CN101077348A - Amoxicillin-clavulantes sustained release tablets - Google Patents
Amoxicillin-clavulantes sustained release tablets Download PDFInfo
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Abstract
The present invention discloses one kind of slow releasing amoxicillin/clavulanate tablet. The main medicine materials amoxicillin and clavulanate in certain ratio are added with slow releasing skeleton material to prepare solid dispersed preparation with slow release of the medicine components to maintain effective medicine concentration in blood and effect in long term. The medicine of the present invention has decreased taking time number, raised patient' s compliance, reduced blood medicine concentration peak-valley, raised safety, high bioavailability and other features.
Description
[technical field] the present invention relates to the slow releasing tablet of amoxicillin-clavulantes.
[background technology]
The research and development of slow releasing preparation, the history surplus in the of existing so far 40 year, it is in environment provided, non-lentamente on request perseverance is captured release, the preparation that medication every day number of times and corresponding ordinary preparation reduce once more at least or prolong to some extent blanking time of medication.This preparation can make human body keep this kind blood drug level to reach the long time, do not descend quickly the ordinary preparation and do not resemble, thereby " peak valley " phenomenon that can avoid the ordinary preparation frequent drug administration to be occurred, safety, effectiveness or the adaptability of medicine are increased, thereby reduced the medication number of times, greatly facilitate the patient, particularly the patient of long-term prescription.Peroral dosage form commonly used has matrix tablet, micropore bag pellicle controlled release tablet, laser osmotic pumps, composite particles chamber capsule, label chamber capsule, Entogastric lingering preparation, controlled release suspensoid, drop pill etc.; External preparation has eye therapy system, oral cavity sticking tablet, indoor knot medicine device, transdermal clam medicine system etc.; Injection has water suspendible chaste tree, newborn thorn, liposome, microsphere etc.Tablet is with its taking convenience, and preparation technology is simple relatively, and quality is easy to advantage such as control becomes most widely used, the most sophisticated dosage form of technology of slow releasing preparation research and development.Capsule is also with its taking convenience, and preparation technology is simple relatively, and quality such as is easy to control at advantage becomes a wider dosage form of slow releasing preparation research and development application prospect.Film coating sustained-release and controlled release preparation packs the suitable clothing layer of one deck on the surface of label and piller, it is dissolved under certain condition or be partly dissolved and discharge medicine, can reach the sustained-release and controlled release effect.Its principle belongs to diffusion and discharges, and the energy is based on the osmotic pressure of film intracavity, or the stripping dispersal behavior coated slow release controlled release preparation of drug molecule in polymer is one of type of extensive use in the oral sustained release controlled release preparation.
Slow releasing preparation belongs to third generation preparation in the development process of pharmaceutics.In recent years, the research and development development of slow releasing preparation rapidly, the slow releasing preparation that with the Western medicine is material medicine has carried out a large amount of research at pharmacokinetics design principle, adjuvant and moulding process, biopharmaceutics characteristic aspects such as (comprising medicine inside and outside release rule and influence thereof), and existing many sophisticated kinds such as aminophylline slow releasing tablet, cefaclor slow releasing tablet, cefalexin slow releasing capsule etc. are widely used in clinically.Chinese medicine is more complicated in this regard, the Chinese medicine compound preparation active component is often indeterminate, thereby cause in its dissolubility, partition coefficient, the stability in Digestive system and the body and the logical suitable property of the combination rate of blood plasma, medicine pK value and biomembrane between relation etc. indeterminate, thereby increased the difficulty of preparation, but it is clinical that more existing at present sophisticated kinds are used for, as ZHENGQINGFENGTONGNING slow releasing tablet, aescine gel sustained-release preparation etc.
According to its preparation technology's difference, slow releasing preparation can be divided into tablet, capsule, sustained-release dropping pill etc.Used substrate comprises hydrophilic gel sustained-release matrix material, as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer etc.; Erodible sustained-release matrix material is as stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc.; Water-insoluble sustained-release matrix material is as ethyl cellulose, zein etc.Along with being on the increase of substrate kind, preparation technology's is ripe day by day perfect, and slow releasing agent is extensive day by day in the application of Chinese-western medicine preparation, therefore existing medicine is carried out modified form, produce more medicament slow release dosage form, will greatly enrich drug market, improve quality of medical care.
The amoxicillin is the semi-synthetic penicillium sp rope of a kind of wide spectrum, the stronger bacteria cell wall ability that penetrates is arranged, by suppressing the glycosidase of antibacterial, make the bacteria cell wall biosynthesis block, formation spheroplast breaks and dissolves death rapidly, be the active drug that infects due to a kind of clinical practice wide range of therapeutic gram negative bacteria and the gram positive bacteria, but the independent use in amoxicillin mainly is applicable to the infection due to the sensitive organism that does not produce beta lactamase.Continually develop and be widely used in clinical along with antibiotic, caused drug-resistance of bacteria, antibacterial is day by day increased the drug resistance of common antibiotics.Antibacterial produces drug resistance through number of ways to antibiotic, wherein to produce beta lactamase.Use beta lactamase restrainer can improve the antibiotic antibacterial activity of some beta-lactam class greatly, and enlarge antimicrobial spectrum.The beta lactamase restrainer that is most widely used at present is a clavulanic acid.Clavulanic acid claims clavulanic acid again, is bacteriogenic natural lactamase restrainer, contains the beta-lactam ring in the structure, and antibacterial action is very weak, presses down the enzyme effect but have strong effect wide-spectrum.It with enzyme firm combining takes place makes enzyme deactivation, and the elimination with inhibitor does not bring back to life.The no clinical value of simple use, normal and other beta-lactam class antibiotic share, to strengthen antibacterial action.The beta lactamase that the beta lactamase that clavulanic acid produces staphylococcus aureus, gram negative bacilli produce has obvious inhibitory action.The amoxicillin is short medicine of a biological half-life, generally need the interval to give a medicine in about 6 hours, using to the patient makes troubles, simultaneously owing to influence the influence of factors such as dosing interval the length of one's sleep, affect the medicine steady plasma-drug concentration, thereby influence drug effect.The slow releasing tablet of the amoxicillin-clavulantes that the technology of the present invention is prepared can be administered once at interval in 12-24 hour, kept best steady plasma-drug concentration, improved drug effect, the convenient use.
[summary of the invention]
The technology of slow releasing tablet that the purpose of this invention is to provide the amoxicillin-clavulantes of preparation.
The present invention studies by experiment amoxicillin-clavulantes has been carried out modified form, changes slow releasing preparation into from existing tablet, capsule etc.Utilize medicament slow release framework material hydrophilic gel sustained-release matrix material, as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer etc.; Erodible sustained-release matrix material is as stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc.; Water-insoluble sustained-release matrix material, be aided with other common drug adjuvant as substrate such as ethyl cellulose, zein and selected medicine material and make solid preparation, make the non-lentamente as requested constant release of medicine, safety, effectiveness or the adaptability of medicine are increased, thereby reduced the medication number of times, greatly facilitate the patient, particularly the patient's of long-term prescription use.
Wherein, selected amoxicillin is chemical compound and its esters (as sodium salt, potassium salt, hydrochlorate, sulfate, hydrobromate, tartrate, the fumarate etc.) derivant with following feature: English Amoxicillin by name, molecular formula: C
16H
19N
3O
5S3H
2O, molecular weight: 419.46, chemical structural formula is:
Amoxicillin salt derivative commonly used is the amoxicillin sodium salt.
Wherein, selected clavulanic acid is chemical compound and its esters (as sodium salt, potassium salt, hydrochlorate, sulfate, hydrobromate, tartrate, the fumarate etc.) derivant with following feature: English Clavulanate by name, molecular formula: C
8H
8KNO
5, molecular weight: 237.25, chemical structural formula is:
Clavulanic acid salt derivative commonly used is a clavulanic acid potassium salt.
Wherein said slow releasing preparation is formed its Chinese medicine by amoxicillin and clavulanic acid and salt derivative thereof and substrate: sustained-release matrix material=1: 0.10-1: 5.0.Described substrate comprises the medicament slow release framework material: hydrophilic gel medicament slow release framework material, as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer etc.; Erodible medicament slow release framework material is as stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc.; Water-insoluble drug sustained-release matrix material comprises as ethyl cellulose, zein etc. and other additional materials:
1, diluent (filler): for example Icing Sugar, gelatin, glycerol, arabic gum, starch, dextrin, lactose, glucose, mannitol, calcium sulfate, calcium hydrogen phosphate, tricalcium phosphate, gelatinized corn starch, syrup, maltose, gelatine size, cellulose, Kaolin, sodium chloride, modified starch (Sta-RX1500), microcrystalline Cellulose etc., wherein Icing Sugar has sucrose, maltose, dextrinose, dextrinose oligosaccharide, panose, cottonseed sugar, stachyose, oligofructose, fructose, inulin, protein sugar, stevioside, xylitol, maltose alcohol, sorbitol;
2, binding agent: for example water, ethanol, starch, gelatin, sucrose, glucose, dextran, syrup, lactose, arabic gum, sodium alginate, gelatine size, polyvinylpyrrolidone, Polyethylene Glycol, methylcellulose, carboxymethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, maltose, sucrose dextrin copolymer;
3, disintegrating agent: for example starch (corn and potato starch), cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, pectin, carboxymethyl cellulose, microcrystalline Cellulose, tween 80, sodium laurylsulfate, stearyl alcohol sodium sulfonate, kaolin.
4, lubricant: for example stearic acid, calcium stearate, magnesium stearate, zinc stearate, hydrogenated vegetable oil, polyoxyethylene monostearate, light mineral oil, liquid paraffin, boric acid, sodium chloride, sodium benzoate, sodium acetate, enuatrol, sodium laurylsulfate (magnesium), single Laurel sucrose acid ester, adipic acid, fumaric acid, three triacetins, Polyethylene Glycol
1500～20000
5, fluidizer: for example starch, purified talc, micropowder silica gel, pyrolytic silicon dioxide, hydrated sodium aluminosilicate.
By the preparation method of following slow releasing preparation provided by the present invention, can further understand the present invention, but following description not a limitation of the invention:
With the medicine is primary raw material, according to certain ratio, adds medicament slow release framework material and additional materials as substrate, is prepared from through specific technology, apparatus processing again.Specific as follows:
(1) prescription: medicine+substrate;
Medicine: be foregoing medicine and its esters (as sodium salt, potassium salt, hydrochlorate, sulfate, hydrobromate, tartrate, fumarate etc.) derivant.
Substrate: include the medicament slow release framework material: hydrophilic gel medicament slow release framework material, as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer etc.; Erodible medicament slow release framework material is as stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc.; Water-insoluble drug sustained-release matrix material is as one or more composition and additional materials of ethyl cellulose, zein etc., its Chinese medicine: sustained-release matrix material=1: 0.10-1: 5.0.
(2) preparation technology: concrete implementation step is as follows:
Method one: according to certain ratio with medicine, erodible sustained-release matrix material, as stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc. and hydrophilic gel sustained-release matrix material, as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer etc. and the additives mix homogeneously of milling, direct compression or dry granulation behind the adding lubricant, tabletting or elder generation add typical binders granulation, drying behind the adding lubricant, add the lubricant tabletting again.
Method two: according to certain ratio with medicine, erodible sustained-release matrix material, as stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc. and additives mill jointly mix after, again with hydrophilic gel sustained-release matrix material, as mixing such as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomers, direct compression or dry granulation behind the adding lubricant, tabletting or elder generation add typical binders granulation, drying behind the adding lubricant, add the lubricant tabletting again.
Method three: according to certain ratio with medicine, additives and water-insoluble sustained-release matrix material, alcoholic solution mix homogeneously as ethyl cellulose, zein etc., add hydrophilic gel sustained-release matrix material, as mixing granulations such as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomers, dry, add lubricant, tabletting gets finished product.
Method four: according to certain ratio with water-soluble components in medicine, the described additives and water-insoluble sustained-release matrix material, alcoholic solution mix homogeneously or dissolving as ethyl cellulose, zein etc., vacuum drying, pulverize, add hydrophilic gel sustained-release matrix material, as mixing such as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomers, add the lubricant tabletting again behind adding lubricant direct compression or the dry granulation and get finished product.
Method five: with medicine, water-insoluble sustained-release matrix material, even with additives and mix lubricant as ethyl cellulose, zein etc., tabletting gets finished product according to certain ratio.
The amoxicillin slow release tablet that [beneficial effect] is involved in the present invention utilizes the sustained-release matrix material to comprise hydrophilic gel medicament slow release framework material, as hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer etc.; Erodible medicament slow release framework material is as stearic acid, hexadecanol, octadecanol, Polyethylene Glycol etc.; Water-insoluble drug sustained-release matrix material is made solid dispersion as ethyl cellulose, zein etc. for substrate and medicine material, makes medicine medicine after administration can be on request slowly continue to discharge keeping effective blood concentration, thereby reaches long-acting.
Compare with conventional formulation, medication preparation becomes to have its special advantages behind the slow releasing preparation: (1) reduces administration number of times, improves patient's compliance of taking medicine; (2) reduce the blood concentration peak valley phenomenon, improve drug effect and drug safety: (3) reduce the accumulated dose of medication, so that minimum dose reaches greatest treatment efficacy; (4) after medicine is made slowly released and controlled-drug delivery system with suitable carrier, the absorption of medicine and the main character decision that distributes by carrier, therefore select the appropriate carriers material according to clinical requirement, not only can conduct drugs to the particular target organ, can also improve the physicochemical property and the pharmacologically active of medicine to a certain extent, have broad clinical application prospect.
[specific implementation method]
By following concrete embodiment, can further understand the present invention, but following example not a limitation of the invention.
The preparation of embodiment 1-amoxicillin and clavulanate potassium slow releasing tablet (1)
Method: get amoxicillin and clavulanate potassium (2: 1) 375 grams, hydroxypropyl cellulose 20 grams, hypromellose 30 grams, lactose 10 grams, microcrystalline Cellulose 10 grams, carbomer 1 gram, Macrogol 4000 30 grams respectively, mix homogeneously, dry granulation, adding magnesium stearate mixes, tabletting gets finished product, and containing medication amount is the 375mg/ sheet.Measure the dissolution of amoxicillin and clavulanate potassium slow releasing tablet (1) in 37 ℃ of 900ml water then.The dissolution amoxicillin that the results are shown in Table 1,10 hour is 96%, and clavulanate potassium is 99%, meets per release request that was administered once in 12 hours.
The dissolution of table 1 amoxicillin and clavulanate potassium slow releasing tablet (1)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) amoxicillin and clavulanate potassium | 15.0 29.5 | 26.6 55.6 | 46.2 76.6 | 68.8 86.2 | 88.6 96.6 | 95.1 99.6 | 96.3 98.9 |
The preparation of embodiment 2-amoxicillin and clavulanate potassium slow releasing tablet (2)
Method: get amoxicillin and clavulanate potassium (2: 1) 187g, hypromellose 72g, microcrystalline Cellulose 23g, hyprolose 30g, stearic acid 30g, lactose 11g respectively, cross 80 mesh sieves respectively, mixing, 95% alcoholic solution that adds concentration and be 10% polyvinylpyrrolidone is as binding agent and stir and make soft material, crosses 16 mesh sieves and granulates, granule room temperature ℃ drying 2 hours, 16 mesh sieve granulate add magnesium stearate 4.5 grams, mixing again, tabletting gets finished product, and containing medication amount is the 187mg/ sheet.Measure the dissolution of amoxicillin and clavulanate potassium slow releasing tablet (1) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 2,10 hours is that the amoxicillin is 92%, and clavulanate potassium is 98%, meets per release request that was administered once in 12 hours.
The dissolution of table 2 amoxicillin and clavulanate potassium slow releasing tablet (2)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) amoxicillin and clavulanate potassium | 21.0 39.5 | 29.6 55.6 | 39.2 76.6 | 62.8 89.2 | 75.6 95.6 | 85.1 98.6 | 92.3 98.2 |
The preparation of embodiment 3-amoxicillin and clavulanate potassium slow releasing tablet (3)
Method: get amoxicillin and clavulanate potassium (4: 1) 250 gram, hydroxypropyl cellulose 20 grams, octadecanol 40 grams, hypromellose 10 grams, stearic acid 10 grams, lactose 10 grams respectively, cross 80 mesh sieves respectively, grind mixing, 95% alcoholic solution that adds concentration and be 10% polyvinylpyrrolidone is as binding agent and stir and make soft material, crossing 16 mesh sieves granulates, granule drying at room temperature 2 hours, 16 mesh sieve granulate, add magnesium stearate 4.5 grams, micropowder silica gel 2 grams again, mixing, tabletting gets finished product, and containing medication amount is the 250mg/ sheet.Measure the dissolution of amoxicillin and clavulanate potassium slow releasing tablet (3) in 37 ℃ of 900ml water then.The dissolution amoxicillin that the results are shown in Table 1,10 hour is 99%, and clavulanate potassium is 97%, meets per release request that was administered once in 12 hours.
The dissolution of table 3 amoxicillin and clavulanate potassium slow releasing tablet (3)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) amoxicillin and clavulanate potassium | 31.0 39.5 | 46.4 55.3 | 56.2 76.6 | 68.9 86.5 | 82.6 92.6 | 91.1 94.1 | 99.1 97.3 |
The preparation of embodiment 4-amoxicillin and clavulanate potassium slow releasing tablet (4)
Method: get amoxicillin and clavulanate potassium (4: 1) 250 grams, octadecanol 40 grams respectively, lactose 10 restrains, crosses respectively 80 mesh sieves, grind mixing, add hydroxypropyl cellulose 20 grams, hypromellose 20 grams, grind mixing, 95% alcoholic solution that adds concentration and be 10% polyvinylpyrrolidone is as binding agent and stir and make soft material, crossing 16 mesh sieves granulates, granule room temperature ℃ drying 2 hours, 16 mesh sieve granulate add magnesium stearate 4.5 grams, micropowder silica gel 2 grams, mixing again, tabletting gets finished product, and containing medication amount is the 250mg/ sheet.Measure the dissolution of amoxicillin and clavulanate potassium slow releasing tablet (4) in 37 ℃ of 900ml water then.The dissolution amoxicillin that the results are shown in Table 4,10 hours is 98%, and clavulanate potassium is 98%, meets per release request that was administered once in 12 hours.
The dissolution of table 4 amoxicillin and clavulanate potassium slow releasing tablet (4)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) amoxicillin and clavulanate potassium | 13.0 39.5 | 22.6 56.6 | 45.2 72.6 | 68.3 83.2 | 82.6 91.6 | 95.1 97.6 | 98.3 98.2 |
The preparation of embodiment 5-amoxicillin and clavulanate potassium slow releasing tablet (5)
Method: get amoxicillin and clavulanate potassium (6: 1) 250 grams, lactose 10 grams, ethyl cellulose 35 grams (alcoholic solution) respectively, mix homogeneously, add hydroxypropyl cellulose 10 grams, stearic acid 10 grams, mix homogeneously, 95% alcoholic solution that adds concentration and be 10% polyvinylpyrrolidone is as binding agent and stir and make soft material, crossing 16 mesh sieves granulates, granule drying at room temperature 2 hours, 16 mesh sieve granulate, add magnesium stearate 4.5 grams, micropowder silica gel 2 grams again, mixing, tabletting gets finished product, and containing medication amount is the 250mg/ sheet.Measure the dissolution of amoxicillin and clavulanate potassium slow releasing tablet (5) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 5,19 hours is that the amoxicillin is 99%, and clavulanate potassium is 98%, meets per release request that was administered once in 24 hours.
The dissolution of table 5 amoxicillin and clavulanate potassium slow releasing tablet (5)
| Sample time (hour) | 1 | 4 | 7 | 10 | 13 | 16 | 19 |
| Dissolution (%) amoxicillin and clavulanate potassium | 11.0 35.5 | 38.8 66.6 | 61.1 86.6 | 76.3 95.9 | 88.7 97.2 | 91.2 98.5 | 99.5 98.2 |
The preparation of embodiment 6-amoxicillin and clavulanate potassium slow releasing tablet (6)
Method: get amoxicillin and clavulanate potassium (6: 1) 250 grams, lactose 10 grams, ethyl cellulose 35 grams (alcoholic solution) respectively, mix homogeneously, dry, pulverize, add hydroxypropyl cellulose 10 grams, hypromellose 30 grams, mix homogeneously, 95% alcoholic solution that adds concentration and be 10% polyvinylpyrrolidone is as binding agent and stir and make soft material, cross 16 mesh sieves and granulate granule room temperature ℃ drying 2 hours, 16 mesh sieve granulate, add magnesium stearate 4.5 grams, micropowder silica gel 2 grams again, mixing, tabletting gets finished product, and containing medication amount is the 250mg/ sheet.Measure the dissolution of amoxicillin and clavulanate potassium slow releasing tablet (6) in 37 ℃ of 900ml water then.The dissolution amoxicillin that the results are shown in Table 6,19 hours is 96%, and clavulanate potassium is 98%, meets per release request that was administered once in 24 hours.
The dissolution of table 6 amoxicillin and clavulanate potassium slow releasing tablet (6)
| Sample time (hour) | 1 | 4 | 7 | 10 | 13 | 16 | 19 |
| Dissolution (%) amoxicillin and clavulanate potassium | 11.0 29.1 | 25.4 45.6 | 46.2 66.3 | 67.2 89.2 | 82.6 93.1 | 95.1 96.0 | 96.3 98.9 |
The preparation of embodiment 7-amoxicillin and clavulanate potassium slow releasing tablet (7)
Method: get amoxicillin and clavulanate potassium (8: 1) 250 grams, lactose 10 grams, ethyl cellulose 30 grams (alcoholic solution) respectively, mix homogeneously, drying is pulverized, 95% alcoholic solution that adds concentration and be 10% polyvinylpyrrolidone is as binding agent and stir and make soft material, cross 16 mesh sieves and granulate granule drying at room temperature 2 hours, 16 mesh sieve granulate, add magnesium stearate 4.5 grams, micropowder silica gel 2 grams again, mixing, tabletting gets finished product, and containing medication amount is the 250mg/ sheet.Measure the dissolution of amoxicillin and clavulanate potassium slow releasing tablet (7) in 37 ℃ of 900ml water then.The dissolution amoxicillin that the results are shown in Table 7,19 hours is 98%, and clavulanate potassium is 96%, meets per release request that was administered once in 24 hours.
The dissolution of table 7 amoxicillin and clavulanate potassium slow releasing tablet (7)
| Sample time (hour) | 1 | 4 | 7 | 10 | 13 | 16 | 19 |
| Dissolution (%) amoxicillin and clavulanate potassium | 15.0 39.5 | 46.2 66.6 | 88.6 82.6 | 70.3 95.9 | 82.4 96.1 | 91.3 97.3 | 97.8 96.0 |
The preparation of embodiment 8-amoxicillin sodium and clavulanate potassium slow releasing tablet
Method: get amoxicillin sodium and clavulanate potassium (4: 1) 250 gram, hydroxypropyl cellulose 20 grams, octadecanol 40 grams, hypromellose 10 grams, stearic acid 10 grams, lactose 10 grams respectively, cross 80 mesh sieves respectively, grind mixing, 95% alcoholic solution that adds concentration and be 10% polyvinylpyrrolidone is as binding agent and stir and make soft material, crossing 16 mesh sieves granulates, granule drying at room temperature 2 hours, 16 mesh sieve granulate, add magnesium stearate 4.5 grams, micropowder silica gel 2 grams again, mixing, tabletting gets finished product, and containing medication amount is the 250mg/ sheet.Measure the dissolution of amoxicillin sodium and clavulanate potassium slow releasing tablet in 37 ℃ of 900ml water then.The dissolution amoxicillin that the results are shown in Table 8,10 hours is 96%, and clavulanate potassium is 97%, meets per release request that was administered once in 12 hours.
The dissolution of table 8 amoxicillin sodium and clavulanate potassium slow releasing tablet
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) amoxicillin sodium and clavulanate potassium | 26.7 41.5 | 39.2 50.0 | 51.1 66.4 | 63.9 75.2 | 80.6 89.6 | 93.0 97.9 | 96.1 97.1 |
Claims (6)
1. slow releasing tablet, it contains sustained-release matrix material and additives in amoxicillin, Clavulanate and the tablet, wherein the weight ratio of amoxicillin and Clavulanate is n: 1, and n is the number of 2-8, the medicine in the tablet: sustained-release matrix material=1: 0.1-1: 5.0.
2. slow releasing tablet as claimed in claim 1, Clavulanate wherein is a clavulanate potassium, the amoxicillin is Utimox and salt derivative thereof.
3. slow releasing tablet as claimed in claim 1, wherein the toatl proportion between amoxicillin and the Clavulanate is preferred 2: 1,4: 1,6: 1,7: 1 or 8: 1.
4, slow releasing tablet according to claim 1 is characterized in that: described sustained-release matrix material is one or more a combination in any of hydrophilic gel sustained-release matrix material, erodible sustained-release matrix material, water-insoluble sustained-release matrix material.
5, sustained-release matrix material according to claim 2 is characterized in that: described hydrophilic gel sustained-release matrix material is one or more a combination in any of hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer; Described erodible sustained-release matrix material is one or more the combination in any in stearic acid, hexadecanol, octadecanol, the Polyethylene Glycol; Described water-insoluble sustained-release matrix material is that ethyl cellulose is or/and zein.
6, slow releasing tablet according to claim 1 is characterized in that: additives include lubricant and filler, binding agent, disintegrating agent, lubricant, fluidizer in the described slow releasing tablet.
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|---|---|---|---|
| CN 200610081120 CN101077348A (en) | 2006-05-22 | 2006-05-22 | Amoxicillin-clavulantes sustained release tablets |
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|---|---|---|---|
| CN 200610081120 CN101077348A (en) | 2006-05-22 | 2006-05-22 | Amoxicillin-clavulantes sustained release tablets |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103059045A (en) * | 2013-01-29 | 2013-04-24 | 黄明芳 | Novel amoxicillin sodium and clavulanate potassium compound and pharmaceutical composition thereof |
| CN103961350A (en) * | 2013-02-05 | 2014-08-06 | 西藏易明西雅生物医药科技有限公司 | Medicinal composition containing amoxicillin and potassium clavulanate |
-
2006
- 2006-05-22 CN CN 200610081120 patent/CN101077348A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103059045A (en) * | 2013-01-29 | 2013-04-24 | 黄明芳 | Novel amoxicillin sodium and clavulanate potassium compound and pharmaceutical composition thereof |
| CN103059045B (en) * | 2013-01-29 | 2014-08-20 | 黄明芳 | Novel amoxicillin sodium and clavulanate potassium compound and pharmaceutical composition thereof |
| CN103961350A (en) * | 2013-02-05 | 2014-08-06 | 西藏易明西雅生物医药科技有限公司 | Medicinal composition containing amoxicillin and potassium clavulanate |
| CN103961350B (en) * | 2013-02-05 | 2016-06-15 | 西藏易明西雅医药科技股份有限公司 | A kind of pharmaceutical composition containing amoxicillin and clavulanate potassium |
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