparation is very bright.
The dosage form of the cefadroxil of clinical practice at present has only tablet, capsule and granule.Because cefadroxil has and is slightly soluble in water, oral absorption speed and slowly causes short defective of Mlc time in the body, and tablet has one specificity little smelly, makes the people produce uncomfortable sensation.Therefore be badly in need of the more advanced dosage form of exploitation, to overcome this defective.
Application number is that 200410007545.1 one Chinese patent application discloses a kind of cefadroxil oral cavity disintegration tablet and preparation method thereof; Comprising the cefadroxil of effective dose with can be in the oral cavity rapidly disintegrate discharge the pharmaceutical excipient of medicine; Pharmaceutical excipient is water-soluble filler, disintegrating agent, lubricant, wetting agent or binding agent; This disintegration of tablet is rapid, and is rapid-action; Intestinal is residual little, absorbs fully, and side effect is low; Medication is convenient, and mouthfeel is good.
Application number is that 200510012375.0 one Chinese patent application discloses a kind of cefadroxil dry suspension and method for preparing, belongs to medical technical field, is used to solve the problem that improves cefadroxil water solublity and bioavailability.It is made up of principal agent cefadroxil and adjuvant, and the content of unit meter in the prescription total amount is following by weight for each main materials and auxiliary materials: cefadroxil 80-120, inclusion agents 16-60; Water-soluble filler 440-520; Disintegrating agent 55-70, suspending agent 5-10, binding agent 30-45.Characteristics such as it is high that product of the present invention has drug solubility and bioavailability, and chemical stability is good, and mouthfeel is good, taking convenience, patient's compliance are strong.The present invention processes the dry suspension type, can be in gastrointestinal tract extensively distributes, and absorption point increases, and absorbs more fully, and has reduced medicine to the gastrointestinal local excitation.
Chewable tablet is one type can chew the tablet under the posterior phraynx in the oral cavity, size is general identical with conventional tablet, can process difform special-shaped sheet as required.Tablet is convenient to swallow after chewing, and the tablet surface area increases, and can promote medicine dissolving, absorption in vivo.For the not good medicine of absorbability, process chewable tablet and can quicken its disintegrate, promote the drug absorption availability.The chewable tablet taking convenience even also medication on time under the condition of hydropenia is specially adapted to the relatively poor patient of children's, old man, dysphagia or gastrointestinal function, can reduces medicine gastrointestinal is born.Therefore, chewable tablet is used extensively to get up gradually.
" the human-body biological equivalence of cefadroxil chewable tablet " [referring to Deng Ming etc. the human-body biological equivalence of cefadroxil chewable tablet. the Chinese Hospitals pharmaceutical journal; 2007; 27 (4): 461-463] estimated cefadroxil chewable tablet and reference tablet bioequivalence in human body, the result shows that two preparations have bioequivalence.
Though above-mentioned document has been mentioned a kind of cefadroxil chewable tablet; But because the plain sheet of cefadroxil has one specificity stink; Make the people produce uncomfortable sensation; How effectively mask malodors is with the drug compliance of guaranteeing the patient, guarantee that drug effect is equal to or is superior to existing preparation simultaneously, and above-mentioned document does not provide more instruction or enlightenment, and from above-mentioned document, can not get the adjuvant of any relevant suitable cefadroxil chewable tablet and the teachings of consumption thereof yet.
In view of this, special proposition the present invention.
Summary of the invention
The object of the present invention is to provide a kind of cefadroxil chewable tablet, cefadroxil is added suitable adjuvant be prepared into chewable tablet, solved cefadroxil and had little smelly, the patient of specificity and be reluctant oral problem; Directly process chewable tablet, good, the taking convenience of mouthfeel not only, and can reach the effect of treatment bacterial infection rapidly; Improved chewable tablet quality stability, medicine is through chewing, and its effective ingredient oral mucosa absorbs rapidly; Absorb fast; Bioavailability is high, and is evident in efficacy, to solve the problem that exists in the prior art.
Another object of the present invention is to provide a kind of method for preparing of cefadroxil chewable tablet, this method is simple, and prepared chewable tablet infiltration rate is fast, bitterness without issue, taste good.
For realizing first purpose of the present invention, the present invention adopts following technical scheme:
A kind of cefadroxil chewable tablet, wherein, described chewable tablet comprises following raw material components:
Cefadroxil 110-550 weight portion
Mannitol 240-1050 weight portion
Sucrose 110-500 weight portion
Maltodextrin 15-90 weight portion
Aspartame 0.5-5 weight portion
Fructus Citri sinensis powdered flavor 10-70 weight portion
Mentholum 0.5-5 weight portion
Water is an amount of
Magnesium stearate 3-25 weight portion.
Preferably, described chewable tablet comprises following raw material components:
Cefadroxil 132 weight portions
Mannitol 250 weight portions
Sucrose 123 weight portions
Maltodextrin 22 weight portions
Aspartame 1 weight portion
Fructus Citri sinensis powdered flavor 15 weight portions
Mentholum 1 weight portion
Water is an amount of
Magnesium stearate 5.5 weight portions.
Perhaps, described chewable tablet comprises following raw material components:
Cefadroxil 264 weight portions
Mannitol 500 weight portions
Sucrose 246 weight portions
Maltodextrin 44 weight portions
Aspartame 2 weight portions
Fructus Citri sinensis powdered flavor 30 weight portions
Mentholum 2 weight portions
Water is an amount of
Magnesium stearate 11 weight portions.
Perhaps, described chewable tablet comprises following raw material components:
Cefadroxil 528 weight portions
Mannitol 240 weight portions
Sucrose 130 weight portions
Maltodextrin 88 weight portions
Aspartame 4 weight portions
Fructus Citri sinensis powdered flavor 60 weight portions
Mentholum 4 weight portions
Water is an amount of
Magnesium stearate 11 weight portions.
Wherein said cefadroxil 132 weight portions are equivalent to cefadroxil anhydride 125 weight portions.
For realizing second purpose of the present invention, the present invention adopts following technical scheme:
A kind of method for preparing of cefadroxil chewable tablet of the present invention, wherein, this method comprises the steps:
1) respectively with cefadroxil, mannitol, maltodextrin, sucrose, aspartame and Mentholum crushing screening;
2) will spray into water again and granulate through cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and the Fructus Citri sinensis powdered flavor mix homogeneously of crushing screening of last step, drying obtains dried particles;
3) add magnesium stearate in the dried particles that upwards step obtains, mix homogeneously, tabletting promptly gets.
According to the method for preparing of aforesaid cefadroxil, wherein, the cefadroxil described in the step 1) was 100 mesh sieves; Described mannitol, maltodextrin, sucrose, aspartame and Mentholum were 80 mesh sieves.
According to the method for preparing of aforesaid cefadroxil, wherein, described step 2) mixing described in is blended in a step comminutor, and the mixing in the step 3) is blended in dry-mixed machine.
According to the method for preparing of aforesaid cefadroxil, wherein, rotating speed 30～70r/min when in comminutor, mixing, preferred 50～70r/min mixes 5～20min, preferred 5～10min; Rotating speed 5～50r/min mixes 20～30min when in dry-mixed machine, mixing.
According to the method for preparing of aforesaid cefadroxil, wherein, said preparation process is under ambient temperature 18-26 ℃, the condition of envionmental humidity 45%-65%, to carry out.
According to the method for preparing of aforesaid cefadroxil, wherein, described drying is to be dried to moisture 3%-6%.
Below be detailed description of the present invention:
One aspect of the present invention provides a kind of cefadroxil chewable tablet, and this chewable tablet infiltration rate is fast, bitterness without issue, taste good.
Cefadroxil chewable tablet provided by the present invention comprises following raw material components: an amount of and magnesium stearate 3-25 weight portion of cefadroxil 110-550 weight portion, mannitol 240-1050 weight portion, sucrose 110-500 weight portion, maltodextrin 15-90 weight portion, aspartame 0.5-5 weight portion, Fructus Citri sinensis powdered flavor 10-70 weight portion, Mentholum 0.5-5 weight portion, water.
Chewable tablet must have good mouthfeel, and therefore, topmost problem is the selection of correctives in its preparation process.The chewable tablet that only has good taste just is prone to accepted by the patient, and most ingredient mouthfeel is relatively poor.Chewable tablet in buccal absorption should be selected bland correctives for use, to reduce the secretion of saliva.Swallow because of salivation can cause, too much swallow the buccal absorption that can reduce medicine; Not at the chewable tablet of buccal absorption, generally select sweet taste or have a little the correctives of tart flavour, should give feel cool after chewing, and meet saliva and can dissolve rapidly.The present invention selects the stronger aspartame of sweet taste for use, and the high 150-200 of its sweetness ratio sucrose times, and bitterness without issue, be difficult for causing dental caries, can also effectively reduce heat, therefore be suitable for diabetes and obesity patient.
The dosage form of cefadroxil domestic-developed is main with conventional dosage forms, and it is main being generally tablet, capsule, granule, the oral cavity chew or the dosage form of directly disintegrate seldom.Though chewable tablet has special value, especially aspect children because of the advantage that itself inherent characteristic and conventional tablet do not possess in clinical application.But all the time; Because cefadroxil has the specificity stink; Make the people produce uncomfortable sensation; How effectively mask malodors is with the drug compliance of guaranteeing the patient, guarantee that drug effect is equal to or is superior to existing preparation simultaneously; " though the human-body biological equivalence of cefadroxil chewable tablet " [referring to Deng Ming etc. the human-body biological equivalence of cefadroxil chewable tablet. Chinese Hospitals pharmaceutical journal, 2007,27 (4): 461-463] mentioned a kind of cefadroxil chewable tablet; But do not provide any teachings or instruction for the problems referred to above, and from above-mentioned document, can not get the adjuvant of any relevant suitable cefadroxil chewable tablet and the enlightenment or the instruction of consumption thereof.
Along with growth in the living standard, improve the compliance of patient's medication, and make things convenient for reason such as clinical application, the inventor develops good, the evident in efficacy cefadroxil chewable tablet of mouthfeel, thereby has accomplished the present invention through a large amount of prescription screening tests.
The inventor finds that through further test cefadroxil chewable tablet of the present invention preferably includes following raw material components: cefadroxil 132 weight portions, mannitol 250 weight portions, sucrose 123 weight portions, maltodextrin 22 weight portions, aspartame 1 weight portion, Fructus Citri sinensis powdered flavor 15 weight portions, Mentholum 1 weight portion, water is an amount of and magnesium stearate 5.5 weight portions.Wherein said cefadroxil 132 weight portions are equivalent to cefadroxil anhydride 125 weight portions.
Perhaps, described chewable tablet preferably includes following raw material components: an amount of and magnesium stearate 11 weight portions of cefadroxil 264 weight portions, mannitol 500 weight portions, sucrose 246 weight portions, maltodextrin 44 weight portions, aspartame 2 weight portions, Fructus Citri sinensis powdered flavor 30 weight portions, Mentholum 2 weight portions, water.
Perhaps, described chewable tablet preferably includes following raw material components: an amount of and magnesium stearate 11 weight portions of cefadroxil 528 weight portions, mannitol 240 weight portions, sucrose 130 weight portions, maltodextrin 88 weight portions, aspartame 4 weight portions, Fructus Citri sinensis powdered flavor 60 weight portions, Mentholum 4 weight portions, water.
The inventor is through further research; Find to adopt the cefadroxil chewable tablet of component preparation provided by the present invention to compare with the cefadroxil ordinary tablet pleasantly surprisedly; Have and absorb fast, bioavailability advantages of higher, and, find more pleasantly surprisedly through Test Example; Compare with cefadroxil chewable tablet of the prior art, cefadroxil chewable tablet curative effect of the present invention is more remarkable.
The present invention provides the method for preparing of cefadroxil chewable tablet of the present invention on the other hand, and is simple, and prepared chewable tablet infiltration rate is fast, bitterness without issue, taste good.
The method for preparing of cefadroxil chewable tablet provided by the present invention comprises the steps:
1) respectively with cefadroxil, mannitol, maltodextrin, sucrose, aspartame and Mentholum crushing screening;
2) will spray into water again and granulate through cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and the Fructus Citri sinensis powdered flavor mix homogeneously of crushing screening of last step, drying obtains dried particles;
3) add magnesium stearate in the dried particles that upwards step obtains, mix homogeneously, tabletting promptly gets.
In the method for preparing of cefadroxil provided by the present invention, wherein, the cefadroxil described in the step 1) was 100 mesh sieves; Described mannitol, maltodextrin, sucrose, aspartame and Mentholum were 80 mesh sieves.
In the method for preparing of cefadroxil provided by the present invention, wherein, described step 2) mixing described in is blended in a step comminutor, and the mixing in the step 3) is blended in dry-mixed machine.
In the method for preparing of cefadroxil provided by the present invention, wherein, rotating speed 30～70r/min when in comminutor, mixing, preferred 50～70r/min mixes 5～20min, preferred 5～10min; Rotating speed 5～50r/min mixes 20～30min when in dry-mixed machine, mixing.
In the method for preparing of cefadroxil provided by the present invention, wherein, said preparation process is under ambient temperature 18-26 ℃, the condition of envionmental humidity 45%-65%, to carry out.
In the method for preparing of cefadroxil provided by the present invention, wherein, described drying is to be dried to moisture 3%-6%.
Compared with prior art, the present invention has following advantage:
(1) onset is rapid: chewable tablet both can have been sucked also can chew clothes, when being used to treat upper respiratory tract infection, sucking administration and can directly act on upper respiratory tract, and local concentration is high, and rapid-action, curative effect is better.If be used to treat urinary system or skin infection, take after can chewing, compare with conventional tablet or capsule, shortened dissolution time, make medicine can bring into play the whole body therapeutic effect rapidly;
(2) high, the good effect of bioavailability: test shows that cefadroxil chewable tablet of the present invention is high than cefadroxil ordinary tablet bioavailability, good effect;
(3) medication is convenient: need not use mixing in water for oral taking, can take whenever and wherever possible, for the child who goes to school or go up kindergarten provides great convenience, also can alleviate the trouble that the head of a family gives child's medicine feed, can receive the numerous heads of a family and child's welcome after estimating to go on the market;
(4) mouthfeel is excellent: this project has been used special coverage flavor technology in preparation process, has overcome the bad flavor of smelling of cefadroxil, and mouthfeel is fragrant and sweet, and refrigerant Herba Menthae and fruit abnormal smells from the patient are arranged, and can alleviate pharyngeal discomfort, and it is good that child patient is taken compliance.
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
Prepare burden 1000 (g)
Cefadroxil 132g (being equivalent to cefadroxil anhydride 125g)
Mannitol 250g
Sucrose 123g
Maltodextrin 22g
Aspartame 1g
Fructus Citri sinensis powdered flavor 15g
Mentholum 1g
Water is an amount of
Magnesium stearate 5.5g
(2) preparation technology
Take by weighing cefadroxil and mannitol, maltodextrin, sucrose, aspartame, Mentholum and the Fructus Citri sinensis powdered flavor through 80 mesh sieves through 100 mesh sieves; Put mix homogeneously in the step comminutor, spray into suitable quantity of water and granulate, weigh after the drying; Take by weighing 1% magnesium stearate; Add in the dry-mixed machine and dried particles mix homogeneously, the qualified back of semi-finished product content tabletting, the heavy 550mg of theoretical sheet.
Embodiment 2
(1) prescription
Prepare burden 1000 (g)
Cefadroxil 264g (being equivalent to cefadroxil anhydride 250g)
Mannitol 500g
Sucrose 246g
Maltodextrin 44g
Aspartame 2g
Fructus Citri sinensis powdered flavor 30g
Mentholum 2g
Water is an amount of
Magnesium stearate 11g
(2) preparation technology
1) respectively with cefadroxil, mannitol, maltodextrin, sucrose, aspartame and Mentholum crushing screening;
2) will spray into suitable quantity of water again and granulate through cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and the Fructus Citri sinensis powdered flavor mix homogeneously of crushing screening of last step, drying obtains dried particles;
3) add magnesium stearate in the dried particles that upwards step obtains, mix homogeneously, the qualified back of semi-finished product content tabletting promptly gets.
Embodiment 3
(1) prescription
Prepare burden 1000 (g)
Cefadroxil 528 weight portions
Mannitol 240 weight portions
Sucrose 130 weight portions
Maltodextrin 88 weight portions
Aspartame 4 weight portions
Fructus Citri sinensis powdered flavor 60 weight portions
Mentholum 4 weight portions
Water is an amount of
Magnesium stearate 11 weight portions.
(2) preparation technology
1) cefadroxil was pulverized 100 mesh sieves, mannitol, maltodextrin, sucrose, aspartame and Mentholum pulverize separately were crossed 80 mesh sieves;
2) by above-mentioned consumption take by weighing cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and Fructus Citri sinensis powdered flavor through crushing screening of last step in a step comminutor after rotating speed is to mix 20min under the condition of 30r/min mix homogeneously; Spray into suitable quantity of water again and granulate, be dried to moisture 3% and obtain dried particles;
3) magnesium stearate that adds above-mentioned consumption in the dried particles that upwards step obtains, in dry-mixed machine after mixing 30min under the condition of rotating speed 20r/min mix homogeneously, the qualified back of semi-finished product content tabletting promptly gets;
Said preparation process is under ambient temperature 18-26 ℃, the condition of envionmental humidity 45%-65%, to carry out.
Embodiment 4
(1) prescription
Prepare burden 1000 (g)
Cefadroxil 264g (being equivalent to cefadroxil anhydride 250g)
Mannitol 500g
Sucrose 246g
Maltodextrin 44g
Aspartame 2g
Fructus Citri sinensis powdered flavor 30g
Mentholum 2g
Water is an amount of
Magnesium stearate 11g
(2) preparation technology
1) cefadroxil was pulverized 100 mesh sieves, mannitol, maltodextrin, sucrose, aspartame and Mentholum pulverize separately were crossed 80 mesh sieves;
2) by above-mentioned consumption take by weighing cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and Fructus Citri sinensis powdered flavor through crushing screening of last step in a step comminutor after rotating speed is to mix 10min under the condition of 50r/min mix homogeneously; Spray into suitable quantity of water again and granulate, be dried to moisture 5% and obtain dried particles;
3) magnesium stearate that adds above-mentioned consumption in the dried particles that upwards step obtains, in dry-mixed machine after mixing 25min under the condition of rotating speed 30r/min mix homogeneously, the qualified back of semi-finished product content tabletting promptly gets;
Said preparation process is under ambient temperature 18-26 ℃, the condition of envionmental humidity 45%-65%, to carry out.
Embodiment 5
(1) prescription
Prepare burden 1000 (g)
Cefadroxil 132g (being equivalent to cefadroxil anhydride 125g)
Mannitol 250g
Sucrose 123g
Maltodextrin 22g
Aspartame 1g
Fructus Citri sinensis powdered flavor 15g
Mentholum 1g
Water is an amount of
Magnesium stearate 5.5g
(2) preparation technology
1) cefadroxil was pulverized 100 mesh sieves, mannitol, maltodextrin, sucrose, aspartame and Mentholum pulverize separately were crossed 80 mesh sieves;
2) by above-mentioned consumption take by weighing cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and Fructus Citri sinensis powdered flavor through crushing screening of last step in a step comminutor after rotating speed is to mix 5min under the condition of 70r/min mix homogeneously; Spray into suitable quantity of water again and granulate, be dried to moisture 6% and obtain dried particles;
3) magnesium stearate that adds above-mentioned consumption in the dried particles that upwards step obtains, in dry-mixed machine after mixing 20min under the condition of rotating speed 5r/min mix homogeneously, tabletting promptly gets;
Said preparation process is at ambient temperature 18-26 ℃, the condition lower sheeting of envionmental humidity 45%-65%, promptly gets.
Embodiment 6
(1) prescription
Prepare burden 1000 (g)
Cefadroxil 110g (being equivalent to cefadroxil anhydride 104g)
Mannitol 240g
Sucrose 110g
Maltodextrin 15g
Aspartame 0.5g
Fructus Citri sinensis powdered flavor 10g
Mentholum 0.5g
Water is an amount of
Magnesium stearate 3.0g
(2) preparation technology
1) cefadroxil was pulverized 100 mesh sieves, mannitol, maltodextrin, sucrose, aspartame and Mentholum pulverize separately were crossed 80 mesh sieves;
2) by above-mentioned consumption take by weighing cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and Fructus Citri sinensis powdered flavor through crushing screening of last step in a step comminutor after rotating speed is to mix 8min under the condition of 60r/min mix homogeneously; Spray into suitable quantity of water again and granulate, be dried to moisture 4% and obtain dried particles;
3) magnesium stearate that adds above-mentioned consumption in the dried particles that upwards step obtains, in dry-mixed machine after mixing 20min under the condition of rotating speed 15r/min mix homogeneously, tabletting promptly gets;
Said preparation process is under ambient temperature 18-26 ℃, the condition of envionmental humidity 45%-65%, to carry out.
Embodiment 7
(1) prescription
Prepare burden 1000 (g)
Cefadroxil 550g (being equivalent to cefadroxil anhydride 500g)
Mannitol 280g
Sucrose 500g
Maltodextrin 90g
Aspartame 5g
Fructus Citri sinensis powdered flavor 70g
Mentholum 5g
Water is an amount of
Magnesium stearate 12g
(2) preparation technology
1) cefadroxil was pulverized 100 mesh sieves, mannitol, maltodextrin, sucrose, aspartame and Mentholum pulverize separately were crossed 80 mesh sieves;
2) by above-mentioned consumption take by weighing cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and Fructus Citri sinensis powdered flavor through crushing screening of last step in a step comminutor after rotating speed is to mix 18min under the condition of 60r/min mix homogeneously; Spray into suitable quantity of water again and granulate, be dried to moisture 3% and obtain dried particles;
3) magnesium stearate that adds above-mentioned consumption in the dried particles that upwards step obtains, in dry-mixed machine after mixing 30min under the condition of rotating speed 20r/min mix homogeneously, tabletting promptly gets;
Said preparation process is under ambient temperature 18-26 ℃, the condition of envionmental humidity 45%-65%, to carry out.
Test Example 1
This Test Example is the prescription screening test.
1, the selection of filler adopts in dextrin, starch, microcrystalline Cellulose, mannitol or the sucrose one or both for filler respectively, is that index is carried out overall merit with mouthfeel, color and luster, formability, hardness, confirms filler.The result: gained tablet each item index is best when selecting mannitol and sucrose as filler, is filler so select mannitol and sucrose.See table 1.
Table 1, filler are to the influence of preparation process
(annotate: this item is selected in " √ " expression; "---" expression is not selected this.)
2, the selection chewable tablet of correctives need be chewed in mouth under the posterior phraynx, so taste is fine or not most important, is the adjustment mouthfeel; Confirm its taste with sweet be main; Have a little tart flavour, cooling feeling is arranged, adopt mannitol, xylitol, sorbitol, aspartame and Mentholum to make an experiment.With granulating process parameter (system soft material situation, soft material sieve situation) and tablet forming technique parameter (sticking situation, color and luster, hardness) and mouthfeel (tasty and refreshing) is leading indicator, carries out overall merit, confirms best correctives.
Considering the local flavor problem of chewable tablet simultaneously, adopt lactose, milk powder and orange juice as correctives, is that leading indicator is estimated with local flavor (get fed up, astringent taste, bitterness), and prescription is screened.The result can find out by aspartame and Mentholum gained tablet each item index best, so be correctives with aspartame and Mentholum.See table 2.
Table 2, different correctives are to the influence of preparation process and mouthfeel
(annotate: this item is selected in " √ " expression; "---" expression is not selected this.)
Adopting the Fructus Citri sinensis powdered flavor is that chewable tablet that correctives makes can not only well be covered the getting fed up of cefadroxil, astringent taste and bitterness, but also has given chewable tablet light orange fragrance, so selection Fructus Citri sinensis powdered flavor is as correctives.See table 3.
Table 3, correctives are to the influence of local flavor
Index lactose Fructus Citri sinensis powdered flavor acesulfame potassium orange juice
Get fed up and improve that the bigger improvement of less improvement is less does not almost have an improvement
Astringent taste improves that the bigger improvement of less improvement is less does not almost have an improvement
Bitterness improves that the bigger improvement of less improvement is less does not almost have an improvement
3, to adopt 5%HPMC, 75% ethanol and maltodextrin respectively be that binding agent is granulated in the selection of binding agent; With granulating process parameter (system soft material situation, soft material sieve situation) and tablet forming technique parameter (hardness) is index; Carry out overall merit, confirm the optimum adhesion agent.The result is that binding agent gained each item index is better with the maltodextrin, and granulating efficiency is good, so the employing maltodextrin is a binding agent.See table 4.
Table 4, different binding agent are to the influence of preparation process
Index 5%HPMC 75% ethanol maltodextrin
Soft material character situation is not agglomerating or not
The soft material situation of sieving is difficult for being prone to
Hardness about 3.0 about 2.5 about 4.0
Test Example 2
1, preparation process research
Wet granulation technology is adopted in this research, is binding agent with the maltodextrin, and the filler in the prescription has been carried out the prescription screening test.Through investigation to outward appearance, mouthfeel and the hardness of sample and the stability under high temperature and high humidity, confirm with mannitol, sucrose to be filler, and the optimum prescription has been carried out process certification, confirm prescription as follows:
1.1 prescription
Prepare burden 1000 (g)
Cefadroxil 132g (being equivalent to cefadroxil anhydride 125g)
Mannitol 250g
Sucrose 123g
Maltodextrin 22g
Aspartame 1g
Fructus Citri sinensis powdered flavor 15g
Mentholum 1g
Water is an amount of
Magnesium stearate 5.5g
1.2 preparation technology
Take by weighing cefadroxil and mannitol, maltodextrin, sucrose, aspartame, Mentholum and the Fructus Citri sinensis powdered flavor through 80 mesh sieves through 100 mesh sieves; Put mix homogeneously in the step comminutor, spray into suitable quantity of water and granulate, weigh after the drying; Take by weighing 1% magnesium stearate; Add in the dry-mixed machine and dried particles mix homogeneously, the qualified back of semi-finished product content tabletting, the heavy 550mg of theoretical sheet.
Test Example 3
This Test Example is the stability test of cefadroxil chewable tablet of the present invention.
1, related substance
The inventor was with reference to the relevant kind of version pharmacopeia in 2005; The related substance detection method of working out in the quality research process before perfect these article are clinical; Select for use impurity reference substance external standard method that these article known impurities 7-aminodesacetoxycephalosporanic acid reference substance, α-para hydroxybenzene glycosides propylhomoserin are checked; And stipulate that these two kinds of impurity and other maximum single impurity all must not cross 1.0%, other impurity summation must not cross 3.0%.
2, assay
In order to simplify the operation course, codes and standards, the inventor has changed the mobile phase system of assay, and has carried out methodological study again, evidence, the revision of doing does not influence the specificity and the accuracy of assay.
3, stability study
The present invention has proceeded long term test to three batches of pilot products, and has carried out investigating (this test proceeds to 36 months at present) to keeping sample by above-mentioned determination of related substances condition.In addition, also three batches of test samples of these article production unit quantity-produced (lot number: 050501,050502,050503 batch) have been carried out 36 months the test that keeps sample for a long time.
Content of the test: three batches of test samples (lot number: 050501,050502,050503 batch) of the embodiment of the invention 1 are placed climatic chamber by the listing packing; 25 ℃ ± 2 ℃ of temperature; The condition held of relative humidity 60% ± 10% 36 months detected by stable high spot reviews project respectively at 0 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months.Result of the test shows, pilot product is after 36 months long term tests, and character is basicly stable.Result of the test is following:
Pilot scale production sample long-term test results
Cefadroxil chewable tablet to other embodiment of the present invention has also carried out identical test, and the result of its acquisition is similar.
Test Example 4
This Test Example is cefadroxil of the present invention and the comparative test of ordinary tablet human bioavailability.
(1) experimenter selects:
Select health to be tried volunteer 10 people, tried to reach in the last week duration of test and do not take any other medicine, tried fasting in preceding 12 hours.
(2) sample:
A test specimen: the cefadroxil chewable tablet of the embodiment of the invention 1
The R control sample: the cefadroxil sheet (trade name: Ou Yi, specification: the 250mg/ sheet, lot number: 050603, Ou Yi Shi Pharmaceutical Group Pharmaceutical Co produces)
(3) method of testing:
Adopt two preparation binary cycle trial design, the experimenter is divided into 2 groups immediately by after the Body Mass Index ordering, 20 healthy male subjects by two preparation binary cycle trial design single oral dose 500mg reference preparation R with receive test preparation A, twice test cleaning phase is 7 days, take medicine get the blood time be h (hour): 0.25,0.5; 0.75,1,1.5,2,2.5; 3,4,6,8,10; From upper limb extracting vein blood 2ml, put in the anticoagulant heparin pipe and place 1h respectively, centrifuging and taking blood plasma is put-20 ℃ and is descended frozen, subsequent use.Plasma sample is handled: quantitatively gets blood plasma, adds 5% trichloroacetic acid, and vortex mixed 0.5min, the centrifuging and taking supernatant advances high-efficient liquid phase analysis in the 263nm place, measures human body blood drug level.See table:
(4) result of the test:
Obviously visible from the watch test data, cefadroxil chewable tablet of the present invention is within taking medicine back 0.5 hour, and the blood drug level C of human body is higher than ordinary tablet, explains that chewable tablet of the present invention is absorbed easily, has rapid-action characteristics.T
MaxTest through non-engaging in an inspection, receive test preparation and reference preparation that statistically-significant difference (P＜0.05) is arranged, receive the T of test preparation
MaxLess; C
Max, AUC
0-10h, AUC
0-∞After to number conversion, do variance analysis, receive test preparation and reference preparation all not to have statistically-significant difference (P＞0.05).Two-way one-side t assay shows and receives test preparation C
Max90% fiducial limit drop on reference preparation 70%～143% scope, receive 90% fiducial limit of test preparation AUC all to drop on reference preparation 80%～125% scope; With AUC
0-10hCalculate, receive the relative bioavailability of test preparation cefadroxil chewable tablet to be (99.0 ± 7.0) % (AUC
0-t, A/ AUC
0-t, R* 100%).The cefadroxil sheet degree of absorption that proves the production of chewable tablet of the present invention and Ou Yi Shi Pharmaceutical Group Pharmaceutical Co is suitable, and infiltration rate is very fast.
20 health volunteer's single oral dose 500mg reference preparations (R) and chewable tablet of the present invention (A)
The concentration of cefadroxil (ug/ml) sees the following form in the back blood plasma:
Cefadroxil chewable tablet to other embodiment of the present invention has also carried out identical test, and the result of its acquisition is similar.
Test Example 5
1, object
To obvious respiratory tract infection symptom was arranged between 3～April in 2010, on every Wendesdays, children's that six mornings, Zhuhai hospital outpatient was gone to a doctor is as the object of observation.Wednesday, prescription on individual diagnosis person was a matched group, and Saturday, prescription on individual diagnosis person was the treatment group.Medicament is known to have allergies or side reaction person not to make selected object to making.
1.1 22 examples are organized in treatment, male 11 examples, women 11 examples, 3.5 years old mean age (18 days～10 years old).Heating: body temperature＞38 ℃ 9 examples (40.90%),＞39 ℃ of 5 example (22.72%); Serious cough 17 examples (77.27%); Red swelling of the pharynx ++～+++18 examples (81.18%), pulmonary hears and rhonchi 6 examples (27.27%), pulmonary hears and a small amount of moist rale 2 examples (9.09%) of doing, 1 example (4.54%) except that the rhonchi prolonged expiration with wheezing sound; 22 examples are all done blood examination on every side and are tested, leukocyte≤10 * 10
9/ L6 example (27.27%), (10～20) * 10
9/ L15 example (68.18%),＞20 * 10
9/ L1 example (4.54%); Classification: neutrophilic granulocyte≤50%9 examples (40.90%),＞50%12 examples (54.54%), 1 example＞90%.Clinical diagnosis: upper respiratory tract infection 13 examples (59.09%), bronchitis 6 examples (27.28%), bronchopneumonia 2 examples (9.09%) (wherein 1 routine pneumonia rabat confirms), bronchiolitis 1 example (4.45%).
1.2 matched group 20 examples, male 9 examples, women 11 examples, 3.8 years old mean age (3.5～12 years old).8 examples of generating heat (40.00%), red swelling of the pharynx ++～+++15 examples (75.00%).10 examples are done blood examination on every side, leukocyte＞10 * 10
9/ L8 example, neutrophilic granulocyte classification＞50%8 examples.Clinical diagnosis: upper respiratory tract infection 18 examples (90.00%), bronchitis 2 examples (10.00%).
2, method
The treatment group adopts the cefadroxil chewable tablet of the embodiment of the invention 1, supplies pharmaceutical quantities 30mg/kg every day body weight, and 2 times on the one oral.Matched group adopts the cefadroxil chewable tablet [Zhongqi Pharmaceutical Technology's development, specification 125mg/ sheet, lot number 060302] of prior art, supplies pharmaceutical quantities 30mg/kg every day body weight, and 2 times on the one oral.Each group all adopts single antibacterials during the treatment, symptomatic drugs such as be aided with relieving cough and resolving phlegm, bring down a fever.
3, evaluation of clinical curative effect
Produce effects: 3～6 days endosome temperature drops of taking medicine are to normal, and red swelling of the pharynx disappears, and pulmonary does moist rale and disappears, and General Symptoms disappears or obviously improves.Effectively: 3～6 days endosome relaxing the bowels with purgatives of warm nature of taking medicine fall, and red swelling of the pharynx alleviates, and General Symptoms alleviates.Invalid: taking medicine, body temperature does not descend in 3～6 days, and red swelling of the pharynx does not disappear, and pulmonary rale does not disappear, and General Symptoms does not improve, or because of serious side reaction drug withdrawal.
4, statistical method
Two groups of data are used X 2 test.
5, result
Treatment group produce effects 18 examples, effective 3 examples, total effective 21 examples (95.45%), invalid 1 example (4.55%); Matched group produce effects 10 examples, effective 7 examples, total effective 17 examples (85.00%), invalid 3 examples (15.00%).Through statistical analysis, two groups of curative effect differences have significance.
6, discuss
This Test Example data shows, treatment group total effective rate 95.45% (wherein produce effects accounts for 81.82%, effectively accounts for 13.63%), and matched group total effective rate 85.00% (produce effects accounts for 50.00%, effectively accounts for 35.00%).Through statistical procedures, two groups of curative effect differences have significance.Show that the cefadroxil chewable tablet treatment infantile respiratory tract infection property disease of the embodiment of the invention 1 obviously is superior to the cefadroxil chewable tablet of prior art.
Cefadroxil chewable tablet to other embodiment of the present invention has also carried out identical test, and the result of its acquisition is similar.
Claims (10)
1. a cefadroxil chewable tablet is characterized in that, described chewable tablet comprises following raw material components:
2. cefadroxil chewable tablet according to claim 1 is characterized in that, described chewable tablet comprises following raw material components:
3. cefadroxil chewable tablet according to claim 1 is characterized in that, described chewable tablet comprises following raw material components:
4. cefadroxil chewable tablet according to claim 1 is characterized in that, described chewable tablet comprises following raw material components:
5. the method for preparing of any described cefadroxil chewable tablet of claim 1-4 is characterized in that, this method comprises the steps:
1) respectively with cefadroxil, mannitol, maltodextrin, sucrose, aspartame and Mentholum crushing screening;
2) will spray into water again and granulate through cefadroxil, mannitol, maltodextrin, sucrose, aspartame, Mentholum and the Fructus Citri sinensis powdered flavor mix homogeneously of crushing screening of last step, drying obtains dried particles;
3) add magnesium stearate in the dried particles that upwards step obtains, mix homogeneously, tabletting promptly gets.
6. the method for preparing of cefadroxil chewable tablet according to claim 5 is characterized in that, the cefadroxil described in the step 1) was 100 mesh sieves; Described mannitol, maltodextrin, sucrose, aspartame and Mentholum were 80 mesh sieves.
7. the method for preparing of cefadroxil chewable tablet according to claim 5 is characterized in that, described step 2) described in mixing be blended in the comminutor in a step, the mixing in the step 3) is blended in dry-mixed machine; Wherein, rotating speed 30～70r/min mixes 5～20min when in comminutor, mixing; Rotating speed is 5～50r/min when in dry-mixed machine, mixing, and mixes 20～30min.
8. the method for preparing of cefadroxil chewable tablet according to claim 7 is characterized in that, rotating speed 50～70r/min mixes 5～10min when in comminutor, mixing.
9. the method for preparing of cefadroxil chewable tablet according to claim 5 is characterized in that, said preparation process is under ambient temperature 18-26 ℃, the condition of envionmental humidity 45%-65%, to carry out.
10. the method for preparing of cefadroxil chewable tablet according to claim 5 is characterized in that, described drying is to be dried to moisture 3%-6%.
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| CN102579455B (en) * | 2012-03-19 | 2014-02-19 | 迪沙药业集团有限公司 | Stable cefaclor chewing composition |
| CN109512791A (en) * | 2019-01-09 | 2019-03-26 | 佛山市南海东方澳龙制药有限公司 | A kind of pet Cefadroxil chewable tablets and preparation method thereof |
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| CN101467972A (en) * | 2007-12-29 | 2009-07-01 | 北京琥珀光华医药科技开发有限公司 | Ceftibuten chewable tablet |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101467972A (en) * | 2007-12-29 | 2009-07-01 | 北京琥珀光华医药科技开发有限公司 | Ceftibuten chewable tablet |
Non-Patent Citations (1)
| Title |
|---|
| 邓鸣等.头孢羟氨苄咀嚼片的人体生物等效性.《中国医院药学杂志》.2007,第27卷(第4期),461-463. * |
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