CN101011363A - Slow release tablet of amoxicillin - Google Patents
Slow release tablet of amoxicillin Download PDFInfo
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- CN101011363A CN101011363A CNA2006100986302A CN200610098630A CN101011363A CN 101011363 A CN101011363 A CN 101011363A CN A2006100986302 A CNA2006100986302 A CN A2006100986302A CN 200610098630 A CN200610098630 A CN 200610098630A CN 101011363 A CN101011363 A CN 101011363A
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Abstract
The invention discloses slow release tablets of Amoxicillin and process for preparation, wherein the raw materials of the preparation include Amoxicillin of a predetermined proportion, slow release matrix material and medicinal material, the preparation can be prepared into solid dispersing agent, wherein the medicament can be released slowly and continuously after being administrated, the effective concentration in blood can be maintained, and long action can be achieved. The advantages of the invention include decreased frequency of medicinal administration, improved patient's adaptability, lowered blood concentration peak-valley, increased medicinal effect and safety, and reduced total medicinal dose, thereby optimum curative effect can be achieved through minimum dose, thus the preparation is more suitable for patients.
Description
[technical field] the present invention relates to slow releasing tablet of amoxicillin and preparation method thereof.
[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 present clinical widely used oral antibiotic, is semi-synthetic penbritin class medicine.The amoxicillin can make bacterial cell become spheroplast and the dissolving of breaking rapidly by suppressing the biosynthesis of bacteria cell wall, thus the performance antimicrobial effect.To the significant curative effect that has that infects due to multiple gram negative bacteria and the gram positive bacteria, the clinical upper respiratory tract infection such as otitis media due to Streptococcus hemolyticus, streptococcus pneumoniae, staphylococcus or the hemophilus influenza, sinusitis, pharyngitis, tonsillitis that are used for; Urogenital infections due to escherichia coli, proteus mirabilis or the enterococcus faecalis; Skin soft-tissue infection due to Streptococcus hemolyticus, staphylococcus or the escherichia coli; Lower respiratory infections such as acute bronchitis, pneumonia due to Streptococcus hemolyticus, streptococcus pneumoniae, staphylococcus or the hemophilus influenza; Acute simple gonorrhea and typhoid fever, typhoid carrier and leptospirosis, the gastric and duodenal ulcers relevant with helicobacter pylori infections.The preparation of having succeeded in developing of this medicine has tablet, capsule, injection, chewable tablet etc.The amoxicillin is short medicine of a biology half-life, generally need give a medicine in about 6 hours in the interval, and using to the patient makes troubles, and owing to the influence of factors such as the length of one's sleep, affects the medicine steady plasma-drug concentration, thereby influences drug effect simultaneously.The technology of the present invention is the amoxicillin slow release sheet, can be administered once in 12-24 hour at interval, keeps best steady plasma-drug concentration, improves drug effect, the convenient use.
[summary of the invention]
The purpose of this invention is to provide slow releasing tablet of amoxicillin and preparation method thereof.
The present invention studies by experiment modified form has been carried out in the amoxicillin, changes slow releasing tablet 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 said slow releasing tablet is formed its Chinese medicine by amoxicillin and salt derivative thereof and substrate: sustained-release matrix material=1: 0.20-1: 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 tablet 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: 50.0.
(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 main absorption site of considering the amoxicillin is duodenum and jejunum, does not absorb substantially in colon.The absorption of medicine per os is about 4-6 hour to the time of leaving jejunum, and the complete drug release time of this preparation amoxicillin slow release sheet in digestive tract was greater than 8 hours.Discharge fully before jejunum is left in transhipment in order to ensure medicine, gastric retention type slow releasing tablet can further be made in the amoxicillin, prolong drug time of staying under one's belt whereby, medicine is discharged before leaving jejunum fully, transport gradually by duodenum and jejunum, reach the purpose that abundant absorption improves bioavailability.
But gastric retention system is the drug-supplying system of a kind of prolong drug at gastric transit time, comprises stomach floating system, gastric expansion system, bioadhesion system etc., and the most commonly used with the floating in stomach preparation.The floating in stomach drug-supplying system is meant can keep autologous density less than gastric content density after oral, is the preparation of floating state in gastric juice.It is to adopt that the present invention is designed to amoxicillin gastric floating preparation: (1) adds suitable floating material, as hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, take off ethylene chitin, polyvinyl alcohol, octadecanol, hexadecanol, glycerol monostearate cheese, spermol, stearyl alcohol, stearic acid, Cera Flava etc.; (2) add foaming agent, unite use as carbonate, bicarbonate or citric acid, tartaric acid, meet gastric acid and produce CO2 gas, bag quilt and surface gel layer are to reach the effect that reduces preparation density.
The present invention adds hydrophilic gelatin polymer, as hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, take off the ethylene chitin, the lipid that polyvinyl alcohol and density are little, aliphatic alcohols, fatty acid or wax class, as octadecanol, hexadecanol, glyceryl monostearate, spermol, stearyl alcohol, stearic acid, Cera Flavas etc. are as floating material, add foaming agent, as carbonate, bicarbonate or citric acid, tartaric acid is united use, make preparation in gastric juice, meet the carbon dioxide that acid produces trace, all the time under one's belt floating, the intragastric floating sustained-release tablet agent is made in the amoxicillin, thereby avoid medicine to enter the small intestinal section, thereby improved the curative effect of medicine by metabolism.In order to make preparation more effective, the medicine in the intragastric floating sustained-release tablet agent of described amoxicillin: floating and ratios other auxiliary material are 1: 0.1-1: 5.
The amoxicillin slow release sheet 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, as ethyl cellulose, zein etc. and floating and expanded material, as hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, take off the ethylene chitin, the lipid that polyvinyl alcohol and density are little, aliphatic alcohols, fatty acid or wax class, as octadecanol, hexadecanol, glyceryl monostearate, spermol, stearyl alcohol, stearic acid, Cera Flavas etc. are as floating material, add foaming agent, as carbonate, bicarbonate or citric acid, tartaric acid is united to use to wait and is made solid preparation as substrate and medicine material, make medicine medicine after administration can be on request slowly continue to discharge keeping effective blood concentration, thereby reach long-acting.
Compare with conventional formulation, medication preparation becomes to have its special advantages after the slow releasing tablet: (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 slow release sheet (1)
Method: get amoxicillin 375 grams, hydroxypropyl cellulose 50 grams, hypromellose 15 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 slow release sheet (1) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 1,10 hour is 92%, meets per release request that was administered once in 12 hours.
The dissolution of table 1 amoxicillin slow release sheet (1)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) | 10.2 | 19.3 | 27.0 | 43.4 | 63.0 | 87.1 | 92.3 |
The preparation of embodiment 2-amoxicillin slow release sheet (2)
Method: get amoxicillin 250 gram, hydroxypropyl cellulose 10 grams, octadecanol 20 grams, hypromellose 15 grams, carbomer 1 gram, 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, 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 slow release sheet (2) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 2,10 hours is 96%, meets per release request that was administered once in 12 hours.
The dissolution of table 2 amoxicillin slow release sheet (2)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) | 16.2 | 21.0 | 31.3 | 44.5 | 74.0 | 84.2 | 96.3 |
The preparation of embodiment 3-amoxicillin slow release sheet (3)
Method: get amoxicillin 250g, hypromellose 35g, microcrystalline Cellulose 5g, carbomer 1g 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, 60 ℃ of dryings of granule 1 hour, 16 mesh sieve granulate add magnesium stearate 2.5 grams, mixing again, tabletting gets finished product, and containing medication amount is the 250mg/ sheet.Measure the dissolution of amoxicillin slow release sheet (3) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 3,10 hours is 95%, meets per release request that was administered once in 12 hours.
The dissolution of table 3 amoxicillin slow release sheet (2)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 | 12 |
| Dissolution (%) | 6.3 | 16.2 | 22.2 | 53.3 | 79.6 | 85.0 | 95.2 | 101.3 |
The preparation of embodiment 4-amoxicillin slow release sheet (4)
Method: get amoxicillin 250 grams, octadecanol 20 grams respectively, lactose 10 restrains, crosses respectively 80 mesh sieves, grind mixing, add hydroxypropyl cellulose 10 grams, hypromellose 15 grams, carbomer 1 gram, 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, 60 ℃ of dryings of granule 1 hour, 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 slow release sheet (4) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 4,10 hours is 95%, meets per release request that was administered once in 12 hours.
The dissolution of table 4 amoxicillin slow release sheet (4)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) | 15.5 | 23.0 | 33.3 | 45.6 | 78.0 | 86.2 | 95.4 |
The preparation of embodiment 5-amoxicillin slow release sheet (5)
Method: get amoxicillin 250 grams, lactose 10 grams, ethyl cellulose 30 grams (alcoholic solution) respectively, mix homogeneously adds hydroxypropyl cellulose 10 grams, carbomer 1 gram, 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 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 slow release sheet (5) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 5,10 hours is 97%, meets per release request that was administered once in 12 hours.
The dissolution of table 5 amoxicillin slow release sheet (5)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) | 9.7 | 12.6 | 14.9 | 34.7 | 81.0 | 93.7 | 96.9 |
The preparation of embodiment 6-amoxicillin slow release sheet (6)
Method: get amoxicillin 250 grams, lactose 10 grams, ethyl cellulose 30 grams (alcoholic solution) respectively, mix homogeneously, dry, pulverize, add hydroxypropyl cellulose 10 grams, carbomer 1 gram, 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 slow release sheet (6) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 6,10 hours is 98%, meets per release request that was administered once in 12 hours.
The dissolution of table 6 amoxicillin slow release sheet (5)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) | 12.2 | 16.6 | 29.9 | 48.5 | 78.0 | 89.3 | 97.9 |
The preparation of embodiment 7-amoxicillin slow release sheet (7)
Method: get amoxicillin 250 grams, lactose 10 grams, ethyl cellulose 10 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 slow release sheet (7) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 7,10 hours is 95%, meets per release request that was administered once in 12 hours.
The dissolution of table 7 amoxicillin slow release sheet (7)
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) | 14.6 | 24.3 | 36.4 | 55.5 | 68.0 | 78.6 | 94.9 |
The preparation of embodiment 8-Amoxicillin Sodium slow releasing tablet
Method: get Amoxicillin Sodium 250 gram, hydroxypropyl cellulose 10 grams, octadecanol 20 grams, hypromellose 15 grams, carbomer 1 gram, 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 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 Sodium slow releasing tablet in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 8,10 hours is 97%, meets per release request that was administered once in 12 hours.
The dissolution of table 8 Amoxicillin Sodium slow releasing tablet
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 |
| Dissolution (%) | 17.2 | 26.0 | 39.2 | 54.5 | 76.5 | 91.2 | 97.3 |
The preparation of embodiment 9-amoxicillin slow release sheet (8)
Method: get amoxicillin 250 gram, hydroxypropyl cellulose 10 grams, octadecanol 50 grams, hypromellose 25 grams, carbomer 1 gram, 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 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 slow release sheet (8) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 9,19 hours is 97%, meets per release request that was administered once in 24 hours.
The dissolution of table 9 amoxicillin slow release sheet
| Sample time (hour) | 1 | 4 | 7 | 10 | 13 | 16 | 19 |
| Dissolution (%) | 7.2 | 16.0 | 29.2 | 38.5 | 56.5 | 71.2 | 92.3 |
The preparation of embodiment 10-amoxicillin slow release sheet (8)
Method: get amoxicillin 250 gram, hydroxypropyl cellulose 10 grams, octadecanol 50 grams, hypromellose 25 grams, carbomer 1 gram, 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, grain 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 slow release sheet (8) in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 10,19 hours is 97%, meets per release request that was administered once in 24 hours.
The dissolution of table 10 amoxicillin slow release sheet
| Sample time (hour) | 1 | 4 | 7 | 10 | 13 | 16 | 19 |
| Dissolution (%) | 7.2 | 16.0 | 29.2 | 38.5 | 56.5 | 71.2 | 92.3 |
The preparation of embodiment 11-amoxicillin floating slow releasing tablet
Method: get amoxicillin 250 grams, hypromellose 40 grams, sodium carboxymethyl cellulose 5g, carbomer 15 grams, octadecanol 10 grams, sodium bicarbonate 10g 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, crosses 16 mesh sieves and granulates, granule room temperature ℃ drying 2 hours, 16 mesh sieve granulate add magnesium stearate 3 grams, mixing again, tabletting gets finished product, and containing medication amount is the 250mg/ sheet.Measure dissolution and the flotation time in 37 ℃ 250ml simulated gastric fluids of amoxicillin floating slow releasing tablet in 37 ℃ of 900ml water then.The dissolution that the results are shown in Table 11,12 hours is 100%, meets per release request that was administered once in 12 hours, the flotation time of table 12 in 37 ℃ of simulated gastric fluids greater than 12 hours, meets the floating requirement that was administered once in per 12 hours.
The dissolution of table 11 amoxicillin floating slow releasing tablet
| Sample time (hour) | 0.5 | 1 | 2 | 4 | 6 | 8 | 10 | 12 |
| Dissolution (%) | 19.2 | 29.9 | 40.9 | 54.2 | 67.0 | 78.3 | 86.3 | 100.3 |
The floating experimental result of table 12 amoxicillin floating slow releasing tablet
| The test batch | 1 | 2 | 3 |
| Flotation time (hour) | More than 12 | More than 12 | More than 12 |
Claims (8)
1, the slow releasing tablet of amoxicillin is characterized in that: it contains amoxicillin and slow release framework material and additives substantially, its Chinese medicine: sustained-release matrix material=1: 0.20-1: 5.0.
2, 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.
3. slow releasing tablet according to claim 1 is characterized in that: described amoxicillin is Utimox and salt derivative thereof, and wherein the per unit preparation contains amoxicillin 50mg-500mg.
4, 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.
5, slow releasing tablet according to claim 1 is characterized in that: described slow releasing tablet also comprises the intragastric floating sustained-release tablet agent of amoxicillin, its Chinese medicine: floating and ratios other auxiliary material are 1: 0.1-1: 5.
6, slow releasing tablet according to claim 1 is characterized in that: additives include lubricant and filler, binding agent, disintegrating agent, lubricant, fluidizer and floating material and expanded material in the described slow releasing tablet.
7, intragastric floating sustained-release tablet agent according to claim 5 is characterized in that: the floating material of adding is hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, take off ethylene chitin, polyvinyl alcohol, octadecanol, hexadecanol, glycerol monostearate cheese, spermol, stearyl alcohol, stearic acid, Cera Flava.
8, intragastric floating sustained-release tablet agent according to claim 5 is characterized in that: the expanded material of adding is carbonate, bicarbonate or carbonate, bicarbonate and citric acid, tartaricly unites use.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100986302A CN101011363A (en) | 2005-09-26 | 2006-07-10 | Slow release tablet of amoxicillin |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510104989.1 | 2005-09-26 | ||
| CN 200510104989 CN1957928A (en) | 2005-09-26 | 2005-09-26 | Controlled release preparation of clinical treating medication, and fabricating method |
| CNA2006100986302A CN101011363A (en) | 2005-09-26 | 2006-07-10 | Slow release tablet of amoxicillin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101011363A true CN101011363A (en) | 2007-08-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006100986302A Pending CN101011363A (en) | 2005-09-26 | 2006-07-10 | Slow release tablet of amoxicillin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101011363A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103948555A (en) * | 2014-04-21 | 2014-07-30 | 海南海力制药有限公司 | Amoxicillin pulse sustained release tablet and preparation method thereof |
| CN106729658A (en) * | 2017-01-02 | 2017-05-31 | 武汉新联大生物有限公司 | A kind of amoxicillin solid dispersion and preparation method thereof |
| CN110354093A (en) * | 2019-07-31 | 2019-10-22 | 常州恒邦药业有限公司 | A kind of mosapride citrate pharmaceutical composition |
| CN113116860A (en) * | 2021-04-22 | 2021-07-16 | 海南通用三洋药业有限公司 | Amoxicillin capsule and preparation method thereof |
-
2006
- 2006-07-10 CN CNA2006100986302A patent/CN101011363A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103948555A (en) * | 2014-04-21 | 2014-07-30 | 海南海力制药有限公司 | Amoxicillin pulse sustained release tablet and preparation method thereof |
| CN106729658A (en) * | 2017-01-02 | 2017-05-31 | 武汉新联大生物有限公司 | A kind of amoxicillin solid dispersion and preparation method thereof |
| CN110354093A (en) * | 2019-07-31 | 2019-10-22 | 常州恒邦药业有限公司 | A kind of mosapride citrate pharmaceutical composition |
| CN110354093B (en) * | 2019-07-31 | 2021-09-17 | 常州恒邦药业有限公司 | Mosapride citrate pharmaceutical composition |
| CN113116860A (en) * | 2021-04-22 | 2021-07-16 | 海南通用三洋药业有限公司 | Amoxicillin capsule and preparation method thereof |
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