CN101756918A - Orally disintegrating tablet containing paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide and preparation method thereof - Google Patents
Orally disintegrating tablet containing paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide and preparation method thereof Download PDFInfo
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- CN101756918A CN101756918A CN200810233324A CN200810233324A CN101756918A CN 101756918 A CN101756918 A CN 101756918A CN 200810233324 A CN200810233324 A CN 200810233324A CN 200810233324 A CN200810233324 A CN 200810233324A CN 101756918 A CN101756918 A CN 101756918A
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Abstract
The invention relates to a compound orally disintegrating tablet containing paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide and a preparation method thereof. The preparation method is characterized by comprising the following steps of: uniformly mixing and dissolving the three kinds of active substances, uniformly mixing the three kinds of active components by adopting a spray drying technology of a fluidized bed to process so that mixed powder is obtained, and then pelletizing, coating and tabletting so that the orally disintegrating tablet is obtained. The orally disintegrating tablet has the advantages of simple process and uniform quality.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to compound oral disintegrating tablet of a kind of acetaminophen, pseudoephedrine hydrochloride and dextromethorphan hydrobromide and preparation method thereof.
Technical background
Flu is a kind of common frequently-occurring disease, it is generally acknowledged that common cold is caused by rhinovirus, owing to still do not have specific drug for virus at present, so the main symptomatic treatment that adopts.The eighties initial stage, various countries all were devoted to develop the catch a cold medicine of all symptoms of comprehensive covering.Through the development of more than ten years, be used for preventing that the compound preparation that cures cold is wide in variety, the medicine name is many, dosage form is many, and is innumerable now on the market in the pharmacy.Though anti-cold compound formulation kind is many, from contained main component, medicine commonly used is mainly antiallergic agent, alleviates nasal mucosa congestion and edema medicine, antipyretic analgesic three major types.Antiallergic agent is often selected chlorphenamine (chlorphenamine).The medicine that alleviates nasal mucosa hyperemia often selects pseudoephedrine.Be mainly the mucositis symptom of slowing down flu with this medicine of two types.Pseudoephedrine can alleviate nasal obstruction, watery nasal discharge and not have cardiac stimulus to cause cardiopalmus and shrink the untoward reaction that peripheral blood vessel causes elevation of the blood pressure, and chlorphenamine and pseudoephedrine have synergism to alleviating the mucositis symptom.Antipyretic analgesic is often selected acetaminophen, aspirin for use.Because one of cardinal symptom of flu is to have a headache, generate heat, select for use this class medicine with symptomatic treatment.Also have cough medicine and antiviral agents in the composition of compound recipe coldrex.Cough medicine is often selected the central antitussive dextromethorphan for use, and it has antitussive effect preferably.The most prescriptions of antiviral agents are selected amantadine for use, and it has certain effect to influenza A virus, but due to illness poison variation, its curative effect does not affirm that amantadine also has certain side effect simultaneously.So ordinary circumstance without this medicine for well.
The child since the immunity of health a little less than, at the change of season, very easily catch a cold, if untimely treatment, can concurrent bronchitis, pneumonia and even concurrent otitis media, myocarditis etc.In the children's who catches a cold, particularly premature infant, low birthweight infant or congenital heart disease, malnutrition, anemia, child suffering from rickets are arranged because weak, in case pneumonia, often state of an illness threat to life or protracted course of disease.Therefore, need carry out Drug therapy timely.For this special medication colony of child, be very important for it provides suitable specification and dosage form, yet opposite with its market demand be, specialize in flu medication that the child uses and few at present on the market.
At present, the exploitation listing of children's cold medicine salable on the market---Anfenmame syrup (little white sugar syrup) reason Topsun Science And Technology Qidong Gaitianli Pharmaceutical Co., Ltd, its packing specification is every bottle of 100ml, include: acetaminophen 1600mg, pseudoephedrine hydrochloride 150mg, dextromethorphan hydrobromide 50mg.This syrup system is a children's development specially, acetaminophen in the prescription has pain relieving and antipyretic effect, be the long-term clinical verification of a kind of process, be extensive use of antipyretic analgesic safely and effectively both at home and abroad, it produces refrigeration function by the hypothalamus thermotaxic centre.Be used for the treatment of chronic pain, puerperal and postoperative pain, the heating of headache, myalgia, arthralgia, cancer patient.Pseudoephedrine hydrochloride is a decongestant drug, the effect of alleviating nasopharynx part mucous hyperemia, swelling is arranged, can make the nasal obstruction sx, oral back is main by stimulating SNE to discharge norepinephrine, play sympatheticomimetic action with indirect mode, its vasoconstrictive effect has selectivity, mainly shrinks the upper respiratory tract blood vessel, less to the influence of whole body blood vessel, little to the blood pressure influence.Dextromethorphan hydrobromide is a cough medicine, and WHO in 1988 recommend to replace the highly effective and safe antitussive of codeine, has no drug resistance and addiction, is fit to long-term Drug therapy and children taking.Three hospitals such as BJ Union Hospital have carried out the clinical efficacy checking in May, 95 to little white sugar syrup
[7]The result shows little white sugar syrup treatment children's cold total effective rate 92.2%, wherein obvious effective rate 81.9%, body temperature is reduced to normally after on average taking medicine 1.85 days, can control or improve cold symptoms effectively after taking medicine 3 days, be better than matched group in aspect curative effects such as eliminating heating, headache, general pain, pharyngalgia, cough especially.
Therefore little white sugar syrup is that a prescription is reasonable, the children's cold medicine that curative effect is sure.Syrup is the conventional dosage forms of children, be easy to swallow and advantage such as divided dose, but also easily broken just like packing, carry inconvenience, contain sugar and too much cause dental caries and obesity, and dosage is difficult for dividing shortcomings such as accurate, particularly under main bitter situation, child's resisting psychology is stronger.Because oral cavity disintegration tablet has mouthfeel good, taste is fragrant and sweet, and dosage is accurate, and therefore advantage such as be easy to carry, will bring a new selection for the clinical application of children's cold with little white sugar syrup exploitation oral cavity disintegration tablet.CN1771915 discloses and has contained acetaminophen 1600mg, the Anfenmame oral cavity disintegration tablet of pseudoephedrine hydrochloride 150mg and dextromethorphan hydrobromide 50mg, its preparation is main adopts wet grain comminution granulation to make granule coating then, obtain coated granule, add the adjuvant tabletting again, its being attacked by dampness grain pelletize be with three kinds of active ingredients respectively granulation, coating, mix, add the adjuvant tabletting, perhaps with the dry powder blend of three kinds of active ingredients, add binder solution and make granule, again the coating tabletting.Last person's method; the oral cavity disintegration tablet of preparation is uneven because of three kinds of coated granules mix; it is off quality poor with homogeneity to cause, and influences product quality and therapeutic effect, simultaneously; because of three kinds of active substances difference coatings; complex manufacturing, man-hour is long, cost is high, is unfavorable for suitability for industrialized production, and the latter adopts to do and mixes; can bring equally and mix uneven problem, influence product quality and curative effect.For solving above existing problems, the inventor adopts the solution that three kinds of active substances is made into mix homogeneously, adopt the bed spray dry technology to handle again, three kinds of active component are obtained mixed-powder, granulation again, coating, tabletting, the according to said method uniform in quality of Huo Deing with the mixing of molecular dispersion state equably, the taste masking characteristics have been kept, solved the technological deficiency of depositing at present, now, simple, the suitable suitability for industrialized production of this method technological operation.
Summary of the invention
Purpose of the present invention provides a kind of Anfenmame compound oral disintegrating tablet, comprise the compositions that a) comprises acetaminophen, dextromethorphan hydrobromide and the pseudoephedrine hydrochloride of imitating dosage, b) coating material, and c) is suitable for the pharmaceutic adjuvant of disintegrating agent, it is characterized in that: said compositions is to be dissolved at 32: 2: 1 in ethanol and/or the water by its weight ratio by acetaminophen, dextromethorphan hydrobromide and pseudoephedrine hydrochloride, mixes homogeneous, spray drying and getting.
Compound oral disintegrating tablet of the present invention, so-called " effective dose " can be understood as effective pharmaceutical dosage for medicine.Active drug dosage is to be enough to cause the medicine that required treatment is replied or the dosage of active medicinal matter, in other words, when to patient's administration, this dosage is enough to cause tangible biological response, preferred acetaminophen 80mg, pseudoephedrine hydrochloride 7.5mg, dextromethorphan hydrobromide 2.5mg.
Compound oral disintegrating tablet of the present invention, said coating material acrylic resin, hydroxypropyl methylcellulose, ethyl cellulose, its consumption are 5%～50% of medicinal active ingredient consumption.
Compound oral disintegrating tablet of the present invention, said pharmaceutic adjuvant comprises disintegrating agent, filler, lubricant, fluidizer, sweeting agent or essence, wherein, disintegrating agent is cross-linking sodium carboxymethyl cellulose (crosslinked CMC-Na, Ac-Di-Sol), crospolyvinylpyrrolidone (PVPP) or crosslinked carboxymethyl fecula sodium (crosslinked CMS-Na), its amount ranges be sheet heavy 1～10%; Filler is mannitol or microcrystalline Cellulose, preferred mannitol and mannitol 200SD, and wherein mannitol 200SD is the direct compression type mannitol that Roquette Freres produces.When using mannitol 200SD separately, can improve the flowability of powder body, but disintegrate is out of condition; And when using mannitol separately, can improve the disintegrate situation, but flowability is not good.If two kinds of mannitol are proportionally mixed use, then can when improving liquidity, improve the disintegrate situation; Lubricant is that Pulvis Talci, magnesium stearate, its consumption are 0.1～2%, fluidizer is micropowder silica gel, hard ester fumaric acid sodium, and its consumption is 0.1～2%.
Compound oral disintegrating tablet of the present invention in case of necessity, also can contain other adjuvants, comprising: essence, diluent, coloring agent, binding agent, filler, fine and close excipient and non-gas-producing disintegrant.
Available binding agent comprises: hydroxypropyl methylcellulose, arabic gum, tragakanta, gelatin, starch fiber cellulosic material (for example: hydroxypropyl methylcellulose, methylcellulose and sodium carboxymethyl cellulose, alginic acid and salt thereof), aluminium-magnesium silicate, Polyethylene Glycol, guar gum, polysaccharide acid, Bentonite, sugar, Nulomoline etc., adhesive consumption can be up to 60% (w/w), 10% to 40% of optimizing prescriptions gross weight, preferred hydroxypropyl methylcellulose.
Non-gas-producing disintegrant comprises: starch (as: corn starch, potato starch and modified starch thereof), sweeting agent, clay (as Bentonite), microcrystalline Cellulose, alginate, colloid (as agar), sugar, locust bean gum, karaya, colloid and tragakanta.Disintegrating agent can account for 20%, preferred 2% to 10% of prescription gross weight.
Coloring agent comprises: titanium dioxide, be applicable to the dyestuff (F.D.﹠amp as is known of food; The C dyestuff), reach natural colorant (as Pericarpium Vitis viniferae extract, beet red powder, beta-carotene, roucou, carmine, Rhizoma Curcumae Longae, Fructus Capsici powder etc.).The amount ranges of coloring agent is 0.1% to 3.5% of a prescription gross weight.
The spice that is added in the prescription can be selected from the perfumery oil of synthetic, seasoning aromatic and/or natural oil, the extract of plant, leaves, flower, fruit etc., or its mixture.Comprising Oleum Cinnamomi, wintergreen oil, Oleum menthae, Oleum Caryophylli, laurel fat, Oleum Anisi Stellati, Eucalyptus oil, Oleum thymi vulgaris, Cedar leaf oil, Semen Myristicae oil, sage oil, oil of bitter almond and Oleum Cinnamomi.Can also having: vanilla, citrus Oleum sesami (comprising: Fructus Citri Limoniae, orange, Citrus aurantium Linn. and grapefruit), and fruit essence (comprising: Fructus Mali pumilae, pears, peach, Fructus Fragariae Ananssae, raspberry, Fructus Pruni pseudocerasi, prunus mume (sieb.) sieb.et zucc., Fructus Ananadis comosi, Fructus Pruni etc.) as spice.Commercially available conventional perfumes comprises orange essence, grape essence, cherry essence, bubble gum flavor and composition thereof, and first-selected essence is Fructus Vitis viniferae and cherry essence, and the consumption of citrus spices and essence depends on multiple factor, comprising the demand of sensory effects.The consumption of essence can account for 0.5% to 3.0% of prescription gross weight.
Compound oral disintegrating tablet of the present invention, said spray drying is meant the employing fluidization, the top spray is dry; Further comprise to dry and compositions pulverize in case of necessity and obtain fine powder, granulate again, said granulation is to adopt fluidization, side spray grain.
Compound oral disintegrating tablet of the present invention, said coating are to adopt fluidization, end spray coating, and the coated granule that obtains also can wrap by one deck hydrophilic material again, has the effect of removing static and preventing the coated granule adhesion.
Compound oral disintegrating tablet of the present invention, the mixed solution of three kinds of active substances can add a spot of Pulvis Talci before by spray drying, also can place a spot of Pulvis Talci in coating solution, also can add an amount of Pulvis Talci in binder solution.
Another object of the present invention provides a kind of preparation method of compound oral disintegrating tablet of claim 1, and its process comprises:
A) the preparation mixed-powder takes by weighing acetaminophen, dextromethorphan hydrobromide and pseudoephedrine hydrochloride and is dissolved in ethanol or the water, mix homogeneously, and after the spray drying, mechanical activation comminution is crossed 100 sieves in case of necessity, makes mixed-powder;
B) granulation, the powder adding suitable amount of adhesive solution with gained of last step adopts fluidized bed granulation, crosses 80 sieves, gets granule;
C) coating adopts the spray coating mode to the granule coating that the last step makes with the alcoholic solution that contains coating material, obtains coated granule;
D) then with coated granule with after the pharmaceutic adjuvant adjuvant of suitable disintegrating agent mixes, direct compression.
The method that the present invention is above-mentioned on the coated granule of making, also can be wrapped by one deck hydrophilic material, and said hydrophilic material is mannitol or sucrose.
The method that the present invention is above-mentioned, said spray drying adopts fluidization, and the top spray is dry; Fluidization, side spray grain are adopted in said granulation.
The method that the present invention is above-mentioned also further is included in step a), b), c) in add a spot of Pulvis Talci.
The method that the present invention is above-mentioned, acetaminophen, dextromethorphan hydrobromide and pseudoephedrine hydrochloride, its weight ratio is 32: 2: 1, its consumption is an effective dose, preferred acetaminophen 80mg, pseudoephedrine hydrochloride 7.5mg, dextromethorphan hydrobromide 2.5mg.
The method that the present invention is above-mentioned, said coating material are acrylic resin, hydroxypropyl methylcellulose, ethyl cellulose, or their any mixture, and its consumption is 5%～50% of a medicinal active ingredient consumption; The pharmaceutic adjuvant of said suitable disintegrating agent comprises disintegrating agent, filler, lubricant, fluidizer, binding agent, sweeting agent or essence,
Wherein, disintegrating agent is cross-linking sodium carboxymethyl cellulose (crosslinked CMC-Na, Ac-Di-Sol), crospolyvinylpyrrolidone (PVPP) or crosslinked carboxymethyl fecula sodium (crosslinked CMS-Na), its amount ranges be sheet heavy 1～10%;
Filler is mannitol or microcrystalline Cellulose, preferred mannitol and mannitol 200SD, and wherein mannitol 200SD is the direct compression type mannitol that Roquette Freres produces.When using mannitol 200SD separately, can improve the flowability of powder body, but disintegrate is out of condition; And when using mannitol separately, can improve the disintegrate situation, but flowability is not good.If two kinds of mannitol are proportionally mixed use, then can when improving liquidity, improve the disintegrate situation;
Fluidizer and lubricant are selected common micropowder silica gel, Pulvis Talci, magnesium stearate etc. for use;
Sweeting agent is sweeting agent commonly used,, sucrose sweet as A Basi, stevioside etc.;
Available binding agent comprises: hydroxypropyl methylcellulose, arabic gum, tragakanta, gelatin, starch fiber cellulosic material (for example: methylcellulose and sodium carboxymethyl cellulose, alginic acid and salt thereof), aluminium-magnesium silicate, Polyethylene Glycol, guar gum, polysaccharide acid, Bentonite, sugar, Nulomoline etc.Adhesive consumption can be up to 60% (w/w), 10% to 40% of optimizing prescriptions gross weight.
Essence can be selected from the perfumery oil of synthetic, seasoning aromatic and/or natural oil, the extract of plant, leaves, flower, fruit etc., or its mixture.Comprising Oleum Cinnamomi, wintergreen oil, Oleum menthae, Oleum Caryophylli, laurel fat, Oleum Anisi Stellati, Eucalyptus oil, Oleum thymi vulgaris, Cedar leaf oil, Semen Myristicae oil, sage oil, oil of bitter almond and Oleum Cinnamomi.Can also having: vanilla, citrus Oleum sesami (comprising: Fructus Citri Limoniae, orange, Citrus aurantium Linn. and grapefruit), and fruit essence (comprising: Fructus Mali pumilae, pears, peach, Fructus Fragariae Ananssae, raspberry, Fructus Pruni pseudocerasi, prunus mume (sieb.) sieb.et zucc., Fructus Ananadis comosi, Fructus Pruni etc.) as spice.Commercially available conventional perfumes comprises orange essence, grape essence, cherry essence, bubble gum flavor and composition thereof.The consumption of essence depends on multiple factor, comprising the demand of sensory effects.The consumption of essence can account for 0.5% to 3.0% of prescription gross weight.First-selected essence is Fructus Vitis viniferae and cherry essence, and citrus spice
Also can contain other adjuvants in the dosage form of the present invention, these adjuvants all are selected from known kind, comprising: diluent (water and ethanol etc.), non-gas-producing disintegrant and coloring agent.
Non-gas-producing disintegrant comprises: starch (as: corn starch, potato starch and modified starch thereof), sweeting agent, clay (as Bentonite), microcrystalline Cellulose, alginate, colloid (as agar), sugar, locust bean gum, karaya, colloid and tragakanta.Disintegrating agent can account for 20%, preferred 2% to 10% of prescription gross weight.
Coloring agent comprises: titanium dioxide, be applicable to the dyestuff (F.D.﹠amp as is known of food; The C dyestuff), reach natural colorant (as Pericarpium Vitis viniferae extract, beet red powder, beta-carotene, roucou, carmine, Rhizoma Curcumae Longae, Fructus Capsici powder etc.).The amount ranges of coloring agent is 0.1% to 3.5% of a prescription gross weight.
The specifically scheme realization as described below of preparation method that Anfenmame compound oral disintegrating tablet of the present invention is concrete:
The preparation process of oral disintegrated Anfenmame tablet is divided into two big steps: 1, the preparation of coating taste masked particle; 2, the compacting of tablet.
1, the preparation of coating taste masked particle:
A, take by weighing acetaminophen, pseudoephedrine hydrochloride and dextromethorphan hydrobromide, be added in the ethanol, heating for dissolving is made solution, adds Pulvis Talci again, stirs.Adopt fluidization, the top spray is dry, crosses 100 sieves after the discharging, makes the medicament mixed powder, and is standby;
B, claim binding agent to add in the entry as getting hydroxypropyl methylcellulose, stirring and dissolving, make solution after, add Pulvis Talci again, stir, make binder solution.The said medicine mixed-powder is added in the fluidising chamber, adopts fluidization, side spray grain is crossed 80 sieves after the discharging, standby;
C, take by weighing coating material such as acrylic resin and/or hydroxypropyl methylcellulose and/or ethyl cellulose, be added in the ethanol/water mixed solvent, stirring and dissolving is made solution, adds Pulvis Talci again, stirs, and makes the taste masking coating solution.Granule with the above-mentioned steps preparation is added in the fluidising chamber, adopts fluidization, and spray coating in the end is crossed 60 sieves after the discharging, standby;
D, take by weighing water solublity coating material such as mannitol or sucrose, be added in the water heating for dissolving.The coated granule of above-mentioned steps preparation is added in the fluidising chamber, adopts fluidization, spray coating in the end is crossed 60 sieves after the discharging, standby;
2, the compacting of tablet:
Mannitol is crossed 80 orders, take by weighing coated granule,, behind the mix homogeneously, adopt direct compression technology tabletting less than 80 purpose filleies, disintegrating agent, fluidizer, lubricant, sweeting agent and essence etc.
With reference to the disintegrate detection method of describing among the Chinese patent CN1271997, the disintegration of testing oral cavity disintegration tablet of the present invention, method is as follows:
Disintegration experimental provision: form by Chinese Pharmacopoeia version appendix in 2005 disintegration time mensuration plant modification.
The both ends open glass-tube that to get 6 diameters be 1.5cm, 25 order stainless steel meshs (mesh size is about 710 μ m) are overlapped in the bottom, and the overcoat transparent casing places water bath with thermostatic control with device, and bath temperature is 37 ± 1 ℃, adds 12ml water (every pipe＜2ml), constant temperature.
Inspection method: get 6 of this product, add respectively in each glass-tube, the disintegrate situation is observed in timing.All should in 1 minute, collapse diffusingly, not have accumulative block.
The glass-tube under item disintegration is got in the granularity inspection, checks immediately, if in the screen cloth residue is arranged, every pipe drips no more than 4ml water flushing residue, should be able to be all through screen cloth.Defective if any a slice, should get 12 and recheck, all should be up to specification.
Specific embodiment
Embodiment 1
The oral disintegrated Anfenmame tablet prescription:
Acetaminophen principal agent 80.0g
Pseudoephedrine hydrochloride principal agent 7.5g
Dextromethorphan hydrobromide is (with anhydride principal agent 2.5g
Meter)
Polyacrylic resin IV taste masking coating material 24g
Pulvis Talci antiplastering aid 19.5g
Hypromellose (0.03Pas) binding agent 4g
Mannitol filler 214.5g
Mannitol 200SD filler 100g
Polyvinylpolypyrrolidone disintegrating agent 30.0g
Milk flavour correctives 15.0g
Aspartame correctives 10.0g
Magnesium 5.0g
Micropowder silica gel fluidizer 2.5g
Amount to (sheet) 1000 (the heavy 500mg of sheet)
1, principal agent powder coating taste masking technology
1) takes by weighing after three kinds of principal agents of recipe quantity and Pulvis Talci be added in the ethanol dissolving or suspendible, adopt fluid bed top spray spray drying (adding an amount of Pulvis Talci in the fluid bed),, cross 100 mesh sieves dry thing mechanical activation comminution;
3) fine powder that makes being mixed with Pulvis Talci, is binding agent (including an amount of Pulvis Talci) with the HPMC water-alcohol solution, and round as a ball granulation in side spray fluid bed makes granule and crosses 80 mesh sieves;
4) granule after will sieving is with after Pulvis Talci mixes, be added in the end spray fluid bed, with polyacrylic resin IV alcoholic solution (including an amount of Pulvis Talci) coating, setting inlet temperature is 30 ℃, require medicine is carried out coating according to the equipment operation, increase weight about 20% until coating;
6) stop into coating solution, open drying, baking temperature is 30 ℃-40 ℃, dry 30min;
7) spray fluidized bed coating at the bottom of the reuse mannitol solution;
8) discharging is with 60 mesh sieve granulate;
9) analytical control drug coating granule is standby.
2, oral cavity disintegration tablet preparation technology
1) with crossing 80 mesh sieves after the mannitol mechanical activation comminution, standby;
2) drug coating granule, mannitol (having crossed 80 mesh sieves), mannitol 200SD and the polyvinylpolypyrrolidone that takes by weighing recipe quantity respectively crossed 60 mesh sieve mix homogeneously and made mixture 1, and be standby;
3) aspartame, magnesium stearate and the micropowder silica gel that takes by weighing recipe quantity respectively crossed 80 mesh sieve mix homogeneously and made mixture 2, and be standby;
4) with mixture 1 and mixture 2 mix homogeneously;
5) detect the semi-finished product content and the uniformity;
6) tabletting, the about 3kg of control slice, thin piece hardness;
7) check average sheet weight, hardness, outward appearance, disintegration;
8) packing;
Embodiment 2
The oral disintegrated Anfenmame tablet prescription:
Acetaminophen principal agent 80.0g
Pseudoephedrine hydrochloride principal agent 7.5g
Dextromethorphan hydrobromide (in anhydride) principal agent 2.5g
Hydroxypropyl methylcellulose taste masking coating material 4g
Ethyl cellulose antiplastering aid 20g
Pulvis Talci binding agent, porogen 19.5g
Hypromellose (0.03Pas) filler 4g
Mannitol filler 214.5g
Mannitol 200SD disintegrating agent 100g
Polyvinylpolypyrrolidone correctives 30.0g
Milk flavour correctives 15.0g
Aspartame lubricant 10.0g
Magnesium stearate fluidizer 5.0g
Micropowder silica gel principal agent 2.5g
Amount to 1000 of (sheet) principal agents (the heavy 500mg of sheet)
1, principal agent powder coating taste masking technology
1) takes by weighing after three kinds of principal agents of recipe quantity and Pulvis Talci be added in the ethanol dissolving or suspendible, adopt fluid bed top spray spray drying (adding an amount of Pulvis Talci in the fluid bed),, cross 100 mesh sieves dry thing mechanical activation comminution;
3) fine powder that makes being mixed with Pulvis Talci, is binding agent (including an amount of Pulvis Talci) with the HPMC water-alcohol solution, and round as a ball granulation in side spray fluid bed makes granule and crosses 80 mesh sieves;
4) granule after will sieving is with after Pulvis Talci mixes, be added in the end spray fluid bed, with alcoholic solution (the including an amount of Pulvis Talci) coating of ethyl cellulose and hypromellose, setting inlet temperature is 30 ℃, require medicine is carried out coating according to the equipment operation, increase weight about 20% until coating;
6) stop into coating solution, open drying, baking temperature is 30 ℃-40 ℃, dry 30min;
7) spray fluidized bed coating at the bottom of the reuse mannitol solution;
8) discharging is with 60 mesh sieve granulate;
9) analytical control drug coating granule is standby.
2, oral cavity disintegration tablet preparation technology
1) with crossing 80 mesh sieves after the mannitol mechanical activation comminution, standby;
2) drug coating granule, mannitol (having crossed 80 mesh sieves), mannitol 200SD and the polyvinylpolypyrrolidone that takes by weighing recipe quantity respectively crossed 60 mesh sieve mix homogeneously and made mixture 1, and be standby;
3) aspartame, magnesium stearate and the micropowder silica gel that takes by weighing recipe quantity respectively crossed 80 mesh sieve mix homogeneously and made mixture 2, and be standby;
4) with mixture 1 and mixture 2 mix homogeneously;
5) detect the semi-finished product content and the uniformity;
6) tabletting, the about 3kg of control slice, thin piece hardness;
7) check average sheet weight, hardness, outward appearance, disintegration;
8) packing.
Claims (11)
1. Anfenmame compound oral disintegrating tablet, the compositions that comprises the acetaminophen, dextromethorphan hydrobromide and the pseudoephedrine hydrochloride that a) comprise effective dose, b) coating material, c) be suitable for the pharmaceutic adjuvant of disintegrate, it is characterized in that: said compositions is to be dissolved in ethanol and/or water at 32: 2: 1 by acetaminophen, dextromethorphan hydrobromide and pseudoephedrine hydrochloride by weight, mix homogeneous, spray drying and getting.
2. the described compound oral disintegrating tablet of claim 1, acetaminophen 80mg, pseudoephedrine hydrochloride 7.5mg, dextromethorphan hydrobromide 2.5mg.
3. the described compound oral disintegrating tablet of claim 1, said coating material acrylic resin, hydroxypropyl methylcellulose, ethyl cellulose, its consumption are 5%～50% of medicinal active ingredient consumption.
4. the described compound oral disintegrating tablet of claim 1, said pharmaceutic adjuvant comprises disintegrating agent, filler, lubricant, fluidizer, sweeting agent or essence.
5. the described compound oral disintegrating tablet of claim 4, disintegrating agent is cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone or crosslinked carboxymethyl fecula sodium, its amount ranges be sheet heavy 1～10%; Described filler is mannitol or microcrystalline Cellulose; Described lubricant is that Pulvis Talci, magnesium stearate, its consumption are 0.1～2%, described fluidizer is micropowder silica gel, hard ester fumaric acid sodium, and its consumption is 0.1～2%.
6. the described compound oral disintegrating tablet of claim 1 is characterized in that: spray drying employing fluidization, top spray drying.
7. the preparation method of the compound oral disintegrating tablet of a claim 1, its process comprises:
A) the preparation mixed-powder takes by weighing acetaminophen, dextromethorphan hydrobromide and pseudoephedrine hydrochloride and is dissolved in ethanol or the water, mix homogeneously, and after the spray drying, mechanical activation comminution is crossed 100 sieves in case of necessity, makes mixed-powder;
B) granulation, the powder adding suitable amount of adhesive solution with gained of last step adopts fluidized bed granulation, crosses 80 sieves, gets granule;
C) coating adopts the spray coating mode to the granule coating that the last step makes with the alcoholic solution that contains coating material, obtains coated granule;
D) then with coated granule with after the pharmaceutic adjuvant adjuvant that is suitable for disintegrate mixes, direct compression.
8. method according to claim 7 on the coated granule of making, also can be wrapped by one deck hydrophilic material.
9. method according to claim 8, said hydrophilic material are mannitol or sucrose.
10. method according to claim 7, said spray drying adopts fluidization, and the top spray is dry; Fluidization, side spray grain are adopted in said granulation.
11. method according to claim 7 also further is included in step a), b), c) in add a spot of Pulvis Talci.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810233324A CN101756918A (en) | 2008-12-12 | 2008-12-12 | Orally disintegrating tablet containing paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810233324A CN101756918A (en) | 2008-12-12 | 2008-12-12 | Orally disintegrating tablet containing paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN101756918A true CN101756918A (en) | 2010-06-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810233324A Pending CN101756918A (en) | 2008-12-12 | 2008-12-12 | Orally disintegrating tablet containing paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide and preparation method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN101756918A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103169705A (en) * | 2011-12-23 | 2013-06-26 | 重庆医药工业研究院有限责任公司 | Compound orally disintegrating tablet containing chlorpheniramine and dextromethorphan |
| CN103169706A (en) * | 2011-12-26 | 2013-06-26 | 重庆医药工业研究院有限责任公司 | Compound oral disintegrating tablet containing acetaminophen and dextromethorphan |
-
2008
- 2008-12-12 CN CN200810233324A patent/CN101756918A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103169705A (en) * | 2011-12-23 | 2013-06-26 | 重庆医药工业研究院有限责任公司 | Compound orally disintegrating tablet containing chlorpheniramine and dextromethorphan |
| CN103169706A (en) * | 2011-12-26 | 2013-06-26 | 重庆医药工业研究院有限责任公司 | Compound oral disintegrating tablet containing acetaminophen and dextromethorphan |
| CN103169706B (en) * | 2011-12-26 | 2016-08-03 | 重庆医药工业研究院有限责任公司 | A kind of compound oral disintegrating tablet containing acetaminophen and dextromethorphan |
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Application publication date: 20100630 |