CN101444513B - Cefaclor orally disintegrating tablet and preparation method thereof - Google Patents
Cefaclor orally disintegrating tablet and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a Cefaclor orally disintegrating tablet and a preparation method thereof. The tablet comprises Cefaclor with pharmaceutically effective dose, pharmaceutically acceptable coating material, diluent, disintegrant, glidant, flavouring and lubricant. Ingredients, such as the coating material, the diluent, the disintegrant and the like, and contents are screened, and the preparation technology is improved by numerous studies by the applicant of the invention, thereby obtaining a prepared product with faster effect and more sufficient absorption. The tablet can be disintegrated or dissolved in more than ten seconds in an oral cavity by swallowing without drinking water. The tablet is more suitable for the elderly and patients with solid-swallowing difficulty, and provides great convenience for patients which are busy in work or can not take water conveniently.
Description
Technical field
The present invention relates to a kind of cefaclor oral disintegration tablet and preparation method thereof, belong to medical technical field.
Background technology
Cefaclor (cefaclor, CCL, cefaclor, trade name: Cefaclor, Cefaclor, Xin Kenuo, Shi Dagong, Cefaclor, Da Fukang), molecular formula is C
15H
14ClN
3O
4SH
2O, structural formula is as follows:
，H
2O
Cefaclor belongs to the oral cephalosporins of the second filial generation.Obtained the FDA approval in 1979 by U.S.'s development in 1976, nineteen eighty-two goes on the market in the U.S., promptly substitutes cefalexin and becomes the first situation of selling well antibiotic in the world then in 1985.In February, 1994 is domestic pushes cefaclor to Chinese market with trade name " Cefaclor ".Because cefaclor has has a broad antifungal spectrum, efficiently, outstanding advantage such as oral absorption is good, tissue distribution is wide, untoward reaction is slight, become current more satisfactory, the more reliable line antibiotic medicines of infectious disease such as respiratory tract, urinary tract, skin and soft tissue for the treatment of clinically.
Cefaclor is a wide spectrum semi-synthetic cephalosporins antibiotic.Activity to product penicillinase staphylococcus aureus, A group Hemolytic streptococcus, Streptococcus viridans and staphylococcus epidermidis is identical with cefadroxil, and is strong 2～4 times than cefadroxil to not producing enzyme staphylococcus aureus and pneumococcal antibacterial action.Gram negative bacilli is comprised the activity of escherichia coli and Klebsiella Pneumoniae etc. strong than cefalexin, similar with cefadroxil, strong to the activity of proteus mirabilis, Salmonella and Shigella than cefadroxil.2.9 this product of～8mg/L can suppress all hemophilus influenzas, comprises the drug-fast bacterial strain in ampicillin.Moraxelle catarrhalis and Diplococcus gonorrhoeae are very sensitive to this product.The positive Bacillus proteus of indole, Serratia, acinetobacter and Pseudomonas aeruginosa are all to the cefaclor drug resistance.
The dosage form that cefaclor is commonly used clinically has at present: tablet, capsule etc.As application number is 200510112546.7 Chinese patent, and dosage form is a capsule, and application number is 200610152609 Chinese patent, and dosage form is capsule, tablet drop pill etc.The oral formulations of cefaclor needs water to swallow when taking, and this has brought many inconveniences to fetch water inconvenient patient or the inconvenient patient of function of deglutition etc., has reduced the compliance of patient treatment.
Therefore in order to adapt to various crowd demands, particularly some old peoples, child or swallow the patient that medicine has obstacle, the present patent application preparation is an oral cavity disintegration tablet, said preparation can disintegrate fast in the oral cavity under anhydrous condition, enters digestive tract with swallowing act.Be characterized in: do not need when A. takes water just can be in the oral cavity disintegrate rapidly, for old man, infant and be busy with one's work, patient anhydrous or water intaking inconvenience provides great convenience; B. compare with common oral preparation, extensively covered by the oral fast solubility preparation because of gastrointestinal tract mucous, can reach effective blood drug level sooner, onset is rapid; C. the suitable adjuvant that adds correctives or cover bad smell in prescription uses compliance thereby improve the patient.Development this product has great social significance and good market prospect.
Though cefaclor oral disintegration tablet has had correlational study at present, it as application number 200410062748 Chinese patent, application number is 200310106591.2 Chinese patent, but the present patent application people is by big quantity research, to coating material in the oral cavity disintegration tablet, disintegrating agent, components such as fluidizer and content screen, preparation technology is improved, make that the product onset of preparation is faster, absorb more abundant, gastrointestinal is still less residual, it only need get final product rapid disintegrate or dissolving in tens seconds in the oral cavity, need not drink water, can finish with swallowing act and to take medicine, especially be fit to the old people and the inconvenient patient of solid that swallows, simultaneously also for being busy with one's work or getting not that water patient just provides very big convenience.
Summary of the invention
The object of the present invention is to provide a kind of cefaclor oral disintegration tablet.
Another object of the present invention is to provide the preparation method of above-mentioned cefaclor oral disintegration tablet.
A kind of cefaclor oral disintegration tablet provided by the invention comprises the cefaclor of pharmacy effective dose, pharmaceutically acceptable coating material, diluent, disintegrating agent, fluidizer, correctives and lubricant, and per thousand each constituent contents are as follows:
Cefaclor ... 20-800g
Coating material ... 2.1-460g
Diluent ... 20-500g
Disintegrating agent ... 1-160g
Fluidizer ... 0.1-80g
Correctives ... 1-60g
Lubricant ... 0.1-50g.
Wherein said coating material is polyacrylic resin IV, Eudragit
NE30D and ethyl cellulose, described diluent is a mannitol, described disintegrating agent is crospolyvinylpyrrolidone and low-substituted hydroxypropyl cellulose, described fluidizer is micropowder silica gel, described correctives is an Aspartane, described lubricant is a magnesium stearate, and per thousand each constituent contents are as follows:
Cefaclor ... 20-800g
Polyacrylic resin IV ... 1-200g
Eudragit
NE30D…………………………………………0.1-60g
Ethyl cellulose ... 1-200g
Mannitol ... 20-500g
Crospolyvinylpyrrolidone ... 0.5-80g
Low-substituted hydroxypropyl cellulose ... 0.5-80g
Micropowder silica gel ... 0.1-80g
Aspartane ... 1-60g
Magnesium stearate ... 0.1-50g.
Most preferably per thousand each constituent contents are as follows:
Cefaclor ... 125-250g
Polyacrylic resin IV ... 5-30g
Eudragit
NE30D…………………………………………1-3g
Ethyl cellulose ... 5-30g
Mannitol ... 40-120g
Crospolyvinylpyrrolidone ... 5-20g
Low-substituted hydroxypropyl cellulose ... 2-10g
Micropowder silica gel ... 1-3g
Aspartane ... 2-10g
Magnesium stearate ... 2-5g
The present invention also provides the preparation method of above-mentioned cefaclor oral disintegration tablet, comprises
1.. coating material is dissolved in adequate amount of ethanol fully stirs and make dissolving, add an amount of fluidizer again and keep stirring and make the even suspendible of fluidizer, standby as the capsule material;
2.. residue fluidizer mix homogeneously in cefaclor and the recipe quantity, place fluid bed, adopt air suspension to prepare microcapsule, detect the content of microcapsule, standby;
3.. the cefaclor microcapsule for preparing is sieved, standby;
4.. get the recipe quantity diluent and make soft material with an amount of water, the oven dry of sieving, granulate is standby;
5.. in the prescription ratio get cefaclor microcapsule and diluent particle, disintegrating agent, correctives mixes, and adds lubricant behind the mix homogeneously;
6.. tabletting.
Wherein, described coating material is polyacrylic resin IV, Eudragit
NE30D and ethyl cellulose, described diluent is a mannitol, and described disintegrating agent is crospolyvinylpyrrolidone and low-substituted hydroxypropyl cellulose, and described fluidizer is micropowder silica gel, described correctives is an Aspartane, and described lubricant is a magnesium stearate.
Screen cloth is the 0.6mm screen cloth when described in the preparation process cefaclor microcapsule for preparing being sieved; Described diluent is made soft material with an amount of water, and sieve is 30 mesh sieves when sieving oven dry; Described tabletting diameter is 12mm.
It below promptly is content of the present invention.Those skilled in the art all know, the key of preparation oral cavity disintegration tablet is to seek proper supplementary material, and good fluidity, compressibility are strong when guaranteeing tabletting, and disintegrate is fast, requires prepared tablet good mouthfeel in addition.Innovation part of the present invention is component such as coating material, disintegrating agent, fluidizer in the oral cavity disintegration tablet and content are screened, and preparation technology is improved, and makes that the product onset of preparation is faster, it is more abundant to absorb, and concrete characteristics are as follows:
1, on the preparation technology, the present invention in addition principal agent cefaclor of fluidizer is prepared into micron-sized microcapsule with coating material earlier, simultaneously diluent is granulated separately, granulate, compared with conventional pressed disc method, be convenient to mixing like this, content is accurate, and produce sliver, sticking and piebaldism phenomenon tabletting can be avoided the time, and overcome the shortcoming of cefaclor bitter in the mouth, dissolubility little (1: 100), and improving its bioavailability and stability, concrete outcome can be referring to experimental example 2.
2, coating material is selected polyacrylic resin IV, Eudragit
NE30D and ethyl cellulose, polyacrylic resin IV are Dimethylaminoethyl Methacrylate and methyl acrylic ester copolymer; Eudragit
NE30D is ETHYL CYANOACRYLATE and methymethacrylate (2: 1) copolymer, and is water insoluble, medium permeability, and 30% aqueous dispersion is an emulsion polymeric product, and the plasticity of NE30D is better, and easily film forming need not to add plasticizer; Ethyl cellulose do not have smell, tasteless, can form tough clothing film.The inventor is through experimental results demonstrate, use these 3 kinds of materials as coating material, than other coating material commonly used, as gelatin etc., granule is more neat in pelletization, and the product dissolution that makes is better, and 3 mix use, effect is better than independent result of use, the visible experimental example 1 of concrete outcome.
3, disintegrating agent is selected the mixture of low-substituted hydroxypropyl cellulose and crospolyvinylpyrrolidone, and low-substituted hydroxypropylcellulopowder powder has very big specific surface area and porosity, thereby bigger rate of moisture absorption and water absorption are arranged, and has increased dilatancy; Crospolyvinylpyrrolidone has high molecular and cross-linked structure, water insoluble but chance water can be introduced water rapidly, impel its network structure to expand and produce disintegration,, thereby can increase stability of drug simultaneously because thereby the hydroxy that molecule has on amido link and the adsorbing polyphenols molecule forms hydrogen bond.
4, diluent is selected mannitol for use, make made tablet surface smooth and beautiful appearance, the good no sand type of distinguishing the flavor of, and because of when dissolving heat absorption, dissolve in the oral cavity and have refrigerant sense, mannitol also plays the effect of porogen simultaneously, when taking product of the present invention, mannitol is met body fluid and is produced many micropores, helps the stripping of cefaclor, increases its bioavailability.
Therefore the present patent application people is by big quantity research, components such as coating material, disintegrating agent, fluidizer in the oral cavity disintegration tablet and content are screened, preparation technology is improved, make that product onset of the present invention is faster, absorption is more abundant, gastrointestinal is still less residual, it only need get final product rapid disintegrate or dissolving in tens seconds in the oral cavity, need not drink water, can finish with swallowing act and to take medicine, especially be fit to the old people and the inconvenient patient of solid that swallows, simultaneously also for being busy with one's work or getting not that water patient just provides very big convenience.
The specific embodiment
Embodiment 1
Per thousand each constituent contents are as follows:
Cefaclor ... 250g
Polyacrylic resin IV ... 30g
Eudragit
NE30D…………………………………………?3g
Ethyl cellulose ... 30g
Mannitol ... 120g
Crospolyvinylpyrrolidone ... 20g
Low-substituted hydroxypropyl cellulose ... 10g
Micropowder silica gel ... 3g
Aspartane ... 10g
Magnesium stearate ... 5g
Preparation method:
1.. with polyacrylic resin IV, Eudragit
The adequate amount of ethanol that is dissolved in NE30D and ethyl cellulose fully stirs and makes dissolving, adds to keep after recipe quantity 20% micropowder silica gel stirring making the even suspendible of micropowder silica gel again, and is standby as the capsule material;
2.. cefaclor and recipe quantity 80% micropowder silica gel mix homogeneously, place fluid bed, adopt air suspension to prepare microcapsule, detect cefaclor content, standby;
3.. the cefaclor microcapsule for preparing is crossed the 0.60mm screen cloth sieve, standby;
4.. get recipe quantity mannitol and make soft material with an amount of water, dry 2h behind 30 mesh sieves excessively, granulate is standby;
5.. in the prescription ratio get cefaclor microcapsule and mannitol particles, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, aspartame mixes, and adds magnesium stearate behind the mix homogeneously;
6.. get the intermediate hopper of packing into, the 12mm stamping.
Embodiment 2
Per thousand each constituent contents are as follows:
Cefaclor ... 125g
Polyacrylic resin IV ... 5g
Eudragit
NE30D…………………………………………1g
Ethyl cellulose ... 5g
Mannitol ... 40g
Crospolyvinylpyrrolidone ... 5g
Low-substituted hydroxypropyl cellulose ... 2g
Micropowder silica gel ... 1g
Aspartane ... 2g
Magnesium stearate ... 2g
Preparation method:
1.. with polyacrylic resin IV, Eudragit
The adequate amount of ethanol that is dissolved in NE30D and ethyl cellulose fully stirs and makes dissolving, adds to keep after recipe quantity 20% micropowder silica gel stirring making the even suspendible of micropowder silica gel again, and is standby as the capsule material;
2.. cefaclor and recipe quantity 80% micropowder silica gel mix homogeneously, place fluid bed, adopt air suspension to prepare microcapsule, detect cefaclor content, standby;
3.. the cefaclor microcapsule for preparing is crossed the 0.60mm screen cloth sieve, standby;
4.. get recipe quantity mannitol and make soft material with an amount of water, dry 2h behind 30 mesh sieves excessively, granulate is standby;
5.. in the prescription ratio get cefaclor microcapsule and mannitol particles, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, aspartame mixes, and adds magnesium stearate behind the mix homogeneously.
6.. get the intermediate hopper of packing into, the 9mm stamping.
Embodiment 3
Per thousand each constituent contents are as follows:
Cefaclor ... 62.5g
Polyacrylic resin IV ... 5g
Eudragit
NE30D?…………………………………………0.5g
Ethyl cellulose ... 5g
Mannitol ... 25g
Crospolyvinylpyrrolidone ... 4g
Low-substituted hydroxypropyl cellulose ... 2g
Micropowder silica gel ... 0.6g
Aspartane ... 2g
Magnesium stearate ... 1g
Preparation method:
1.. with polyacrylic resin IV, Eudragit
The adequate amount of ethanol that is dissolved in NE30D and ethyl cellulose fully stirs and makes dissolving, adds to keep after recipe quantity 20% micropowder silica gel stirring making the even suspendible of micropowder silica gel again, and is standby as the capsule material;
2.. cefaclor and recipe quantity 80% micropowder silica gel mix homogeneously, place fluid bed, adopt air suspension to prepare microcapsule, detect cefaclor content, standby;
3.. the cefaclor microcapsule for preparing is crossed the 0.60mm screen cloth sieve, standby;
4.. get recipe quantity mannitol and make soft ability with an amount of water, dry 2h behind 30 mesh sieves excessively, granulate is standby;
5.. in the prescription ratio get cefaclor microcapsule and mannitol particles, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, aspartame mixes, and adds magnesium stearate behind the mix homogeneously.
6.. get the intermediate hopper of packing into, the 6mm stamping.
Embodiment 4
Per thousand each constituent contents are as follows:
Cefaclor ... 500g
Polyacrylic resin IV ... 130g
Eudragit
NE30D…………………………………………?40g
Ethyl cellulose ... 130g
Mannitol ... 400g
Crospolyvinylpyrrolidone ... 60g
Low-substituted hydroxypropyl cellulose ... 60g
Micropowder silica gel ... 50g
Aspartane ... 40g
Magnesium stearate ... 30g
Preparation method:
1.. with polyacrylic resin IV, Eudragit
The adequate amount of ethanol that is dissolved in NE30D and ethyl cellulose fully stirs and makes dissolving, adds to keep after recipe quantity 20% micropowder silica gel stirring making the even suspendible of micropowder silica gel again, and is standby as the capsule material;
2.. cefaclor and recipe quantity 80% micropowder silica gel mix homogeneously, place fluid bed, adopt air suspension to prepare microcapsule, detect cefaclor content, standby;
3.. the cefaclor microcapsule for preparing is crossed the 0.60mm screen cloth sieve, standby;
4.. get recipe quantity mannitol and make soft ability with an amount of water, dry 2h behind 30 mesh sieves excessively, granulate is standby;
5.. in the prescription ratio get cefaclor microcapsule and mannitol particles, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, aspartame mixes, and adds magnesium stearate behind the mix homogeneously.
6.. get the intermediate hopper of packing into, the 22mm stamping.
Embodiment 5
Per thousand each constituent contents are as follows:
Cefaclor ... 20g
Polyacrylic resin IV ... 1g
Eudragit
NE30D?…………………………………………0.1g
Ethyl cellulose ... 1g
Mannitol ... 20g
Crospolyvinylpyrrolidone ... 0.5g
Low-substituted hydroxypropyl cellulose ... 0.5g
Micropowder silica gel ... 0.1g
Aspartane ... 1g
Magnesium stearate ... 0.1g
Preparation method:
1.. with polyacrylic resin IV, Eudragit
The adequate amount of ethanol that is dissolved in NE30D and ethyl cellulose fully stirs and makes dissolving, adds to keep after recipe quantity 20% micropowder silica gel stirring making the even suspendible of micropowder silica gel again, and is standby as the capsule material;
2.. cefaclor and recipe quantity 80% micropowder silica gel mix homogeneously, place fluid bed, adopt air suspension to prepare microcapsule, detect cefaclor content, standby;
3.. the cefaclor microcapsule for preparing is crossed the 0.60mm screen cloth sieve, standby;
4.. get recipe quantity mannitol and make soft ability with an amount of water, dry 2h behind 30 mesh sieves excessively, granulate is standby;
5.. in the prescription ratio get cefaclor microcapsule and mannitol particles, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, aspartame mixes, and adds magnesium stearate behind the mix homogeneously.
6.. get the intermediate hopper of packing into, the 5.5mm stamping.
Embodiment 6
Per thousand each constituent contents are as follows:
Cefaclor ... 800g
Polyacrylic resin IV ... 200g
Eudragit
NE30D?…………………………………………60g
Ethyl cellulose ... 200g
Mannitol ... 500g
Crospolyvinylpyrrolidone ... 80g
Low-substituted hydroxypropyl cellulose ... 80g
Micropowder silica gel ... 80g
Aspartane ... 60g
Magnesium stearate ... 50g
Experimental example 1
This experimental example is the screening experiment of coating material of the present invention, other component is constant with reference to embodiment 1, the coating material of selecting has gelatin, Polyethylene Glycol, ethyl cellulose and three kinds of components of the present invention, and gelatin is also investigated with indexs such as particle appearance, flowability and dissolutions.
Whether investigate particle appearance and be the wet feed that will make and be put in the standard screen porpoising 3 times, observing granule has broken situation.
Mobile investigate with angle of repose α≤30 ° flowability for well, α＞35 °, mobile general, α 〉=40 °, mobile is poor.
Dissolution is weighed with quality standard according to clinical research, promptly 30 minutes sampling and measuring, dissolution 〉=80%.The selection result sees Table 1
The mg of table 1 unit
As seen from the above table, prescription 1 and 2 granules are more neat, and granule is neat in the prescription 3, but dissolution is all not as prescription 4.
The product of embodiment 2-5 is done same screening experiment, obtain identical result.
So coating material is mixed into good for three kinds with the present invention.
Experimental example 2
This experimental example is the stability of drug products contrast, not prepare microcapsule, (concrete grammar is seen " pharmaceutics " the 4th edition P326 and directly utilize conventional pressed disc method, the People's Health Publisher, the Bi Dianzhou chief editor) cefaclor oral disintegration tablet of preparation is a reference preparation, the improvement of preparation method of the present invention is described, each constituent content is all as embodiment 1 in two kinds of method medicines.
The oral cavity disintegration tablet sample of getting the oral cavity disintegration tablet of embodiment 1 preparation and the preparation of conventional pressed disc method is an amount of, is tiled in the plate, under 4500Lx illuminance light, placed 10 days, and in the 0th, 5,10 day sampling at interval, mensuration.The results are shown in Table 2 and table 3
Table 2 embodiment 1 preparing product high light experiment irradiation result of the present invention
| Standing time (my god) | Divide (falling) hydrolysis products (%) | Dissolution (%) (45min) | Content (being equivalent to labelled amount 100%) |
| 0 5 | 0.36 2.13 | 98.7 93.2 | 101.4 95.5 |
| 10 | 2.47 | 93.1 | 94.8 |
The conventional pressed disc method preparing product irradiation of table 3 result
| Standing time (my god) | Divide (falling) hydrolysis products (%) | Dissolution (%) (45min) | Content (being equivalent to labelled amount 100%) |
| 0 5 10 | 0.35 2.46 2.75 | 96.1 90.5 90.1 | 99.6 94.2 92.9 |
As seen, under equal illumination condition, preparation method of the present invention is more stable than the product of conventional pressed disc method method preparation.
Product to embodiment 2-5 carries out same processing, leads to the same conclusion.
Experimental example 3
This experimental example (is numbered B for embodiment 3 products and cefaclor oral disintegration tablet 1 (be numbered A, be that 200410062748.0 Chinese patent embodiment 3 prepare according to application number), cefaclor oral disintegration tablet 2, according to application number is 200310106591.2 Chinese patent embodiment, 1 preparation) dissolution experiment and comparison disintegration, the results are shown in Table 4 and table 5:
Table 4
| Dissolution | |||
| Sample time | Embodiment 1 | A | B |
| 5 10 20 30 | 20.3 42.5 77.2 98.7 | 20.1 40.0 75.7 96.6 | 19.9 43.6 76.3 97.4 |
Table 5
| Disintegration | |||
| Sequence number | Embodiment 1 | A | B |
| 123456 meansigma methodss | 20.1 19.4 19.8 20.2 19.9 19.6 19.8 | 28.1 29.0 28.7 29.6 29.3 28.5 28.9 | 29.9 30.6 31.3 30.4 30.8 31.5 30.8 |
As seen, the application's product has rapid-action, and disintegrate is fast, characteristics such as dissolution height, bioavailability height.
Product to embodiment 1,2,4 and 5 carries out same processing, leads to the same conclusion.
Experimental example 4
1. test objective
This test is intended to study the relative bioavailability of the cefaclor oral disintegration tablet of the present patent application, to determine whether the reference preparation gift identical with commercially available dosage comes Suzhou pharmaceutical Co. Ltd cefaclor dry suspension to have bioequivalence for it.
2. content of the test
2.1 object of study
The experimenter is the male, and the age is 22～27 years old, body weight 55～70kg, and height is 164～180cm, BMI is no tobacco and wine hobby in 19～25 scopes.No abnormal before the test through disease history inquire, physical examination and lab testing.Experimenter's medicine-less allergy history and drug dependence history, the medical history that is a cup too low and other chronic medical history.Do not obey any medicine in two weeks.Unified light diet during being tried.Test is the approval of refined three Medical Ethics committee of hospital through Central South University Hunan, and the experimenter all signs Informed Consent Form.
2.2 EXPERIMENTAL DESIGN
This research for open, at random, single center test of intersections, three cycles, oral administration, the cleaning phase of two phases between studying is 3 days.The experimenter is totally 18 people.The blood drug level of different time cefaclor after the administration of employing HPLC method mensuration.Utilize DAS Ver2.0 calculating pharmacokinetic parameters and carry out statistical analysis.Experimenter's random packet and take medicine.
2.3 medicine source and specification, lot number, usage and dosage
Reference preparation (R): gift comes the cefaclor dry suspension of Suzhou pharmaceutical Co. Ltd, specification: 0.125g; Lot number: 060306.Usage:, take after mixing it with water with 300mL warm water with 4 bags of cefaclor dry suspension.Consumption: 0.5g; Effect duration: in March, 2008; Storage: the hermetically drying place preserves.
Test preparation (A medicine): the cefaclor oral disintegration tablet of the embodiment of the invention 1, specification: 0.25g; Lot number: 060701.Usage: medicine is placed lingual surface, and water not need not to chew yet, and after the disintegrate, borrows swallowing act that medicine is swallowed rapidly.Consumption: 0.5g; Effect duration: in June, 2008; Storage: the hermetically drying place preserves.
Test preparation (B medicine): the development of Zhuhai Jin Hong pharmaceutcal corporation, Ltd, the cefaclor dry suspension of producing, specification: 0.125g; Lot number: 051101.Usage:, take after mixing it with water with 300mL warm water with 4 bags of cefaclor dry suspension.Consumption: 0.5g; Effect duration: in October, 2007; Storage: the hermetically drying place preserves.
3. process of the test
At one night of experimenter's fasting before the test, test was unified breakfast in the clinical observation chamber and take medicine morning on the same day.After taking medicine, the experimenter prohibits water, fasting 2 hours, and sampling is not left the clinical observation chamber before finishing.Duration of test is unified light diet.The first round tests after 5 hours and finishes.Write down accurate blood sampling time and adverse effect by research worker in the process of the test.Began after the elution time second to take turns test down through 3 days.Second takes turns after the off-test through beginning third round test after 3 days elution times
4. adverse events
The experimenter is observed by the clinician and the experienced nurse that participated in the GCP training in the process of the test, does not see that adverse events takes place.
5. biological specimen collection
Get 10min, 20min after blank blood sample (), the administration, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h hour before taking medicine at 0 o'clock from venous blood collection 5ml.Centrifugal immediately, blood plasma is in-20 ℃ of preservations.
6. the assay method of biological sample
Blood drug level adopts HPLC to measure.
7. result and discussion
Reference preparation cefaclor dry suspension (R) and be respectively by main pharmacokinetic parameter Cmax, Tmax, AUC0 → t and the AUC0 → ∞ (mean ± standard deviation) of test preparation cefaclor oral disintegration tablet (A), cefaclor dry suspension (B): 6.02 ± 2.17,5.01 ± 2.00 and 6.28 ± 2.66 μ g/ml; 0.66 ± 0.29,0.82 ± 0.34 and 0.66 ± 0.27h; 7.17 ± 2.19,7.05 ± 2.13 and 7.17 ± 2.14 μ gh/ml; 7.38 ± 2.25,7.25 ± 2.19 and 7.47 ± 2.23 μ gh/ml.Test preparation to the relative bioavailability F of reference preparation (with AUC0 → t as estimate according to) A/R is: 100.0% ± 21.3% (58.2%～132.2%), B/R is: 102.3% ± 23.4% (54.2%～143.9%).
Tmax tests through non-engaging in an inspection, different preparation differences there was no significant difference (A and R: U=0.290, p=0.772; B and R: U=0.703, p=0.482).AUC0 → t, AUC0 → ∞ and Cmax carry out variance analysis after to number conversion, and the result shows: both between different preparations and the different cycles differences do not have significance meaning (p＞0.05).Two one-side t-the assays of Cmax, AUC0 → t and AUC0 → ∞ show that thigh and tlow are all greater than one-side t 0.05.90% credibility interval of test preparation AUC0 → 48 and AUC0 → ∞ does not all exceed 80%～125% the scope of the corresponding AUC0 → t of reference preparation and AUC0 → ∞; 90% credibility interval of the Cmax of test preparation does not exceed 70%～143% the scope of reference preparation Cmax yet.
Above result shows, the reference preparation cefaclor dry suspension that the cefaclor oral disintegration tablet of the test preparation embodiment of the invention 1 is identical with dosage does not have the significance meaning in absorption by human body speed and absorbtivity difference, and two test preparations all have bioequivalence with reference preparation.
The oral cefaclor oral disintegration tablet of experimenter can be in the oral cavity disintegrate rapidly, no grittiness, good mouthfeel.
8. conclusion
The cefaclor oral disintegration tablet reference preparation cefaclor dry suspension identical with dosage according to the technical solution of the present invention preparation has bioequivalence.
Product to embodiment 2-5 carries out same processing, leads to the same conclusion.
In sum, the present patent application people is by big quantity research, components such as coating material, disintegrating agent, fluidizer in the oral cavity disintegration tablet and content are screened, preparation technology is improved, make that product onset according to the present invention is faster, it is more abundant to absorb, gastrointestinal is still less residual, it only need get final product rapid disintegrate or dissolving in tens seconds in the oral cavity, need not drink water, can finish with swallowing act and to take medicine, especially be fit to the old people and the inconvenient patient of solid that swallows, simultaneously also for being busy with one's work or getting not that water patient just provides very big convenience.
Claims (4)
1. a cefaclor oral disintegration tablet is characterized in that, comprises the cefaclor of pharmacy effective dose, pharmaceutically acceptable coating material, diluent, disintegrating agent, fluidizer, correctives and lubricant; Described coating material be polyacrylic resin IV,
NE30D and ethyl cellulose, described diluent is a mannitol, and described disintegrating agent is crospolyvinylpyrrolidone and low-substituted hydroxypropyl cellulose, and described fluidizer is micropowder silica gel, described correctives is an Aspartane, and described lubricant is a magnesium stearate; Per thousand each constituent contents are as follows in the described oral cavity disintegration tablet:
Cefaclor ... 125-250g
Polyacrylic resin IV ... 5-30g
Ethyl cellulose ... 5-30g
Mannitol ... 40-120g
Crospolyvinylpyrrolidone ... 5-20g
Low-substituted hydroxypropyl cellulose ... 2-10g
Micropowder silica gel ... 1-3g
Aspartane ... 2-10g
Magnesium stearate ... 2-5g;
The preparation method of described cefaclor oral disintegration tablet may further comprise the steps:
1.. coating material is dissolved in adequate amount of ethanol fully stirs and make dissolving, add an amount of fluidizer again and keep stirring and make the even suspendible of fluidizer, standby as the capsule material;
2.. residue fluidizer mix homogeneously in cefaclor and the recipe quantity, place fluid bed, adopt air suspension to prepare microcapsule, detect cefaclor content, standby;
3.. the cefaclor microcapsule for preparing is sieved, standby;
4.. get the recipe quantity diluent and make soft material with an amount of water, the oven dry of sieving, granulate is standby;
5.. in the prescription ratio get cefaclor microcapsule and diluent particle, disintegrating agent, correctives mixes, and adds lubricant behind the mix homogeneously;
6.. tabletting.
2. cefaclor oral disintegration tablet according to claim 1 is characterized in that, described when the cefaclor microcapsule for preparing is sieved screen cloth be the 0.6mm screen cloth; Described diluent is made soft material with an amount of water, and sieve is 30 mesh sieves when sieving oven dry; Described tabletting diameter is 12mm.
3. the preparation method of the described cefaclor oral disintegration tablet of claim 1 is characterized in that, may further comprise the steps:
1.. coating material is dissolved in adequate amount of ethanol fully stirs and make dissolving, add an amount of fluidizer again and keep stirring and make the even suspendible of fluidizer, standby as the capsule material;
2.. residue fluidizer mix homogeneously in cefaclor and the recipe quantity, place fluid bed, adopt air suspension to prepare microcapsule, detect cefaclor content, standby;
3.. the cefaclor microcapsule for preparing is sieved, standby;
4.. get the recipe quantity diluent and make soft material with an amount of water, the oven dry of sieving, granulate is standby;
5.. in the prescription ratio get cefaclor microcapsule and diluent particle, disintegrating agent, correctives mixes, and adds lubricant behind the mix homogeneously;
6.. tabletting.
4. the preparation method of cefaclor oral disintegration tablet according to claim 3 is characterized in that, described when the cefaclor microcapsule for preparing is sieved screen cloth be the 0.6mm screen cloth; Described diluent is made soft material with an amount of water, and sieve is 30 mesh sieves when sieving oven dry; Described tabletting diameter is 12mm.
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| CN2007101937952A CN101444513B (en) | 2007-11-27 | 2007-11-27 | Cefaclor orally disintegrating tablet and preparation method thereof |
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| CN2007101937952A CN101444513B (en) | 2007-11-27 | 2007-11-27 | Cefaclor orally disintegrating tablet and preparation method thereof |
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| CN101444513B true CN101444513B (en) | 2011-05-11 |
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| CN101791297B (en) * | 2010-02-10 | 2012-03-28 | 中国药科大学 | Atorvastatin calcium oral disintegrating tablet and preparation method thereof |
| CN101912373B (en) * | 2010-08-24 | 2012-01-04 | 北京京丰制药有限公司 | Stable cefeclor dispersible tablet and preparation method thereof |
| CN102357086A (en) * | 2011-11-01 | 2012-02-22 | 上海理工大学 | Cefprozil orally disintegrating tablets |
| CN116887866A (en) | 2020-12-03 | 2023-10-13 | 巴特尔纪念研究院 | Polymer nanoparticle and DNA nanostructure compositions and methods for non-viral delivery |
| WO2022216977A1 (en) | 2021-04-07 | 2022-10-13 | Batelle Memorial Institute | Rapid design, build, test, and learn technologies for identifying and using non-viral carriers |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1586485A (en) * | 2004-07-08 | 2005-03-02 | 北京阜康仁生物制药科技有限公司 | Cefaclor oral disintegration tablet |
| CN1923185A (en) * | 2006-10-16 | 2007-03-07 | 北京科信必成医药科技发展有限公司 | Gastrodine tablets disintegrating in oral cavity and process for producing same |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1586485A (en) * | 2004-07-08 | 2005-03-02 | 北京阜康仁生物制药科技有限公司 | Cefaclor oral disintegration tablet |
| CN1923185A (en) * | 2006-10-16 | 2007-03-07 | 北京科信必成医药科技发展有限公司 | Gastrodine tablets disintegrating in oral cavity and process for producing same |
Non-Patent Citations (1)
| Title |
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| 周建平.药剂学.药剂学.东南大学出版社,2007,(1),229-233. * |
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Assignee: Zhuhai Kinhoo Pharmaceutical Co.,Ltd. Assignor: Shang Guanqing Contract record no.: 2011440000276 Denomination of invention: Cefaclor orally disintegrating tablet and preparation method thereof License type: Exclusive License Open date: 20090603 Record date: 20110401 |
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