CN104095875A - Famotidine calcium magnesium chewable tablet - Google Patents
Famotidine calcium magnesium chewable tablet Download PDFInfo
- Publication number
- CN104095875A CN104095875A CN201410377785.4A CN201410377785A CN104095875A CN 104095875 A CN104095875 A CN 104095875A CN 201410377785 A CN201410377785 A CN 201410377785A CN 104095875 A CN104095875 A CN 104095875A
- Authority
- CN
- China
- Prior art keywords
- weight portions
- famotidine
- chewable tablet
- tablet
- calcium magnesium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 title claims abstract description 193
- 229960001596 famotidine Drugs 0.000 title claims abstract description 191
- 239000007910 chewable tablet Substances 0.000 title claims abstract description 125
- 229940068682 chewable tablet Drugs 0.000 title claims abstract description 125
- ZFXVRMSLJDYJCH-UHFFFAOYSA-N calcium magnesium Chemical compound [Mg].[Ca] ZFXVRMSLJDYJCH-UHFFFAOYSA-N 0.000 title claims abstract description 103
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 81
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- 239000000347 magnesium hydroxide Substances 0.000 claims abstract description 31
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims abstract description 31
- 150000001875 compounds Chemical class 0.000 claims abstract description 27
- 239000003826 tablet Substances 0.000 claims description 120
- 238000000034 method Methods 0.000 claims description 83
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 34
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- GVBFBKODLPVQOA-UHFFFAOYSA-N heptane-1-sulfonic acid;sodium Chemical compound [Na].CCCCCCCS(O)(=O)=O GVBFBKODLPVQOA-UHFFFAOYSA-N 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
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- 229940080428 lactose 200 mg Drugs 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 230000002475 laxative effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229940095489 magnesium hydroxide 150 mg Drugs 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
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- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
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- 210000004379 membrane Anatomy 0.000 description 1
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- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
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- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
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- 229940111202 pepsin Drugs 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
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- 229940085605 saccharin sodium Drugs 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
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- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- REFMEZARFCPESH-UHFFFAOYSA-M sodium;heptane-1-sulfonate Chemical compound [Na+].CCCCCCCS([O-])(=O)=O REFMEZARFCPESH-UHFFFAOYSA-M 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a famotidine calcium magnesium chewable tablet. The famotidine calcium magnesium chewable tablet contains famotidine, calcium carbonate and magnesium hydroxide. In particular, the invention belongs to the technical field of medicine, and relates to a medicinal composition for treating stomach disease, in particular to a compound medicinal composition of famotidine, calcium carbonate and magnesium hydroxide, in particular to a famotidine calcium magnesium chewable tablet which has superior medicinal property and contains famotidine, calcium carbonate and magnesium hydroxide. The famotidine calcium magnesium chewable tablet has superior pharmaceutical property and superior chemical stability. The famotidine calcium magnesium chewable tablet can be clinically used for treating or preventing acid regurgitation, gastric acid, heartburn (stomach burning), stomachache, stomach distension, belching and other stomach discomfort. A preparation method of the famotidine calcium magnesium chewable tablet is further related.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of pharmaceutical composition that is used for the treatment of gastropathy, the compound medicament composition that particularly relates to famotidine (Famotidine), calcium carbonate, magnesium hydroxide, more particularly relates to a kind of famotidine calcium magnesium chewable tablet that comprises famotidine, calcium carbonate, magnesium hydroxide with good pharmaceutical properties.Famotidine calcium magnesium chewable tablet of the present invention not only has good galenic pharmacy character, and has good chemical stability.Famotidine calcium magnesium chewable tablet of the present invention can be used for treatment or the prevention of acid regurgitation, gastric acid, heartburn (heartburn), stomachache, flatulence, belch and other stomach discomfort clinically.
Background technology
Gastropathy is very common illness, the stomach discomfort symptom such as conventionally have epigastric discomfort, stomachache or burn feeling, heartburn sense, abdominal distention during outbreak, feel sick.According to interrelated data, show; the external sickness rate of digestive system disease is in 20% left and right; China's sickness rate approximately 30%; this greatly affects the normal study and work of people; therefore; protect the stomach of oneself, prevent that the generation of gastropathy or recurrence from having very important meaning to maintenance people normal quality of life.
Generation and the gastric acid of gastropathy have close relationship, and gastric acid is that the parietal cell by gastric mucosa secretes, and has several functions: activate pepsinogen, impel it to be converted into pepsin, this kind of enzyme energy aminosal, is beneficial to decomposition and the absorption of small intestinal; Kill with food and enter the antibacterial of gastric in order to avoid human body is worked the mischief; Promote small intestinal to absorb ferrum and calcium system, lack for a long time gastric acid and can cause iron deficiency anemia and low blood calcium; Gastric acid enters after small intestinal, can promote the secretion of pancreatic juice, intestinal juice and bile.Although gastric acid has very important effect in digestive system, too much gastric acid can cause certain harm to human body.
Clinical studies show, because hyperchlorhydria generates, or gastric acid to the place that should not go (as gastroesophageal reflux) be the basic reason that gastropathy occurs.Certainly, although also there is the growing amount of people's gastric acid not increase, owing to there being gastric acid excretory function obstacle, make gastric acid overstand, or because body is strong to sour sensitivity, make reality and the gastric acid exceeded produces and stimulates stomach, thereby produce various malaise symptoms.So controlling gastric acid is the key of protecting stomach.The patient of hyperchlorhydria, due to the stimulation of gastric acid, stomach has burn feeling, the heartburn symptom of as the saying goes, this is chest interruption or the rest pain that backflows and cause into esophagus due to gastric acid, conventionally betides night.
The medicine that acts on gastric acid on market mainly contains two large classes: a class is antacid, directly in and gastric acid, conventional medicine (containing compound preparation) has aluminium hydroxide, calcium carbonate, magnesium oxide, magnesium trisilicate, aluminium silicate, aluminum phosphate, aluminum magnesium hydroxide etc.An other class is acid inhibitor, and the performance effect of effecting a permanent cure acts on slowlyer, in not participating in directly and gastric acid, mainly contains H
2receptor antagonist is as cimetidine, ranitidine and famotidine etc., and this class drug potency is larger, is mainly used in the treatment of the serious gastroenteropathys such as gastric ulcer.
2000, Johnson & Johnson-Merck & Co., Inc. has released the heartburn and dyspeptic Pepcid Complete of the gastroxia type chewable tablet that is used for the treatment of through FDA approval, this chewable tablet is nonprescription drugs, by 10mg famotidine, 800mg calcium carbonate and 165mg magnesium hydroxide, formed, that first is also unique complete inhibitor of the gastric acid that integrates long-acting and fugitive gastric acid drugs with function in the world, thereby fundamentally overcome independent use antacid can only be temporarily in and gastric acid, and antacid needs certain hour could start the contradiction situation of onset.This chewable tablet has following several feature: 1, effect rapidly, rapid taking after in and gastric acid, relief of symptoms.2, long-acting, take rear gastric acid secretion inhibiting and can reach more than 12 hours.3, easy to use, only take a slice and can deal with problems.4, provide two kinds of mechanism of action, both gastric acid secretion inhibitings, again can be immediately in and gastric acid.
Pepcid Complete be a kind of both can quick acting, the heartburn complex for the treatment of that can keep symptom not recur again.Before this medicine, approximately 100,000,000, having in the American of burn feeling symptom more, most people has been used more than one agents alleviate symptom, they should consider that quick acting considers duration of efficacy again, now with Pepcid Complete just without being used alternatingly other medicines, consumer only takes a slice and just can kill two birds with one stone, and both can prove effective fast, can maintain the longer time again.
Director Michael doctor of medicine Wolfe of the gastrointestinal disease department of the Chinese Academy of Sciences of Boston medical college, medical center, Boston University explains: nothing can control gastric acid quickly than Pepcid Complete, in addition, do not have other medicines than Pepcid Complete, to there is the effect of stronger prevention burn feeling and the dyspeptic recurrence of gastroxia type yet.
Pepcid Complete chewable tablet, containing 10mg famotidine, is the third generation H occurring after cimetidine and ranitidine
2receptor antagonist.Famotidine was developed by Japanese Yamanouchi (Yamanoouchi) Pharmaceutical Co., Ltd in 1981, within 1985, produced and went on the market, and applied at present in 60Duo Ge countries and regions, the world.Large 32 times than cimetidine of the action intensities of famotidine, large 9 times than ranitidine, action time is also than cimetidine and ranitidine long 1/3.H on famotidine energy blocking histamine and parietal cell film
2receptors bind, thereby the gastric acid secretion that dosage correlation ground suppresses basal gastric acid secretion and stimulated by food, pentagastrin, histamine, insulin and caffeine.Take 20 evening, after 40mg famotidine, the secretion of gastric acid respectively suppressed 86% and 94%, takes 20 morning, 40mg famotidine is after 3 ~ 5 hours, the secretion of gastric acid is 25% and 30% after suppressed 76% and 84%, 8 ~ 10 hour respectively.In this product, the acid of famotidine Sustainable Control reaches 12 hours.
The oral rear incomplete absorption of famotidine, reaches blood medicine peak value for 2～3 hours, t
1/2be about 3 hours.Famotidine extensively distributes in vivo, has high concentration to distribute, but do not see through placental barrier at digestive tract, kidney, liver, submaxillary gland and pancreas, and oral administration biaavailability is about 40 ~ 45%, and plasma protein binding rate is 15 ~ 20%.The removing half-life of famotidine is 2.5 ~ 3.5 hours, and 65 ~ 70% dosage is by renal excretion, and kidney clearing amount is 250 ~ 450ml/min, and 25 ~ 30% come across in urine with prototype.The bile excretion amount of famotidine is few, can in milk, discharge.In addition, removing half-life and the kidney clearing amount of famotidine have substantial connection, and kidney clearing amount <10ml/min patient's the removing half-life will be extended down to more than 20 hours.
In this compound recipe chewable tablet, containing calcium carbonate 800mg, calcium carbonate is the very common medicine for gastroenteropathy treatment of an external class, and it has good efficacy and saferry.Domestic at present existing Duo Jia pharmaceutical factory produces calcium carbonate, for replenishing the calcium or antacid.Calcium carbonate can in and gastric acid, to gastric acid secretion, without direct repression, be mainly to eliminate gastric acid the feedback of parietal cell secretion is suppressed by improving gastric acid pH, concrete mechanism of action is: 1, and H
+, reduce H
+back diffusion to gastric mucosa; 2, improve gastric juice pH, reduce gastric acid and pepsic activity.
After calcium carbonate is taken, be combined generate the calcium chloride of ease of solubility at gastric with hydrochloric acid, inferior carbonic acid effect in 90% calcium chloride and small intestinal forms insoluble calcium salt, and the calcium chloride of residue 10% is absorbed after being combined with inferior carbonic acid and enters body and circulate.Calcium carbonate is mainly by intestinal absorption, at alkaline intestinal juice or while having abundant fatty acid to exist, easily forms calcium soap and reduces absorption.80% dosage is from defecate, and 20% from urine excretion.With under empty stomach condition, take calcium carbonate and compare, 1 hour after the meal or sleep before take it to act on the lasting time longer.
This compound recipe chewable tablet also contains magnesium hydroxide 165mg, and its antiacid effect is strong compared with sodium bicarbonate, in and gastric acid effect slowly and lasting, do not produce carbon dioxide.Take rear and gastric acid effect generation solubility chlorination magnesium, emit magnesium ion, magnesium ion stimulating gastrointestinal is wriggled, and has laxative effective, is applicable to the hyperchlorhydria with constipation; For not accompanying constipation person, this product is seldom as single antiacid drug use, and general and calcium carbonate share to eliminate its hypocatharsis effect.
Magnesium hydroxide is non-systemic antacid thing, has minute quantity to change solubility chlorination magnesium at gastric after taking, and a small amount of absorption discharged by kidney.
Controlled clinical trial shows, with other antiacid products or press down acid product and compare, Pepcid Complete chewable tablet has two large features: 1, rapid-action: after drug administration 30 minutes, the burn feeling remission rate of Pepcid Complete chewable tablet group (1205), famotidine group (1229), antiacid medicine (calcium carbonate and magnesium hydroxide) (1212) and placebo group (1217) was respectively 45.3%, 37.8%, 40.9% and 33.0%.2, acting duration is long: drug administration is after 7 hours, and the remission rate of Pepcid Complete chewable tablet group, famotidine group, antiacid medicine (calcium carbonate and magnesium hydroxide) and placebo group is respectively 70.4%, 68.3%, 61.3% and 59.0%.
In above-mentioned compound recipe chewable tablet, in view of the amount of every middle calcium carbonate up to the amount of 800mg and magnesium hydroxide up to 165mg, and amount only have famotidine 10mg, and the chemical stability of famotidine is relatively responsive, therefore, prepare this compound recipe chewable tablet and have many technical difficulties.
Therefore, famotidine/calcium carbonate/magnesium hydroxide compound preparation that advantageous property is still expected to have in this area is its chewable tablet for example, expects that this chewable tablet not only has good preparation performance but also has good stability for example especially.
Summary of the invention
The object of the present invention is to provide for example its chewable tablet of a kind of famotidine/calcium carbonate/magnesium hydroxide compound preparation with advantageous property, expect that this chewable tablet has good preparation performance and/or has good stability for example especially.The present invention have been surprisingly found that, famotidine/calcium carbonate/magnesium hydroxide compound recipe chewable tablet with feature of the present invention has good preparation performance and/or has good stability, the present invention is based on this discovery and is accomplished.
For this reason, first aspect present invention provides a kind of famotidine calcium magnesium chewable tablet, wherein comprises famotidine, calcium carbonate, magnesium hydroxide.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein comprise famotidine 10 weight portions, calcium carbonate 750 ~ 850 weight portions (780 ~ 820 weight portions for example, approximately 800 weight portions for example), magnesium hydroxide 150 ~ 180 weight portions (for example 155 ~ 175 weight portions, for example approximately 165 weight portions).
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises sorbitol.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount of sorbitol is 10 ~ 100 weight portions, for example 20 ~ 80 weight portions, for example 30 ~ 70 weight portions.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises Sucralose.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount of Sucralose is 1 ~ 20 weight portion, for example 2 ~ 15 weight portions, for example 3 ~ 10 weight portions.Have been surprisingly found that, when making after the sorbitol of famotidine and abundant amount fully mixes in other material that adds again this tablet to together with Sucralose, famotidine in gained tablet has significantly good chemical stability, but when sorbitol consumption is excessive, can cause the new problem of tablet friability deficiency.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein said sorbitol and Sucralose are after fully mixing together with famotidine, to add in other material of this tablet again.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises lactose.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount of lactose is 25 ~ 250 weight portions, for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises starch.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount of starch is 25 ~ 250 weight portions, for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises cane sugar powder.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount of cane sugar powder is 200 ~ 500 weight portions, for example 250 ~ 450 weight portions, for example 300 ~ 400 weight portions.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises aluminum color lake.In one embodiment, described aluminum color lake can be Ponceau 4R aluminum lake.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount in aluminum color lake is 0.1 ~ 1 weight portion, for example 0.2 ~ 0.75 weight portion, for example 0.3 ~ 0.7 weight portion.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises Oleum menthae.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount of Oleum menthae is 1 ~ 15 weight portion, for example 2 ~ 12 weight portions, for example 2 ~ 8 weight portions, for example 2 ~ 6 weight portions.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises essence.In one embodiment, described essence can be flavoring orange essence.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount of essence is 1 ~ 15 weight portion, for example 2 ~ 12 weight portions, for example 3 ~ 8 weight portions, for example 4 ~ 6 weight portions.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises
magnesium stearate.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, for the famotidine of every 10 weight portions, wherein the amount of magnesium stearate is 10 ~ 50 weight portions, for example 20 ~ 40 weight portions.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein also comprises polyvidone.In one embodiment, described polyvidone is PVP K-30,30 POVIDONE K 30 BP/USP-15 or 30 POVIDONE K 30 BP/USP-60.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein said polyvidone is to add as the consumption of binding agent.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein said polyvidone is that water is mixed with the consumption as binding agent after the solution of concentration 8 ~ 12% and adds.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, it has the contact angle that is less than 110 °, and for example it has the contact angle that is less than 100 °, for example, have the contact angle that is less than 90 °, for example the contact angle of 40 ~ 90 °, particularly has the contact angle of 40 ~ 85 °.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein said calcium carbonate, magnesium hydroxide are after mixing homogeneously with cane sugar powder three, under relative humidity 85% humid air stream poker part, mix after at least 5 hours again, then prepare with other mixing of materials that tablet uses and join in described tablet.Have been surprisingly found that, if calcium carbonate, magnesium hydroxide do not carry out above-mentioned mixing under relative humidity 85% humid air stream poker part, or when the incorporation time under this relative humidity 85% humid air stream poker part is not enough, the contact angle of prepared tablet is all greater than 95 °; Have been found that, uniformity of dosage units for low content medicine famotidine, contact angle is less than the tablet that the material of 90 ° suppresses and has extremely good uniformity of dosage units, and be greater than after 95 ° when the contact angle of material, the famotidine uniformity of dosage units of the tablet of this material compacting mostly just can reach the acceptable limit of pharmacopeia or even defective.
Contact angle described herein refers to the contact angle with water.Particularly, contact angle refers to and drips the angle contacting with compositions surface in the water droplet on the solid preparation compositions surfaces such as tablet.Those skilled in the art know the method and apparatus that has many mensuration contact angles, and in the present invention, an exemplary assay method is as follows: at syringe needle, (for example model is SNSO52/026; HAMILTON company produces, stainless steel, internal diameter 0.26mm, external diameter 0.52mm; Or the also available syringe needle with similar specification) needle point forms 1 μ l pure water (MILLI-Q; MILLIPORE company) drop, more for example, by contact angle determination device (OCA-15 type, Data physics company; Or the contact angle determination device with other brand or the model of similar functions) measure water droplet and be added to the contact angle after 60 milliseconds of tablet surface.When tablet surface has curvature, measure again contact angle after will proofreading and correct as straight line when resolving; Normally under room temperature, measure.In the present invention, if not otherwise indicated, contact angle of the present invention is measured by following methods: at room temperature, and at syringe needle (SNSO52/026; HAMILTON company produces, stainless steel, internal diameter 0.26mm, external diameter 0.52mm) needle point form 1 μ l pure water (MILLI-Q; MILLIPORE company) drop, then by contact angle determination device (OCA-15 type, Data physics company), measure water droplet and be added to the contact angle after 60 milliseconds of tablet surface.Owing to measuring the contact angle obtaining with above-mentioned conditions of similarity, for example, for example, at varying environment (different experiments chamber), distinct device (the contact angle determination device that uses other company to produce), these results do not have obvious difference, therefore when the contact angle of definition compositions of the present invention, without concrete mensuration process and condition determination to contact angle, be construed as limiting.
For the solid preparation that is not tablet, such as capsule, granule, powder etc., or the final mixture material of chewable tablet of the present invention before tabletting, can be by the powder containing in preparation, granule, semi-solid material etc. be pressed into figure of tablet, measure again, for example, for capsule, can be by taking out capsule 's content, get wherein that about 200mg is pressed into having an even surface of diameter 8mm, thickness 3.5mm and smooth tablet is measured contact angle.Even for the tablet that can not effectively reflect its real property, the tablet of film coating, enteric coating or sugar-coat for example, also can be by the clothing layer in tablet surface be scraped off, and then tablet is ground, refer again to the mode of above-mentioned capsule, tablet is ground after gained powder is suppressed in flakes again and measured.For the present composition, it is not suppressed when in blocks in preparation, can get the appropriate compacting of powder laggard row in blocks and measure; It,, when being prepared into the plain sheet of coating not, can directly be measured; It, can scrape off the clothing layer in tablet surface while making coated tablet coated, and then tablet is ground, then measures after gained powder is suppressed in flakes again.
Have been found that preparation has the material that the chewable tablet of the present invention of good famotidine uniformity of dosage units can have a low contact angle by acquisition and realizes.Although the present invention uses aforesaid way can reduce significantly the contact angle of chewable tablet material of the present invention, yet applicant believes and still has the contact angle that all multi-methods can reduce material, the method that obtains good famotidine uniformity of dosage units can realize by having the material of low contact angle as described herein, and is not limited to the above-mentioned processing mode to calcium carbonate, magnesium hydroxide and cane sugar powder three of the present invention.The famotidine calcium magnesium chewable tablet of the present invention limiting with this technical scheme of low contact angle will present good famotidine uniformity of dosage units effect.
Exemplary [contact angle test] is as follows:
Syringe needle: model is SNSO52/026; HAMILTON company produces, stainless steel, internal diameter 0.26mm, external diameter 0.52mm;
Pure water: MILLI-Q (MILLIPORE company product) pure water processed;
Contact angle determination device: CA-15 type, Data physics company produces;
Assay method: form 1 μ l pure water drop at needle point, measure it and drip to the contact angle behind 60 milliseconds, compacting surface in blocks.
Sample pretreating: the material before tabletting is first pressed into plane tablet; Compressing tablet is directly measured, but when calculating, the curvature of tablet surface is proofreaied and correct; For coated sheet, clothing layer is struck off completely, then be ground into fine powder, and then be pressed into plane tablet.
At each example below, for each batch sample, its final hybrid particles before tabletting, suppress chewable tablet in blocks, two kinds of contact angles basic identical (differ and be no more than 3 °) that sample records.The sample of embodiment 1 for example, final hybrid particles, suppresses the two contact angle recording of chewable tablet in blocks and is respectively 73 °, 71 °.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, wherein comprises:
Famotidine 10 weight portions,
Calcium carbonate 750 ~ 850 weight portions (for example 780 ~ 820 weight portions, for example approximately 800 weight portions),
Magnesium hydroxide 150 ~ 180 weight portions (for example 155 ~ 175 weight portions, for example approximately 165 weight portions),
Sorbitol 10 ~ 100 weight portions (for example 20 ~ 80 weight portions, for example 30 ~ 70 weight portions),
Sucralose 1 ~ 20 weight portion (for example 2 ~ 15 weight portions, for example 3 ~ 10 weight portions),
Lactose 25 ~ 250 weight portions (for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions),
Starch 25 ~ 250 weight portions (for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions),
Cane sugar powder 200 ~ 500 weight portions (for example 250 ~ 450 weight portions, for example 300 ~ 400 weight portions),
Aluminum color lake 0.1 ~ 1 weight portion (for example 0.2 ~ 0.75 weight portion, for example 0.3 ~ 0.7 weight portion),
Oleum menthae 1 ~ 15 weight portion (for example 2 ~ 12 weight portions, for example 2 ~ 8 weight portions, for example 2 ~ 6 weight portions),
The amount of essence be 1 ~ 15 weight portion (for example 2 ~ 12 weight portions, for example 3 ~ 8 weight portions, for example 4 ~ 6 weight portions),
The amount of magnesium stearate is 10 ~ 50 weight portions, for example 20 ~ 40 weight portions and
Appropriate polyvidone.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, it is under the condition of packing, be placed under 40 ° of C, lucifuge condition and place 6 months, this famotidine calcium magnesium chewable tablet residual content (%) during June of the relative amount (%) during with respect to 0 month when June is greater than 95%, being for example 95% ~ 102%, for example, is 96% ~ 101%.
The famotidine calcium magnesium chewable tablet providing according to the arbitrary embodiment of first aspect present invention, it is under the condition of packing, be placed under 40 ° of C, lucifuge condition and place 6 months, this famotidine calcium magnesium chewable tablet impurity A when June increases percentage amounts (%) and is less than 75%, be for example 20 ~ 100%, being for example 30 ~ 80%, for example, is 30 ~ 75%.
Further, second aspect present invention provides a kind of method of preparing famotidine calcium magnesium chewable tablet.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said for not comprising famotidine, calcium carbonate, magnesium hydroxide in fourth calcium magnesium chewable tablet.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said for example, for comprising famotidine 10 weight portions, calcium carbonate 750 ~ 850 weight portions (780 ~ 820 weight portions in fourth calcium magnesium chewable tablet, approximately 800 weight portions for example), magnesium hydroxide 150 ~ 180 weight portions (for example 155 ~ 175 weight portions, for example approximately 165 weight portions).
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said for also not comprising sorbitol in fourth calcium magnesium chewable tablet.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount of sorbitol is 10 ~ 100 weight portions, for example 20 ~ 80 weight portions, for example 30 ~ 70 weight portions.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise Sucralose.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount of Sucralose is 1 ~ 20 weight portion, for example 2 ~ 15 weight portions, for example 3 ~ 10 weight portions.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said in fourth calcium magnesium chewable tablet, described sorbitol adds to after being fully to mix together with famotidine with Sucralose in other material of this tablet again.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise lactose.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount of lactose is 25 ~ 250 weight portions, for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise starch.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount of starch is 25 ~ 250 weight portions, for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise cane sugar powder.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount of cane sugar powder is 200 ~ 500 weight portions, for example 250 ~ 450 weight portions, for example 300 ~ 400 weight portions.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise aluminum color lake.In one embodiment, described aluminum color lake can be Ponceau 4R aluminum lake.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount in aluminum color lake is 0.1 ~ 1 weight portion, for example 0.2 ~ 0.75 weight portion, for example 0.3 ~ 0.7 weight portion.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise Oleum menthae.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount of Oleum menthae is 1 ~ 15 weight portion, for example 2 ~ 12 weight portions, for example 2 ~ 8 weight portions, for example 2 ~ 6 weight portions.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise essence.In one embodiment, described essence can be flavoring orange essence.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount of essence is 1 ~ 15 weight portion, for example 2 ~ 12 weight portions, for example 3 ~ 8 weight portions, for example 4 ~ 6 weight portions.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise magnesium stearate.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, for the famotidine of every 10 weight portions, wherein the amount of magnesium stearate is 10 ~ 50 weight portions, for example 20 ~ 40 weight portions.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, also comprise polyvidone.In one embodiment, described polyvidone is PVP K-30,30 POVIDONE K 30 BP/USP-15 or 30 POVIDONE K 30 BP/USP-60.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said in fourth calcium magnesium chewable tablet, described polyvidone is that the consumption as binding agent adds.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, described polyvidone is that water is mixed with the consumption as binding agent after the solution of concentration 8 ~ 12% and adds, and because being adopts wet granulation, those skilled in the art do not do clearly restriction to the concrete consumption of binding agent conventionally, and just conventionally rule of thumb reach and obtain satisfied granule.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said do not have for fourth calcium magnesium chewable tablet the contact angle that is less than 110 °, for example it has the contact angle that is less than 100 °, for example there is the contact angle that is less than 90 °, for example the contact angle of 40 ~ 90 °, particularly has the contact angle of 40 ~ 85 °.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, described calcium carbonate, magnesium hydroxide are after mixing homogeneously with cane sugar powder three, under relative humidity 85% humid air stream poker part, mix after at least 5 hours again, then prepare with other mixing of materials that tablet uses and join in described tablet.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said not in fourth calcium magnesium chewable tablet, comprise:
Famotidine 10 weight portions,
Calcium carbonate 750 ~ 850 weight portions (for example 780 ~ 820 weight portions, for example approximately 800 weight portions),
Magnesium hydroxide 150 ~ 180 weight portions (for example 155 ~ 175 weight portions, for example approximately 165 weight portions),
Sorbitol 10 ~ 100 weight portions (for example 20 ~ 80 weight portions, for example 30 ~ 70 weight portions),
Sucralose 1 ~ 20 weight portion (for example 2 ~ 15 weight portions, for example 3 ~ 10 weight portions),
Aluminum color lake 0.1 ~ 1 weight portion (for example 0.2 ~ 0.75 weight portion, for example 0.3 ~ 0.7 weight portion),
Lactose 25 ~ 250 weight portions (for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions),
Cane sugar powder 200 ~ 500 weight portions (for example 250 ~ 450 weight portions, for example 300 ~ 400 weight portions),
Oleum menthae 1 ~ 15 weight portion (for example 2 ~ 12 weight portions, for example 2 ~ 8 weight portions, for example 2 ~ 6 weight portions),
Starch 25 ~ 250 weight portions (for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions),
The amount of essence be 1 ~ 15 weight portion (for example 2 ~ 12 weight portions, for example 3 ~ 8 weight portions, for example 4 ~ 6 weight portions),
The amount of magnesium stearate is 10 ~ 50 weight portions, for example 20 ~ 40 weight portions and
Appropriate polyvidone.
The method providing according to the arbitrary embodiment of second aspect present invention, wherein said have the feature described in the arbitrary embodiment of first aspect present invention for fourth calcium magnesium chewable tablet.
The method providing according to the arbitrary embodiment of second aspect present invention, it comprises the following steps:
(1) povidone solution that compound concentration is 8 ~ 12%, standby;
(2) each solid material is pulverized respectively, crossed 120 mesh sieves;
(3) get Oleum menthae, the starch mix homogeneously of recipe quantity, place one day, standby;
(4) famotidine, Sucralose, sorbitol three of getting recipe quantity be mix homogeneously fully, standby;
(5) cane sugar powder, calcium carbonate, magnesium hydroxide of getting recipe quantity be mix homogeneously fully, then mixes at least 5 hours under relative humidity 85% humid air stream poker part, standby;
(6) get aluminum color lake and the lactose mix homogeneously of recipe quantity, standby;
(7) by above step (4) ~ (6) gained material mix homogeneously, by step (1) gained povidone solution, be binding agent, wet granulation, transfers to gained wet granular in air dry oven 60 ~ 80
odry 2 ~ 4 hours of C, granulate, obtains dry granule;
(8) by step (3) gained mixture and the dry granule of step (7) gained and the magnesium stearate of recipe quantity, the essence of recipe quantity is mixed homogeneously, obtain eventually mixed granule;
(9), by the every specification containing famotidine 10mg, by the eventually mixed granule tabletting on tablet agent of step (8) gained, obtain famotidine calcium magnesium chewable tablet.
The method providing according to the arbitrary embodiment of second aspect present invention, the wherein said fourth calcium magnesium chewable tablet that do not replace is under the condition of packing, be placed under 40 ° of C, lucifuge condition and place 6 months, this famotidine calcium magnesium chewable tablet residual content (%) during June of the relative amount (%) during with respect to 0 month when June is greater than 95%, being for example 95% ~ 102%, for example, is 96% ~ 101%.
The method providing according to the arbitrary embodiment of second aspect present invention, the wherein said fourth calcium magnesium chewable tablet that do not replace is under the condition of packing, be placed under 40 ° of C, lucifuge condition and place 6 months, this famotidine calcium magnesium chewable tablet impurity A when June increases percentage amounts (%) and is less than 75%, be for example 20 ~ 100%, being for example 30 ~ 80%, for example, is 30 ~ 75%.
In the step of the above-mentioned preparation method of the present invention, although the step of the concrete steps of its description in some details or described in the preparation example of language description up and down literary composition specific embodiment part distinguished to some extent, yet the open in detail of those skilled in the art's full text according to the present invention can summarize the above method step completely.
Arbitrary embodiment of either side of the present invention, can combine with other embodiment, as long as they there will not be contradiction.In addition, in arbitrary embodiment of either side of the present invention, arbitrary technical characterictic goes for this technical characterictic in other embodiment, as long as they there will not be contradiction.Below the invention will be further described.
All documents that the present invention quotes from, their full content is incorporated to herein by reference, and if when the expressed implication of these documents and the present invention are inconsistent, be as the criterion with statement of the present invention.In addition, various terms and phrase that the present invention uses have the general sense of well known to a person skilled in the art, nonetheless, the present invention still wishes at this, these terms and phrase to be described in more detail and to be explained, the term of mentioning and phrase, if any inconsistent with known implication, are as the criterion with the implication that the present invention was explained.
In the present invention, famotidine calcium magnesium chewable tablet of the present invention also can be described as compound famotidine chewing tablet or other similar appellation.
The contained main composition famotidine of this product famotidine calcium magnesium chewable tablet is the third generation H occurring after cimetidine and ranitidine
2receptor antagonist, large 32 times than cimetidine of its action intensities, large 9 times than ranitidine, action time is also than cimetidine and ranitidine long 1/3.H on famotidine energy blocking histamine and parietal cell film
2receptors bind, thereby the gastric acid secretion that dosage correlation ground suppresses basal gastric acid secretion and stimulated by food, pentagastrin, histamine, insulin and caffeine.Take 20 evening, after 40mg famotidine, the secretion of gastric acid respectively suppressed 86% and 94%, takes 20 morning, 40mg famotidine is after 3 ~ 5 hours, the secretion of gastric acid is 25% and 30% after suppressed 76% and 84%, 8 ~ 10 hour respectively.In this product, the acid of famotidine Sustainable Control reaches 12 hours.
Every of this product is containing calcium carbonate and magnesium hydroxide, these two kinds of compositions can in and gastric acid, to gastric acid secretion, without direct repression, be mainly to eliminate gastric acid the feedback of parietal cell secretion is suppressed by improving gastric acid pH, concrete mechanism of action is: 1, and H
+, reduce H
+back diffusion to gastric mucosa; 2, improve gastric juice pH, reduce gastric acid and pepsic activity.
Hydrogen-oxygen generally share to eliminate the hypocatharsis effect of magnesium for magnesium with calcium carbonate.
In the pharmacokinetics test of healthy volunteer's compound famotidine chewing tablet single dose administration that famotidine calcium magnesium chewable tablet of the present invention is carried out, measured compound famotidine chewing tablet main component famotidine through time blood concentration, calculate the main pharmacokinetic parameter of famotidine, understand absorption, distribution, the elimination rule of famotidine in human body, for compound famotidine chewing tablet II clinical trial phase provides testing program safely, effectively and reasonably.
10 of healthy volunteers, men and women half and half, respectively at test, on an empty stomach once takes 2 of compound famotidine chewing tablets morning on the same day, before medicine and after medicine 0.5,1.0,1.5,2,2.5,3,3.5,4,6,8, within 10,12,15 hours, get ulnar vein blood 4ml, put in anticoagulant heparin test tube, 3000 revs/min centrifugal 10 minutes, get blood plasma minute double in-20
0c stores standby survey.Famotidine blood concentration-time data is processed through the practical pharmacokinetics calculation procedure of < < DAS > >, obtains the pharmacokinetic parameter of famotidine.Result shows, the main pharmacokinetic parameter t of famotidine
1/2be 4.013 ± 0.332h, Tmax is 1.950 ± 0.284h, and Cmax is 63.597 ± 17.703 μ g/ml, AUC
0～15be 327.837 ± 73.647 μ g/mlh, AUC
0～∞be 394.937 ± 75.533 μ g/mlh, Ke is 0.174 ± 0.016h
-1, MRT is 6.552 ± 0.635h.Show that in compound famotidine chewing tablet, oral approximately 2 h of famotidine reach blood concentration peak value, on average eliminate half-life 4 h, basically identical with bibliographical information.In preparation, other compositions do not affect its physiological disposition.
In the multiple center clinical study that famotidine calcium magnesium chewable tablet of the present invention is carried out, evaluated that compound famotidine chewing tablet alleviates that acid-related disease (peptic ulcer, gastroesophageal reflux disease (GERD), reflux esophagitis, chronic gastritis etc.) causes heartburn, return clinical efficacy and the safety thereof of the symptoms such as acid, stomachache, and compare with famotidine tablets.
Main validity evaluation index comprises: paresthesia alleviateding time after clinical symptoms total points, first dose.The time that the symptoms such as heartburn after paresthesia alleviateding time after the first dose=first day of taking medicine (first dose) medication, acid regurgitation are alleviated completely, according to the judgement of patient's diary card record.
Administrated method: be 7 days the whole course for the treatment of.When test group first day has symptom, first famotidine simulation sheet is 1, after take 1 of compound famotidine chewing tablet, second day and taking medicine (method of administration and dosage are the same) while having symptom in several days subsequently, if asymptomatic, takes medicine before sleeping.When matched group first day has symptom, first famotidine sheet is 1, after take 1 of compound famotidine chewing tablet simulation sheet, second day and taking medicine (method of administration and dosage are the same) while having symptom in several days subsequently, if asymptomatic, takes medicine before sleeping.
Result demonstration, compound famotidine chewing tablet of the present invention reaches more than 95% at effective percentage aspect the treatment for acid regurgitation, gastric acid, heartburn (heartburn), stomachache, flatulence, belch and other stomach discomfort or prevention, and untoward reaction rate is extremely low.
The specific embodiment
By the following examples, can conduct further description the present invention, yet scope of the present invention is not limited to following embodiment.One of skill in the art can understand, and is not deviating under the prerequisite of the spirit and scope of the present invention, can carry out various variations and modification to the present invention.The present invention carries out generality and/or concrete description to the material and the test method that use in test.Although be well known in the art for realizing many materials and the operational approach that the object of the invention used, the present invention still does to describe in detail as far as possible at this.
The below object of preparation process in order to give an example, and the comparability based on respectively giving an example and making some specific description, those skilled in the art can therefrom summarize the method that the present invention prepares aqueous injection that obtains completely according to existing knowledge.In the various chewable tablet compositionss of preparation, if not otherwise indicated, total dosage of every batch is 50,000 amounts below, in every containing famotidine 10mg.When listing formula and preparation process, for various tablets, with the composition in every 1, illustrate formula and method for making.Below prepare in the example of compositions, if not otherwise indicated, various materials are all pulverized before use and can be by 120 mesh sieve.
one, method of testing
famotidine assay in test case 1, tablet
According to 2010 editions two appendix V D high effective liquid chromatography for measuring of Chinese Pharmacopoeia;
Chromatographic condition and system suitability: with octadecylsilane chemically bonded silica, be filler; With heptanesulfonic acid sodium solution (get sodium heptanesulfonate 2.0g, add after water 900ml dissolving, regulate pH value to 3.9 with glacial acetic acid, add water to 1000ml)-acetonitrile-methanol (25:6:1), be mobile phase; Detection wavelength is 254nm; Number of theoretical plate calculates and should be not less than 2000 by famotidine peak;
Algoscopy: the sample that the weight differential of learning from else's experience is measured, porphyrize, precision takes in right amount (being approximately equivalent to famotidine 10mg), put in 50ml measuring bottle, add methanol appropriate, jolting is dissolved famotidine, and be diluted to scale with methanol, and shake up, filter, precision measures subsequent filtrate 1ml, puts in 10ml measuring bottle, by mobile phase, is diluted to scale, shake up, filter, as need testing solution, measure 20 μ l injection liquid chromatographies, record chromatogram; The phosphorus pentoxide 80o С drying under reduced pressure famotidine reference substance of 4 hours of separately learning from else's experience is appropriate, is measured in the same method; By external standard method with calculated by peak area, the famotidine (C in every
8h
15n
7o
2s
3) content.
famotidine Determination of Content Uniformity in test case 2, tablet
According to the famotidine determination in the tablet of method shown in 2010 editions two appendix X E of Chinese Pharmacopoeia and above-mentioned test case 1, measure each time and test the famotidine uniformity of dosage units in preparation-obtained compound famotidine chewing tablet.Generally speaking, pharmacopeia regulation, A+1.80S≤15.0 are item qualified, if A+1.80S value is less, uniformity of dosage units is better; If A+1.80S>15.0 is defective.Certainly A+1.80S approaches at 15.0 o'clock, shows that preparation process is dangerous and has much room for improvement.
specific impurities inspection in test case 3, tablet
According to allied compound (Related compounds) detection method in 35 editions (USP35) the 3153rd page of contained famotidine tablets of American Pharmacopeia (Famotidine Tablets), check, especially severe is 3-[2-(diamino methylene is amino)-1 to the impurity A at relative retention time approximately 0.4 place wherein, 3-thiazole-4-yl methylsulfinyl]-N-sulfamoyl-the third amidine, be 3-[2-(diaminomethyleneamino)-1, 3-thiazol-4-ylmethylsulfinyl]-N-sulfamoyl-propanamidine, found that this impurity is the concern that needs that easily increase and normally special in preparation.
two, the embodiment 1 that prepared by tablet
embodiment 1: prepare famotidine calcium magnesium chewable tablet
Prescription:
Famotidine 10mg,
Calcium carbonate 800mg,
Magnesium hydroxide 165mg,
Sucralose 5mg,
Sorbitol 50mg,
Lactose 100mg,
Starch 110mg,
Ponceau 4R aluminum lake 0.5mg,
Cane sugar powder 356mg,
Oleum menthae 4mg,
PVP K-30 (10% solution) is appropriate,
Flavoring orange essence 5mg,
Magnesium stearate 30mg.
Method for making: each supplementary material is pulverized respectively, crosses 120 mesh sieves;
(1) preparation povidone solution, standby;
(2) each solid material is pulverized respectively, crossed 120 mesh sieves;
(3) get Oleum menthae, the starch mix homogeneously of recipe quantity, place one day, standby;
(4) famotidine, Sucralose, sorbitol three of getting recipe quantity be mix homogeneously fully, standby;
(5) cane sugar powder, calcium carbonate, magnesium hydroxide of getting recipe quantity be mix homogeneously fully, then mixes 6 hours under relative humidity 85% humid air stream poker part, standby;
(6) get aluminum color lake and the lactose mix homogeneously of recipe quantity, standby;
(7) by above step (4) ~ (6) gained material mix homogeneously, by step (1) gained povidone solution, be binding agent, wet granulation, transfers to gained wet granular in air dry oven 70
odry 3 hours of C, granulate, obtains dry granule;
(8) by step (3) gained mixture and the dry granule of step (7) gained and the magnesium stearate of recipe quantity, the essence of recipe quantity is mixed homogeneously, obtain eventually mixed granule;
(9) by the every specification containing famotidine 10mg, by the eventually mixed granule tabletting on tablet agent of step (8) gained, obtain famotidine calcium magnesium chewable tablet, this tablet sample is designated as Ex1.
supplement example 1:
Formula and method with reference to embodiment 1, different is only to change the amount of sorbitol wherein into 0mg, 10mg, 20mg, 30mg, 40mg, 60mg, 70mg, 80mg, 90mg, 120mg, obtain the tablet of 10 formulas, be designated as respectively B11, B12, B13, B14, B15, B16, B17, B18, B19, B10.These 10 batches of tablets carry out friability mensuration through tablet friability detection method shown in 2010 editions two appendix X G of Chinese Pharmacopoeia, result B18, B19, B10 are all greater than 1.2% by the excessive tablet less loss weight of sorbitol amount, exceeded pharmacopeia regulation and answered <1.0% and this area to it has been generally acknowledged that the good limit of <0.8%, this is worthless or even underproof.From this angle, it is worthless that the consumption of sorbitol surpasses 80mg/ sheet.
supplement example 2:
Formula and method with reference to embodiment 1, different is only to change the amount of Sucralose wherein into 0mg, 1mg, 2mg, 3mg, 6mg, 8mg, 10mg, 12mg, 15mg, 20mg, obtain the tablet of 10 formulas, be designated as respectively B21, B22, B23, B24, B25, B26, B27, B28, B29, B20.These 10 batches of tablets are through mouthfeel comparison, show that B21, B22, B23 three are more bitter, the very few bitterness that can not effectively cover famotidine of Sucralose consumption; B24, B25, B26, B27 mouthfeel are good, have covered the bitterness of famotidine completely; And B28, B29, B20 three cross the sweet bitter aftertaste sense that even has, this is the excessive reason of typical consumption.
supplement example 3:
With reference to B14, Ex1, tri-samples of B17, different is only that Sucralose is wherein replaced with to another kind of sweeting agent aspartame, obtains three samples and is designated as respectively B31, B32, B33.
With reference to B14, Ex1, tri-samples of B17, different is only that Sucralose is wherein replaced with to another kind of sweeting agent saccharin sodium, obtains three samples and is designated as respectively B34, B35, B36.
With reference to B14, Ex1, tri-samples of B17, different is only that Sucralose is wherein replaced with to another kind of sweeting agent An Saimi, obtains three samples and is designated as respectively B37, B38, B39.
supplement example 4:
With reference to B24, Ex1, tri-samples of B27, different is only that sorbitol is wherein replaced with to another kind of similar adjuvant mannitol, obtains three samples and is designated as respectively B41, B42, B43.
With reference to B24, Ex1, tri-samples of B27, different is only that sorbitol is wherein replaced with to another kind of similar adjuvant lactose, obtains three samples and is designated as respectively B44, B45, B46.
With reference to B24, Ex1, tri-samples of B27, different is only that sorbitol is wherein replaced with to another kind of similar adjuvant sucrose, obtains three samples and is designated as respectively B47, B48, B49.
supplement example 5:
With reference to formula and the method for embodiment 1, different is only that each mixing of materials of each material of step (4) and step (3) evenly and according to step (3) mode is processed and obtained mixture, and the tablet obtaining is thus designated as B51.
With reference to formula and the method for embodiment 1, different is only that each mixing of materials of each material of step (4) and step (5) evenly and according to step (5) mode is processed and obtained mixture, and the tablet obtaining is thus designated as B52.
With reference to formula and the method for embodiment 1, different is only that each mixing of materials of each material of step (4) and step (6) evenly and according to step (6) mode is processed and obtained mixture, and the tablet obtaining is thus designated as B53.
supplement example 6:
According to CN1456160A (03118638.6, Mao Youchang) technique one of description page 1 it ", the prescription of compound famotidine dispersible tablets form " and page 2 they preparation technology of compound famotidine dispersible tablets " two, " is prepared tablet (in the end during tabletting, with the every piezometric sheet containing famotidine 10mg), the tablet obtaining is thus designated as B61.
Formula and method for making according to CN1634045A (200310122940.X, Xinyi) description embodiment 5 are prepared tablet, and formula and method for making that coating famotidine used shines embodiment 1 wherein obtain, and the tablet obtaining is thus designated as B62.
According to CN1768744A, (200510021853.4, Tai Huatang) formula of description embodiment 1 and method for making are prepared tablet (in the end during tabletting, with the every piezometric sheet containing famotidine 10mg), and the tablet obtaining is thus designated as B63.
Formula and method for making according to CN100450481A (200610085742.4, east is auspicious) description embodiment 7 are prepared tablet, and formula and method for making that famotidine cyclodextrin clathrate used shines embodiment 1 wherein obtain, and the tablet obtaining is thus designated as B64.
test example 1: the stability of investigating tablet of the present invention
Various samples above, use aluminum-plastic composite membrane for packing, be placed under 40 ° of C, lucifuge condition and place 6 months (in the present invention, the high-temperature treatment mode of this kind for its reserve temperature can be described as high temperature June, 40 ° of C6 months, high temperature disposal in June, 40 ° of C6 month disposal etc.), adopt the present invention's described determination and determination of foreign matter method of method of testing part above, measure these samples before disposal (0 month), rear (June) active component with respect to the content of labelled amount, and before disposal the content of (0 month), rear (June) impurity A.
For each sample, with following formula, calculate its relative amount (%) during with respect to 0 month when the June, it also can be described as residual content in June (%) in the present invention:
Residual content (%)=(0 month content of content ÷ in June) * 100%
For each sample, with following formula, calculating its impurity A when the June increases percentage amounts (%):
Impurity A increase percentage amounts (%)=[(impurity A in June content-0 month impurity A content) 0 month impurity A content of ÷)] * 100%
Result:
(1) residual content (%):
For Ex1, B14, B15, B16, B17, B18, B19, B10, B24, B25, B26, B27, B28, B29, B20, these use the sorbitol of q.s and the tablet of Sucralose simultaneously, their residual content in June (%) is all in 98% ~ 101% scope, and for example the residual content in June (%) of Ex1 is 99.6%;
For B11, B12, B13, B21, B22, B23, B31, B32, B33, B34, B35, B36, B37, B38, B39, B41, B42, B43, B44, B45, B46, B47, B48, B49, B51, B52, B53, B61, B62, B63, B64, these do not use sorbitol and Sucralose or by quantity not sufficient or change the tablet of sorbitol-Sucralose blend step simultaneously, their residual content in June (%) is all in 86% ~ 92% scope, and for example the residual content in June (%) of B21 is 87.8%;
As everyone knows, the test of above-mentioned high-temperature treatment is the test of this area classics, is generally speaking acceptable during residual content (%) >90% during June, otherwise thinks that product can not meet the demands.From above result, the tablet with feature of the present invention has good stability, and for example residual content is still very high after June in high-temperature process, and does not adopt the present invention program's tablet present defective or approach underproof result.
(2) impurity A increases percentage amounts (%):
For Ex1, B14, B15, B16, B17, B18, B19, B10, B24, B25, B26, B27, B28, B29, B20, these use the sorbitol of q.s and the tablet of Sucralose simultaneously, when June, impurity A increase percentage amounts (%) is all within the scope of 44-69% for their, and for example the impurity A of Ex1 increase percentage amounts (%) is 48.1%;
For B11, B12, B13, B21, B22, B23, B31, B32, B33, B34, B35, B36, B37, B38, B39, B41, B42, B43, B44, B45, B46, B47, B48, B49, B51, B52, B53, B61, B62, B63, these are not used sorbitol and Sucralose or by quantity not sufficient or change the tablet of sorbitol-Sucralose blend step B64 simultaneously, their impurity As when June increase percentage amounts (%) all within the scope of 44-69%, for example the impurity A of Ex1 increase percentage amounts (%) is in 168% ~ 273% scope, for example the impurity A increase percentage amounts in June (%) of B11 is 207.2%.From above result, the tablet with feature of the present invention have good stability for example aspect the impurity A of the special monitoring of needs increase less, and the demonstration that does not adopt the present invention program's tablet to present impurity A increases.
test example 2: the character of investigating tablet of the present invention
(1) uniformity of dosage units:
Measure above-described embodiment 1 and supplementary example 1 to the uniformity of dosage units (because the relative quantity of famotidine in tablet is very little, conventionally need to monitor its uniformity of dosage units in the case) that supplements famotidine in the whole tablets of example 6 gained.
The whole tablets that prepare in result: embodiment 1, supplementary example 1, supplementary example 2, supplementary example 3, supplementary example 4, supplementary example 5, their A+1.80S value is all in 1.4 ~ 6.3 scopes; And the A+1.80S value of supplementing four tablet samples that example 6 prepares is all in 13.6 ~ 17.2 scopes, approach defective limit even unqualified.
(2) contact angle:
After measured, the whole tablets that prepare in embodiment 1, supplementary example 1, supplementary example 2, supplementary example 3, supplementary example 4, supplementary example 5, their contact angle is all in the scope of 43 ° ~ 84 °; And supplement four tablet samples that example 6 prepares contact angle all in the scope of 97 ° ~ 116 °.
embodiment 2: prepare famotidine calcium magnesium chewable tablet
Formula is with embodiment 1, method for making is only different in step (5), change respectively the time of mixing into 0 hour under relative humidity 85% humid air stream poker part respectively (relative humidity is less than under 50% condition and mixes 5 hours), 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 8 hours, 10 hours, 15 hours, 20 hours, obtain 10 samples and be designated as respectively Ex21, Ex22, Ex23, Ex24, Ex25, Ex26, Ex27, Ex28, Ex29, Ex20.
Measure contact angle and the uniformity of dosage units of these 10 tablet samples, result:
Ex26, Ex27, Ex28, Ex29, these five incorporation times of Ex20 are at their contact angle of more than 5 hours tablets all in the scope of 46 ° ~ 83 °, and the longer contact angle of incorporation time is less; But Ex21, Ex22, Ex23, Ex24, their contact angle of this five incorporation time less thaies of Ex25 tablet of 5 hours be all in the scope of 94 ° ~ 119 °, and incorporation time more short circuit feeler is larger;
The A+1.80S value of Ex26, Ex27, Ex28, Ex29, these five tablets of Ex20 is all in 1.7 ~ 6.1 scopes; And the A+1.80S value of Ex21, Ex22, Ex23, Ex24, these five tablet samples of Ex25 is all in 13.1 ~ 16.9 scopes, approaches defective limit even unqualified.
According to the method for test example 1, measure residual content (%) and the impurity A of these 10 tablet samples after high temperature disposal in June and increase percentage amounts (%), the whole sample of result residual content in June (%) is all in 97% ~ 100% scope, and the whole sample of result impurity A in June increases percentage amounts (%) all within the scope of 38-65%.
embodiment 3: prepare famotidine calcium magnesium chewable tablet
Prescription:
Famotidine 10mg,
Calcium carbonate 750mg,
Magnesium hydroxide 180mg,
Sucralose 3mg,
Sorbitol 70mg,
Lactose 50mg,
Starch 200mg,
Tartrazine aluminum lake 0.2mg,
Cane sugar powder 250mg,
Oleum menthae 8mg,
30 POVIDONE K 30 BP/USP-15 (12% solution) are appropriate,
Fructus Citri Limoniae essence 8mg,
Magnesium stearate 20mg.
Method for making: the method with reference to embodiment 1 is carried out.
embodiment 4: prepare famotidine calcium magnesium chewable tablet
Prescription:
Famotidine 10mg,
Calcium carbonate 850mg,
Magnesium hydroxide 150mg,
Sucralose 10mg,
Sorbitol 30mg,
Lactose 200mg,
Starch 50mg,
Tartrazine aluminum lake 0.75mg,
Cane sugar powder 450mg,
Oleum menthae 2mg,
30 POVIDONE K 30 BP/USP-60 (8% solution) are appropriate,
Fructus Citri Limoniae essence 3mg,
Magnesium stearate 40mg.
Method for making: the method with reference to embodiment 1 is carried out.
embodiment 5: prepare famotidine calcium magnesium chewable tablet
Prescription:
Famotidine 10mg,
Calcium carbonate 780mg,
Magnesium hydroxide 175mg,
Sucralose 10mg,
Sorbitol 30mg,
Lactose 75mg,
Starch 150mg,
Tartrazine aluminum lake 0.7mg,
Cane sugar powder 400mg,
Oleum menthae 2mg,
PVP K-30 (9% solution) is appropriate,
Fructus Citri Limoniae essence 4mg,
Magnesium stearate 40mg.
Method for making: the method with reference to embodiment 1 is carried out.
embodiment 6: prepare famotidine calcium magnesium chewable tablet
Prescription:
Famotidine 10mg,
Calcium carbonate 820mg,
Magnesium hydroxide 155mg,
Sucralose 3mg,
Sorbitol 70mg,
Lactose 150mg,
Starch 75mg,
Tartrazine aluminum lake 0.3mg,
Cane sugar powder 300mg,
Oleum menthae 6mg,
30 POVIDONE K 30 BP/USP-15 (11% solution) are appropriate,
Fructus Citri Limoniae essence 6mg,
Magnesium stearate 20mg.
Method for making: the method with reference to embodiment 1 is carried out.
test example 3: the character of investigating tablet of the present invention
Measure contact angle, the uniformity of dosage units of four tablet samples of embodiment 3 to embodiment 6 gained, result: the contact angle of four tablets is all in the scope of 57 ° ~ 78 °, and the A+1.80S value of four tablets is all in 2.2 ~ 5.4 scopes.
According to the method for test example 1, measure residual content (%) and the impurity A of these four tablet samples after high temperature disposal in June and increase percentage amounts (%), result: all sample residual content in June (%) is all in 98% ~ 100% scope, and the whole sample of result impurity A in June increases percentage amounts (%) all within the scope of 32-54%.
supplement example 7: prepare famotidine calcium magnesium chewable tablet
Formula is respectively 3 to embodiment 6 four formulas of above embodiment, and method for making is carried out with reference to the method for making of B51 tablet, obtains four tablet samples and is designated as respectively B701, B702, B703, B704 (famotidine mixing order modification).
Formula is respectively 3 to embodiment 6 four formulas of above embodiment, and method for making is carried out with reference to the method for making of B53 tablet, obtains four tablet samples and is designated as respectively B705, B706, B707, B708 (famotidine mixing order modification).
Formula is respectively 3 to embodiment 6 four formulas of above embodiment, and method for making is carried out with reference to the method for making of Ex21 tablet, obtains four tablet samples and is designated as respectively B709, B710, B711, B712 (change of calcium carbonate/magnesium hydroxide hybrid mode).
Formula is respectively 3 to embodiment 6 four formulas of above embodiment, and method for making is carried out with reference to the method for making of Ex23 tablet, obtains four tablet samples and is designated as respectively B713, B714, B715, B716 (change of calcium carbonate/magnesium hydroxide hybrid mode).
Contact angle, the uniformity of dosage units of measuring 12 tablet samples of these supplementary example 7 preparations, the contact angle of eight tablets of result: B701 ~ B708 is all in the scope of 57 ° ~ 78 °, and the A+1.80S value of eight tablets of B701 ~ B708 is all in 2.3 ~ 5.4 scopes; The contact angle of eight tablets of B709 ~ B716 is all in the scope of 95 ° ~ 108 °, and the A+1.80S value of eight tablets of B709 ~ B716 is all in 13.8 ~ 17.4 scopes.
Residual content (%) and the impurity A increase percentage amounts (%) of 12 tablet samples measuring these supplementary example 7 preparations according to the method for test example 1 after high temperature is disposed June, the residual content in June (%) of eight tablets of result: B701 ~ B708 is all in 88% ~ 92% scope, and the residual content in June (%) of eight tablets of B709 ~ B716 is all in 96% ~ 99% scope; The impurity A increase percentage amounts in June (%) of eight tablets of B701 ~ B708 is all within the scope of 173-204%, and the impurity A in June of eight tablets of B709 ~ B716 increases percentage amounts (%) all within the scope of 45-71%.
The above results demonstration, famotidine calcium magnesium chewable tablet of the present invention has good characteristic, and this good characteristic is the result of many factors fine adjustment.
By preferred embodiment of the present invention, spirit of the present invention is elaborated above.It will be appreciated by those skilled in the art that every any modification, equivalent variations and modification of above embodiment being done according to the technology of the present invention essence, all drop in protection scope of the present invention.
Claims (10)
1. famotidine calcium magnesium chewable tablet, wherein comprises famotidine, calcium carbonate, magnesium hydroxide.
2. the famotidine calcium magnesium chewable tablet of claim 1, is characterized in that following any one or multinomial:
(1) wherein comprise famotidine 10 weight portions, calcium carbonate 750 ~ 850 weight portions (for example 780 ~ 820 weight portions, for example 800 weight portions), magnesium hydroxide 150 ~ 180 weight portions (for example 155 ~ 175 weight portions, for example 165 weight portions);
(2) wherein also comprise sorbitol;
(3) for the famotidine of every 10 weight portions, wherein the amount of sorbitol is 10 ~ 100 weight portions, for example 20 ~ 80 weight portions, for example 30 ~ 70 weight portions;
(4) wherein also comprise Sucralose;
(5) for the famotidine of every 10 weight portions, wherein the amount of Sucralose is 1 ~ 20 weight portion, for example 2 ~ 15 weight portions, for example 3 ~ 10 weight portions;
(6) wherein said sorbitol and Sucralose are after fully mixing together with famotidine, to add in other material of this tablet again.
3. the famotidine calcium magnesium chewable tablet of claim 1 to 2, is characterized in that following any one or multinomial:
(1) wherein also comprise lactose;
(2) for the famotidine of every 10 weight portions, wherein the amount of lactose is 25 ~ 250 weight portions, for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions;
(3) wherein also comprise starch;
(4) for the famotidine of every 10 weight portions, wherein the amount of starch is 25 ~ 250 weight portions, for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions;
(5) wherein also comprise cane sugar powder;
(6) for the famotidine of every 10 weight portions, wherein the amount of cane sugar powder is 200 ~ 500 weight portions, for example 250 ~ 450 weight portions, for example 300 ~ 400 weight portions.
4. the famotidine calcium magnesium chewable tablet of claims 1 to 3, is characterized in that following any one or multinomial:
(1) wherein also comprising aluminum color forms sediment;
(2) described aluminum color lake can be Ponceau 4R aluminum lake;
(3) for the famotidine of every 10 weight portions, wherein the amount in aluminum color lake is 0.1 ~ 1 weight portion, for example 0.2 ~ 0.75 weight portion, for example 0.3 ~ 0.7 weight portion;
(4) wherein also comprise Oleum menthae;
(5) for the famotidine of every 10 weight portions, wherein the amount of Oleum menthae is 1 ~ 15 weight portion, for example 2 ~ 12 weight portions, for example 2 ~ 8 weight portions, for example 2 ~ 6 weight portions;
(6) wherein also comprise essence;
(7) described essence can be flavoring orange essence;
(8) for the famotidine of every 10 weight portions, wherein the amount of essence is 1 ~ 15 weight portion, for example 2 ~ 12 weight portions, for example 3 ~ 8 weight portions, for example 4 ~ 6 weight portions;
(9) wherein also comprise magnesium stearate;
(10), for the famotidine of every 10 weight portions, wherein the amount of magnesium stearate is 10 ~ 50 weight portions, for example 20 ~ 40 weight portions;
(11) wherein also comprise polyvidone;
(12) described polyvidone is PVP K-30,30 POVIDONE K 30 BP/USP-15 or 30 POVIDONE K 30 BP/USP-60;
(13) wherein said polyvidone is to add as the consumption of binding agent;
(14) wherein said polyvidone is that water is mixed with the consumption as binding agent after the solution of concentration 8 ~ 12% and adds.
5. the famotidine calcium magnesium chewable tablet of claim 1 to 4, it has the contact angle that is less than 110 °, and for example it has the contact angle that is less than 100 °, for example, have the contact angle that is less than 90 °, and for example the contact angle of 40 ~ 90 °, particularly has the contact angle of 40 ~ 85 °.
6. the famotidine calcium magnesium chewable tablet of claim 1 to 5, wherein said calcium carbonate, magnesium hydroxide are after mixing homogeneously with cane sugar powder three, under relative humidity 85% humid air stream poker part, mix after at least 5 hours again, then prepare with other mixing of materials that tablet uses and join in described tablet.
7. the famotidine calcium magnesium chewable tablet of claim 1 to 6, wherein comprises:
Famotidine 10 weight portions,
Calcium carbonate 750 ~ 850 weight portions (for example 780 ~ 820 weight portions, for example 800 weight portions),
Magnesium hydroxide 150 ~ 180 weight portions (for example 155 ~ 175 weight portions, for example 165 weight portions),
Sorbitol 10 ~ 100 weight portions (for example 20 ~ 80 weight portions, for example 30 ~ 70 weight portions),
Sucralose 1 ~ 20 weight portion (for example 2 ~ 15 weight portions, for example 3 ~ 10 weight portions),
Lactose 25 ~ 250 weight portions (for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions),
Starch 25 ~ 250 weight portions (for example 50 ~ 200 weight portions, for example 75 ~ 150 weight portions),
Cane sugar powder 200 ~ 500 weight portions (for example 250 ~ 450 weight portions, for example 300 ~ 400 weight portions),
Aluminum color lake 0.1 ~ 1 weight portion (for example 0.2 ~ 0.75 weight portion, for example 0.3 ~ 0.7 weight portion),
Oleum menthae 1 ~ 15 weight portion (for example 2 ~ 12 weight portions, for example 2 ~ 8 weight portions, for example 2 ~ 6 weight portions),
The amount of essence be 1 ~ 15 weight portion (for example 2 ~ 12 weight portions, for example 3 ~ 8 weight portions, for example 4 ~ 6 weight portions),
The amount of magnesium stearate is 10 ~ 50 weight portions, for example 20 ~ 40 weight portions and
Appropriate polyvidone.
8. the famotidine calcium magnesium chewable tablet of claim 1 to 7, is characterized in that:
It is under the condition of packing, be placed under 40 ° of C, lucifuge condition and place 6 months, this famotidine calcium magnesium chewable tablet residual content (%) during June of the relative amount (%) during with respect to 0 month when June is greater than 95%, for example, be 95% ~ 102%, for example, be 96% ~ 101%; And/or
It is placed under 40 ° of C, lucifuge condition and places 6 months under the condition of packing, and this famotidine calcium magnesium chewable tablet impurity A when June increases percentage amounts (%) and is less than 75%, for example, be 20 ~ 100%, for example, be 30 ~ 80%, for example, be 30 ~ 75%.
9. the method for preparing the famotidine calcium magnesium chewable tablet of claim 1-8 any one, it comprises the following steps:
(1) povidone solution that compound concentration is 8 ~ 12%, standby;
(2) each solid material is pulverized respectively, crossed 120 mesh sieves;
(3) get Oleum menthae, the starch mix homogeneously of recipe quantity, place one day, standby;
(4) famotidine, Sucralose, sorbitol three of getting recipe quantity be mix homogeneously fully, standby;
(5) cane sugar powder, calcium carbonate, magnesium hydroxide of getting recipe quantity be mix homogeneously fully, then mixes at least 5 hours under relative humidity 85% humid air stream poker part, standby;
(6) get aluminum color lake and the lactose mix homogeneously of recipe quantity, standby;
(7) by above step (4) ~ (6) gained material mix homogeneously, by step (1) gained povidone solution, be binding agent, wet granulation, transfers to gained wet granular in air dry oven 60 ~ 80
odry 2 ~ 4 hours of C, granulate, obtains dry granule;
(8) by step (3) gained mixture and the dry granule of step (7) gained and the magnesium stearate of recipe quantity, the essence of recipe quantity is mixed homogeneously, obtain eventually mixed granule;
(9), by the every specification containing famotidine 10mg, by the eventually mixed granule tabletting on tablet agent of step (8) gained, obtain famotidine calcium magnesium chewable tablet.
10. the method for claim 9, the method is preparation-obtained does not have for fourth calcium magnesium chewable tablet the contact angle that is less than 110 °, and for example it has the contact angle that is less than 100 °, for example, have the contact angle that is less than 90 °, for example the contact angle of 40 ~ 90 °, particularly has the contact angle of 40 ~ 85 °.
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| CN201410377785.4A CN104095875B (en) | 2014-08-04 | 2014-08-04 | Famotidine calcium and magnesium chewable tablet |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104971073A (en) * | 2015-05-29 | 2015-10-14 | 西南药业股份有限公司 | Famotidine calcium carbonate and magnesium hydroxide chewable tablet preparation method and product thereof |
| CN113143875A (en) * | 2020-12-30 | 2021-07-23 | 河南合智医药科技有限公司 | Taste-masking compound famotidine chewable tablet and preparation method thereof |
| CN114340599A (en) * | 2019-09-27 | 2022-04-12 | 强生消费者公司 | Gel chewable dosage form |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1768744A (en) * | 2005-10-14 | 2006-05-10 | 四川泰华堂制药有限公司 | Method for preparing compound famotidine chewing tablet |
| WO2009095210A1 (en) * | 2008-01-31 | 2009-08-06 | Bayer Consumer Care Ag | Composition comprising an antacid and a h2-antagonists |
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2014
- 2014-08-04 CN CN201410377785.4A patent/CN104095875B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1768744A (en) * | 2005-10-14 | 2006-05-10 | 四川泰华堂制药有限公司 | Method for preparing compound famotidine chewing tablet |
| WO2009095210A1 (en) * | 2008-01-31 | 2009-08-06 | Bayer Consumer Care Ag | Composition comprising an antacid and a h2-antagonists |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104971073A (en) * | 2015-05-29 | 2015-10-14 | 西南药业股份有限公司 | Famotidine calcium carbonate and magnesium hydroxide chewable tablet preparation method and product thereof |
| CN104971073B (en) * | 2015-05-29 | 2018-01-12 | 西南药业股份有限公司 | Preparation method of famotidine calcium and magnesium chewable tablets and products thereof |
| CN114340599A (en) * | 2019-09-27 | 2022-04-12 | 强生消费者公司 | Gel chewable dosage form |
| CN113143875A (en) * | 2020-12-30 | 2021-07-23 | 河南合智医药科技有限公司 | Taste-masking compound famotidine chewable tablet and preparation method thereof |
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| CN104095875B (en) | 2016-06-29 |
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