CN1679525A - Oral disintegrant of compound paracetamol - Google Patents
Oral disintegrant of compound paracetamol Download PDFInfo
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- CN1679525A CN1679525A CN 200510023272 CN200510023272A CN1679525A CN 1679525 A CN1679525 A CN 1679525A CN 200510023272 CN200510023272 CN 200510023272 CN 200510023272 A CN200510023272 A CN 200510023272A CN 1679525 A CN1679525 A CN 1679525A
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Abstract
An oral disintegrating tablet of compound paracetamol is prepared from paracetamol, pseudoephedrine hydrochloride, dextromethorphan HBr, chlorphenamine maleate, filler, disintegrant, adhesive or moistening agent, lubricant, flavouring and pigment through direct tabletting.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to the oral cavity disintegration tablet dosage form, relate in particular to a kind of Aminodyne Compound oral cavity disintegration tablet that has the rapid release effect, good taste is arranged.
Background technology
Flu is modal frequently-occurring disease, and according to statistics, China has due to 36% worker student absent from duty and 67% system absent from school catches a cold.Flu has a strong impact on human orthobiosis and health, especially child, as untimely treatment, not only brings misery to child patient, also brings out other serious diseases easily.But the at present domestic antipyretic analgesic kind that is specifically designed to the child is few, the dosage form dullness, and clinical the needs increases more kind, can satisfy the requirement that different patients select medication.
Acetaminophen is clinical antipyretic analgesic commonly used, and various countries' pharmacopeia is all recorded, and its compound preparation is usually used in the treatment of cold, fever.The acetaminophen compound preparation kind of selling on the domestic market at present, mainly contains ordinary tablet, chewable tablet and oral solution.For child especially infant, swallowing whole tablets has difficulties usually.Though the oral solution taking convenience be difficult to cover the disagreeable taste of compound preparation, and stability of formulation is also relatively poor relatively.Chewable tablet can overcome above-mentioned shortcoming, but its hardness is big, and the compliance that the child takes medicine is relatively poor.
Oral cavity disintegration tablet (orally disintegrating tablet) is the novel solid quick releasing formulation of foreign study exploitation in recent ten years, compare with conventional tablet, this dosage form need not water and also need not to chew, and medicine places on the tongue, after meeting the rapid disintegrate of saliva, borrow swallowing act to go into the rapid onset of stomach.Therefore, the acetaminophen compound preparation is made oral cavity disintegration tablet will provide medicining mode very easily, have vast market prospect for the patient.
Summary of the invention
The objective of the invention is to overcome the deficiency of existing preparation variety, for the patient provides the effect of a kind of tool rapid release, the Aminodyne Compound oral cavity disintegration tablet of good taste is arranged.
Aminodyne Compound oral cavity disintegration tablet of the present invention comprises four kinds of principal agents, and wherein acetaminophen plays the effect of analgesic analgesic, and pseudoephedrine hydrochloride is a Decongestant, and dextromethorphan hydrobromide is a cough medicine, and chlorphenamine maleate is an antihistaminic.Described principal agent composition is respectively its original shape form or other pharmaceutically acceptable salts.Every content of dispersion of described oral cavity disintegration tablet is respectively: acetaminophen dosage 40-500mg, pseudoephedrine hydrochloride dosage 3.75-30mg, the right romilar dosage of hydrobromic acid 1.25-15mg, chlorphenamine maleate dosage 0.25-2mg.1 of each clinically administration is to several pieces.
Oral cavity disintegration tablet of the present invention also comprises effective auxiliary materials on the pharmaceutics except that principal agent, as filler, disintegrating agent, binding agent (wetting agent), lubricant, correctives and coloring agent.
In order to make tablet in the oral cavity, meet saliva disintegrate fast, select excellent disintegrating agent most important.Disintegrating agent of the present invention is selected from one or more in the following material: low-substituted hydroxypropyl cellulose (L-HPC), polyvinylpolypyrrolidone (PPVP), cross-linking sodium carboxymethyl cellulose (CCNa), crosslinked carboxymethyl fecula sodium (CCMS-Na) and gas-producing disintegrant.Its consumption be sheet heavy 0.5%～20%, wherein the consumption of L-HPC is preferably 2～15%, the consumption of PPVP is preferably 4～8%, the consumption of CCNa is preferably 3～8%, the consumption of CCMS-Na is preferably 4～8%, the consumption of gas-producing disintegrant is preferably 1～20%.
Filler of the present invention is selected from one or more in microcrystalline Cellulose (MCC), lactose, mannitol, erithritol, pregelatinized Starch, the starch.Its consumption be sheet heavy 40～80%, the applicable cases of other adjuvants is adjusted in the heavy and prescription according to sheet.
Binding agent of the present invention is selected from polyvidone, hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, ethyl cellulose or starch slurry, and its concentration is 2～20%.
Described wetting agent can be selected water or Different concentrations of alcohol.
Described lubricant is selected from magnesium stearate, Stepanol MG, Pulvis Talci or silicon dioxide, and its consumption is the routine dose of defined on the pharmaceutics.
In order to cover the bitterness of principal agent, make the oral cavity disintegration tablet good mouthfeel, Aminodyne Compound oral cavity disintegration tablet of the present invention adds following one or more correctivess: sweeting agent such as aspartame, stevioside, saccharin sodium, disodium glycyrrhizinate, sugar and derivant, polyhydric alcohol and derivant, and other natural and artificial sweetening agents, they can use separately or with the form of mixture.Aromatic can be one or more in Oleum menthae (brain), bitterness covering agent, the edible essence.Edible essence can be selected orange juice, Fructus Ananadis comosi, Fructus Fragariae Ananssae, Fructus Musae, Herba Menthae, Rhizoma et radix valerianae, fresh milk, chocolate essence etc., consumption be sheet heavy 0.1～5%.Essence can liquid or powder type add in the tablet.Mucilage plays a part the passivation taste bud, often share with sweeting agent.Can select gelatin, arabic gum, cellulose derivative etc.
In order to cover the bitter taste of dextromethorphan hydrobromide and chlorphenamine maleate, Aminodyne Compound oral cavity disintegration tablet of the present invention adds cyclodextrin and derivant thereof, as beta-schardinger dextrin-(β CD), HP-(HP β CD), methyl-beta-schardinger dextrin-(Me β CD), its consumption are the heavy 2-10% of sheet.Described two principal agents mode and cyclodextrin of form or mixture separately form clathrate, join in the tablet again.Conventional method is adopted in the preparation of cyclodextrin clathrate, as saturated solution method, ultrasonic method, polishing etc.
Aminodyne Compound oral cavity disintegration tablet of the present invention adopts art for coating to cover the bitterness of described four principal agents, and four kinds of principal agents can be distinguished coating, or carry out coating again after being mixed and made into medicine-containing particle earlier.Be used for coated granules and require to have bigger hardness, its particle diameter preferably in the scope of about 150-500 micron size, adopts methods such as centrifugal rotation granulation, high-speed stirred are granulated, extruding granulation to make the granule that meets the coating requirement.Coating material adopts on the pharmaceutics and is used for film-coated material, closes methacrylate copolymer (Eudragit RL) as hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), methylcellulose (MC), hydroxyethyl-cellulose (HEC), polyvinylpyrrolidone (PVP), aminoalkyl methacrylate copolymer (Eudragit E), ammonium.Generally be mixed with organic coating solution or aqueous dispersion coating solution and use, wherein the about 5-20% of the concentration of polymer.Also can add plasticizer, antiplastering aid, coloring agent and opacifier in the described coating solution.With the granule total weight, the rete of enwrapped granule weightening finish 5-80% can better cover the bitterness of principal agent, and the releasing properties of medicine is constant simultaneously.
In order to make tablet attractive in appearance, patient takes like a shot, and Aminodyne Compound oral cavity disintegration tablet of the present invention adds coloring agent, comprises natural and synthetic coloring agent.Selected color should be corresponding with edible essence, in the amount ranges that its consumption should allow to use in pharmaceutics.
The preparation of Aminodyne Compound oral cavity disintegration tablet of the present invention can be adopted direct compression process, and preparation technology is simple for this method, and is little to the harmful effect of disintegrate.But the performance requirement to flowability, compressibility and the tablet machine of adjuvant is higher.For overcoming the big and mobile relatively poor defective of this compound preparation principal agent amount, the preparation of Aminodyne Compound oral cavity disintegration tablet of the present invention also can be adopted wet granule compression tablet technology, promptly earlier with principal agent, in disintegrating agent and partially filled dose of mixing, make medicine-containing particle, again with medicine-containing particle and all the other filleies, add tabletting after disintegrating agent, correctives, the mix lubricant.Tablet hardness is controlled at 1.0-4.0kg.Our experiments show that gained tablet weight difference is little, the inside and outside disintegrate all meets the requirements, and mouthfeel is better, has reached intended purposes.
The specific embodiment:
Embodiment 1
Prescription
Acetaminophen 80mg
Pseudoephedrine hydrochloride 7.5mg
The right romilar 2.5mg of hydrobromic acid
Chlorphenamine maleate 0.5mg
Microcrystalline Cellulose (MCC) 200mg
Low-substituted hydroxypropyl cellulose (L-HPC) 23.1mg
Aspartame 1.6mg
Essence for organi juice 1.6mg
Magnesium stearate 3.2mg
Preparation: take by weighing each composition.Principal agent and adjuvant by the equivalent method mixing that progressively increases, are crossed 40 mesh sieves twice, add tabletting behind the magnesium stearate mixing.
Tablet hardness: 3-3.5kg, tablet weight variation :-2.59%～2.55%.
Adopt static method to measure the external disintegration of oral cavity disintegration tablet: tablet to be placed the small beaker that fills 2ml water (37 ± 1 ℃), use manual time-keeping simultaneously, measure the complete disintegrate required time of tablet.This tablet external disintegration: 50s.
Reference literature (Chem.Pharm.Bull., 2003,51 (10) 1121-1127) reported method is estimated the interior disintegration of body and the mouthfeel of oral cavity disintegration tablet: 6 healthy volunteers, getting a tablet at random for every places on the tongue, violent chewing can not be arranged, can not drink water, in the oral cavity, disperse required time fully with stopwatch record oral cavity disintegration tablet; Then medicated powder is spued and gargles, describe mouthfeel after the off-test: whether bitter sense is arranged, and whether sugariness is suitable, has or not grittiness etc. after the disintegrate.
The intraoral disintegration time limit: 48.5 ± 4.2s
Mouthfeel: grittiness is not obvious, and it is fragrant to taste orange, and the sweet taste deficiency is slightly bitter.
Embodiment 2
Prescription
Acetaminophen 40mg
Pseudoephedrine hydrochloride 3.75mg
The right romilar 1.25mg of hydrobromic acid
Chlorphenamine maleate 0.25mg
Microcrystalline Cellulose (MCC) 56mg
Mannitol 83.8mg
Polyvinylpolypyrrolidone (PVPP) 10mg
Aspartame 2mg
Fresh milk essence 1mg
Micropowder silica gel 2mg
Preparation: take by weighing each composition.Behind principal agent and adjuvant mix homogeneously, adopt the drift direct compression of 8mm.
Tablet hardness: 2.5kg, friability: 0.47%, external disintegration: 32s
Mouthfeel: grittiness is not obvious, and is earlier fragrant and sweet, can get one's bitters after tablet disperses fully.
Embodiment 3
Prescription
Acetaminophen 25%
Pseudoephedrine hydrochloride 2.34%
The right romilar 0.78% of hydrobromic acid
Chlorphenamine maleate 0.16%
Microcrystalline Cellulose (MCC) 25%
Mannitol 25.5%
Lactose 12.7%
Crosslinked carboxymethyl fecula sodium (CCMS-Na) 2%
Polyvinylpolypyrrolidone (PVPP) 3%
Stevioside 2%
Herba Menthae essence 0.5%
Magnesium stearate 1%
Preparation: take by weighing each composition.Behind principal agent and adjuvant mix homogeneously, direct compression.
Tablet hardness: 2.8～3.0kg, tablet weight variation :-3.27%～2.55%
External disintegration: 40s, the disintegration in the oral cavity: 38.3 ± 4.7s
Mouthfeel: the sweet taste foot, refrigerant sense is arranged after gargling, be difficult for tasting bitterness.
Embodiment 4
Prescription
Acetaminophen 500mg
Pseudoephedrine hydrochloride 30mg
The right romilar 15mg of hydrobromic acid
Chlorphenamine maleate 2mg
Corn starch 50mg
Cross-linking sodium carboxymethyl cellulose (CCNa) 24mg
Microcrystalline Cellulose (MCC) 124mg
Low-substituted hydroxypropyl cellulose (L-HPC) 31mg
Saccharin sodium 8mg
Flavoring pineapple essence 8mg
Magnesium stearate 8mg
The preparation: principal agent was pulverized 80 mesh sieves, get recipe quantity and corn starch and cross-linking sodium carboxymethyl cellulose mixing after, add water-wet system soft material, crossing 36 mesh sieves granulates, 70 ℃ of dryings, 36 mesh sieve granulate are with tabletting behind the uniform mixing such as granule and MCC, L-HPC, correctives, lubricant.
Tablet hardness: 2.5-3kg, tablet weight variation :-2.56%～2.60%, friability: 0.32%
External disintegration: 48s
Mouthfeel: grittiness is arranged slightly, and the sheet heart is a bit hard, and the sweet taste foot has Fructus Ananadis comosi perfume (or spice), bitterness slightly still after gargling.
This oral cavity disintegration tablet volume is bigger, is mainly used in the adult.
Embodiment 5
Prescription
Acetaminophen 24.2%
Pseudoephedrine hydrochloride 2.27%
The right romilar 0.76% of hydrobromic acid
Chlorphenamine maleate 0.15%
Pregelatinized Starch 7.58%
Anhydrous citric acid 1%
Erithritol 53.7%
Polyvinylpolypyrrolidone (PVPP) 5%
Sodium bicarbonate 1.36%
Strawberry essence 1%
Disodium glycyrrhizinate 2%
Color lake 0.5%
Magnesium stearate 0.5%
Preparation: principal agent and anhydrous citric acid were pulverized 80 mesh sieves.Take by weighing recipe quantity and pregelatinized Starch and an amount of color lake, the equivalent mixing that progressively increases, Dropwise 5 0% alcoholic solution is made soft material in right amount, cross 36 mesh sieve system granules, wet granular is crossed 36 mesh sieve granulate in 70 ℃ of dryings, after residue adjuvant mixed together in dried granule and the prescription, tabletting promptly.
Tablet hardness: 2.5-3kg, friability: 0.56%, tablet weight variation :-2.87%～4.49%
External disintegration: 24.3 ± 4.9s, the disintegration in the oral cavity: 29.5 ± 7.50s,
Mouthfeel: 6 volunteers represent that all mouthfeel can accept, and are sweeter, can taste the Fructus Fragariae Ananssae flavor, no grittiness.
Embodiment 6
Prescription
Acetaminophen 62.5%
Pseudoephedrine hydrochloride 3.75%
The right romilar 1.88% of hydrobromic acid
Chlorphenamine maleate 0.25%
Anhydrous citric acid 1%
Mannitol 16.35%
Polyvinylpolypyrrolidone (PVPP) 5%
Sodium bicarbonate 1%
Gelatin 1.17%
Essence for organi juice 1.5%
Herba Menthae essence 1.5%
Aspartame 3%
Color lake 0.6%
Magnesium stearate 0.5%
Preparation method is about to principal agent and anhydrous citric acid, mannitol and an amount of color lake mixing with embodiment 5, adds 50% alcoholic solution system soft material, crosses 36 mesh sieve system granules, 70 ℃ of dryings, and granulate, after residue adjuvant mixed together in dried granule and the prescription, tabletting is promptly.
Tablet hardness: 2.4～3.5kg, friability: 0.65%, external disintegration: 37s mouthfeel: fragrant and sweet flavor is obvious, and the back throat mouth that spues is a bit bitter, and the sheet heart is not hard.
Embodiment 7
Prescription
Acetaminophen 22.2%
Pseudoephedrine hydrochloride 2.08%
The right romilar 0.69% of hydrobromic acid
Chlorphenamine maleate 0.14%
Microcrystalline Cellulose (MCC) 23.6%
Mannitol 28.3%
Lactose 7.22%
Cross-linking sodium carboxymethyl cellulose (CCNa) 5%
Anhydrous citric acid 1.67%
Sodium bicarbonate 1.67%
Bitterness covering agent 1.5%
Essence for organi juice 3%
Stevioside 2%
Color lake 0.5%
Magnesium stearate 0.5%
Preparation: take by weighing each composition.Behind principal agent and adjuvant mix homogeneously, direct compression promptly.
Tablet hardness: 2-2.5kg, external disintegration: 27 ± 1.3s
Mouthfeel: orange is obviously fragrant, and is sweet, and tablet has caramel after collapsing and loosing, and does not have bitterness sense.
Embodiment 8
Prescription
Acetaminophen 22.2%
Pseudoephedrine hydrochloride 2.08%
The right romilar 0.69% of hydrobromic acid
Chlorphenamine maleate 0.14%
Beta-schardinger dextrin-(β CD) 2.78%
Mannitol 35.3%
Microcrystalline Cellulose (MCC) 22.9%
Cross-linking sodium carboxymethyl cellulose (CCNa) 5%
Anhydrous citric acid 1.67%
Sodium bicarbonate 1.67%
Vanilla 2%
Saccharin sodium 2%
Color lake 0.6%
Micropowder silica gel 1%
Preparation: prepare the saturated aqueous solution of β CD earlier, add right romilar of hydrobromic acid and chlorphenamine maleate respectively, the stirring at room certain hour forms until inclusion.The content of two principal agents in filtration, drying, the mensuration clathrate.Clathrate was pulverized 80 mesh sieves, take by weighing recipe quantity, behind all the other adjuvant mix homogeneously in the prescription, direct compression promptly.
Mouthfeel: the sheet heart is slightly hard, does not have grittiness, delicate fragrance relatively, bitterness slightly after gargling.
Embodiment 9
Prescription
Acetaminophen 17.8%
Pseudoephedrine hydrochloride 1.67%
The right romilar 0.56% of hydrobromic acid
Chlorphenamine maleate 0.11%
HP-(HP β CD) 4.44%
Mannitol 40.5%
Lactose 17.4%
Polyvinylpolypyrrolidone (PVPP) 5%
Anhydrous citric acid 2%
Sodium bicarbonate 2%
Bitterness covering agent 1.2%
Chocolate essence 3.5%
Aspartame 2.2%
Color lake 0.6%
Stepanol MG 1%
Preparation: right romilar of hydrobromic acid and chlorphenamine maleate were pulverized 80 mesh sieves, get a certain amount of and HP β CD mixing, place mortar, start grinder and grind certain hour, until can not taste bitterness (place on the tongue 1～2min), show medicine by enclose in HP β CD.Take by weighing recipe quantity, with all the other auxiliary materials and mixing in the prescription, direct compression promptly.
Tablet hardness: 1.5-2kg, external disintegration: 23 ± 1.7s
Mouthfeel: the sheet heart is not hard, and no grittiness is chocolate flavoured obvious, no bitterness.
Embodiment 10
Prescription 0
Coated granule prescription (by 1000)
Acetaminophen 80g
Hydroxypropyl emthylcellulose/Polyethylene Glycol (Opadry) 15g
Silica 1 .2g
Titanium dioxide colorant 0.5g
Distilled water 133ml
Preparation: 15g hydroxypropyl emthylcellulose/Polyethylene Glycol dispersion coating material, 1.2g silicon dioxide and 0.5g titanium dioxide colorant are dispersed in the 133ml water, and homogenize prepares the coating suspension.
Acetaminophen is sieved, getting particle diameter places fluidized bed plant (for example at the granule of 150-500 micron (being the 30-100 order), Glatt GPCG1 type) fluidisation in is carried out fluidized coating with the suspended substance atomisation pressure of about 3-5g/ minute spray velocity and 1-1.5bar.It is about 15% that last coating membrane increases weight, granulate, and it is standby to get the following granule of 40 orders.
In kind other three principal agents are carried out coating.
The prescription of oral cavity disintegration tablet:
Coated granule 26%
Erithritol 56.8%
Microcrystalline Cellulose (MCC) 3.75%
Low-substituted hydroxypropyl cellulose (L-HPC) 3.75%
Polyvinylpolypyrrolidone (PVPP) 5%
Herba Menthae essence 1.5%
Aspartame 1.5%
Color lake 0.75%
Magnesium stearate 1%
Preparation: behind the adjuvant mix homogeneously in coated granule and the prescription, direct compression promptly.
Tablet hardness: 1.5-2kg, external disintegration: 22.3 ± 2.1s, disintegration in the oral cavity: 31.5 ± 3.2s
Mouthfeel: there is not bitterness, fragrant and sweet moderate, grittiness slightly.
Embodiment 11
Prescription
Medicine-containing particle prescription: (by 1000)
Acetaminophen 80g
Pseudoephedrine hydrochloride 7.5g
The right romilar 2.5g of hydrobromic acid
Chlorphenamine maleate 0.5g
Microcrystalline Cellulose 20g
Polyethylene pyrrole Lip river alkane ketone (k30) 3.5g
Preparation: respectively principal agent and microcrystalline Cellulose are crossed 100 mesh sieves, get recipe quantity,, add and stir the system soft material in the said mixture, cross 30 mesh sieve system granules with polyvinylpyrrolidone 20% the solution of making soluble in water by the equivalent method mixing that progressively increases.70 ℃ of dryings, granulate.Get particle diameter 30-100 purpose medicine-containing particle and carry out coating.
The coated granule prescription:
Medicine-containing particle 114g
Eudragit?E?PO 22.8g
Sodium lauryl sulphate 1.6g
Dibutyl sebacate 3.42g
Pulvis Talci 5.7g
Color lake 100mg
Titanium dioxide 400mg
Distilled water 194ml
Preparation: the water of about 1/2 amount is placed beaker, add sodium lauryl sulphate and dibutyl sebacate and stir evenly, under agitation slowly add Eudragit E PO, continue to stir 2h; Pulvis Talci, color lake, titanium dioxide are added in the entry high speed homogenize 5min in addition; Adjuvant suspensions such as Pulvis Talci are poured in the Eudragit E PO aqueous dispersions, stirred evenly.
Medicine-containing particle is placed fluidized bed plant (smart DPL-0.5) fluidisation, carry out fluidized coating with the suspended substance atomisation pressure of about 3-5g/ minute spray velocity and 1-1.5bar.It is about 20% that last coating membrane increases weight, granulate, and it is standby to get the following granule of 40 orders.
Orally disintegrating tablet prescription:
Coated granule 30.4%
Mannitol 53.2%
Microcrystalline Cellulose (MCC) 3.33%
Low-substituted hydroxypropyl cellulose (L-HPC) 3.33%
Cross-linking sodium carboxymethyl cellulose (CCNa) 4%
Essence for organi juice 2%
Aspartame 2%
Color lake 0.78%
Magnesium stearate 1%
Preparation: behind the adjuvant mix homogeneously in coated granule and the prescription, direct compression promptly.
Tablet hardness: 1.5-2kg, external disintegration: 20s
Mouthfeel: do not have the sheet heart, fragrant and sweet obviously, grittiness slightly.
Embodiment 12
Prescription medicine-containing particle prescription: (by 1000)
Acetaminophen 80g
Pseudoephedrine hydrochloride 7.5g
The right romilar 2.5g of hydrobromic acid
Chlorphenamine maleate 0.5g
Corn starch 20g
Hydroxypropyl emthylcellulose 1.0g
Preparation: principal agent was pulverized 100 mesh sieves, got recipe quantity and corn starch mixing, and hydroxypropyl emthylcellulose was dissolved in 50% the ethanol and makes 6% solution, and added and stir the system soft material in the said mixture, 30 mesh sieve system granules.70 ℃ of dry 2-3h, granulate.Get particle diameter 30-100 purpose medicine-containing particle and carry out coating.
The coated granule prescription:
Medicine-containing particle 111.5g
Eudragit?RL?30D 44.6g
Sodium carboxymethyl cellulose 1.49g
Tween 80 3.01g
Polyethylene glycol 6000 1.49g
Pulvis Talci 7.43g
Color lake 200mg
Titanium dioxide 800mg
Distilled water 164ml
Preparation: Tween 80 (be made in advance 33% aqueous solution) is added in the suitable quantity of water, adds sodium carboxymethyl cellulose, stirring and dissolving stirs and slowly adds Eudragit RL 30D down, continues to stir 30min; In addition all the other adjuvants are added in the surplus water, the high speed homogenize is with this suspension and above-mentioned Eudragit RL aqueous dispersion mixing.
Medicine-containing particle is placed the fluidized bed plant fluidisation, carry out fluidized coating with the suspended substance atomisation pressure of about 3-5g/ minute spray velocity and 1-1.5bar.It is about 40% that last coating membrane increases weight, granulate, and it is standby to get the following granule of 40 orders.
Orally disintegrating tablet prescription:
Coated granule 34.7%
Mannitol 41%
Lactose 10.3%
Cross-linking sodium carboxymethyl cellulose (CCNa) 4%
Polyvinylpolypyrrolidone (PVPP) 4%
Strawberry essence 2%
Stevioside 2.22%
Color lake 0.78%
Magnesium stearate 1%
Preparation: behind the adjuvant mix homogeneously in coated granule and the prescription, adopt 12mm drift direct compression.
Tablet hardness: 1.3-2kg, external disintegration: 21 ± 1.5s, disintegration in the oral cavity: 27.1 ± 3.5s
The external stripping quantity of stripping situation: 15min is near 100%.
Mouthfeel: fragrant and sweet obvious, there is not bitterness, slightly grittiness.
The present invention describes by above description and embodiment, more than is described as nonrestrictively, does not limit claim scope of the present invention.
Claims (16)
1, a kind of Aminodyne Compound oral cavity disintegration tablet, it is characterized in that described oral cavity disintegration tablet contains the principal agent acetaminophen, pseudoephedrine hydrochloride, dextromethorphan hydrobromide and chlorphenamine maleate, and effective auxiliary materials comprises filler, disintegrating agent, binding agent or wetting agent, lubricant, correctives and coloring agent on the pharmaceutics, described disintegrating tablet wherein every content of dispersion is respectively: acetaminophen 40-500mg, pseudoephedrine hydrochloride 3.75-30mg, the right romilar 1.25-15mg of hydrobromic acid, chlorphenamine maleate 0.25-2mg; Contain disintegrating agent and be sheet heavy 0.5%～20%; Contain correctives and be sheet heavy 0.1～10%.
2, by the described oral cavity disintegration tablet of claim 1, it is characterized in that wherein said disintegrating agent is selected from one or more of low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium or gas-producing disintegrant.
3, by the described oral cavity disintegration tablet of claim 2, wherein said disintegrating agent wherein the consumption of low-substituted hydroxypropyl cellulose be sheet heavy 2～15%, the consumption of polyvinylpolypyrrolidone be sheet heavy 4～8%, the consumption of cross-linking sodium carboxymethyl cellulose be sheet heavy 3～8%, the consumption of crosslinked carboxymethyl fecula sodium be sheet heavy 4～8%, the consumption of gas-producing disintegrant be sheet heavy 1～20%.
4, by the described oral cavity disintegration tablet of claim 1, it is characterized in that described filler is selected from one or more in microcrystalline Cellulose, lactose, mannitol, erithritol, pregelatinized Starch, the starch, its consumption be sheet heavy 40～80%.
5, by the described oral cavity disintegration tablet of claim 1, it is characterized in that described binding agent is selected from polyvidone, hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, ethyl cellulose or starch slurry, its concentration is 2～20%; Described wetting agent is selected from water or Different concentrations of alcohol.
6, by the described oral cavity disintegration tablet of claim 1, it is characterized in that described lubricant is selected from magnesium stearate, Stepanol MG, Pulvis Talci or silicon dioxide, its consumption is the routine dose of defined on the pharmaceutics.
7, by the described oral cavity disintegration tablet of claim 1, it is characterized in that adopting sweeting agent and aromatic or/and mucilage or/and the preparation clathrate, or/and coating is covered the bitterness of principal agent.
8, by the described oral cavity disintegration tablet of claim 7, it is characterized in that described sweeting agent is selected from aspartame, stevioside, saccharin sodium, disodium glycyrrhizinate, sugar and derivant, polyhydric alcohol and derivant or other natural and artificial sweetening agents, its type of service is independent or mixture.
9, by the described oral cavity disintegration tablet of claim 7, it is characterized in that described aromatic is selected from one or more in Oleum menthae (brain), bitterness covering agent or the edible essence, wherein edible essence is selected from orange juice, Fructus Ananadis comosi, Fructus Fragariae Ananssae, Fructus Musae, Herba Menthae, Rhizoma et radix valerianae, fresh milk or chocolate essence, consumption be sheet heavy 0.1～5%; Add tablet with liquid or powder type.
10, by the described oral cavity disintegration tablet of claim 7, it is characterized in that described mucilage is selected from gelatin, arabic gum or cellulose derivative.
11, by the described oral cavity disintegration tablet of claim 7, it is characterized in that described clathrate adopts cyclodextrin and derivant and dextromethorphan hydrobromide and chlorphenamine maleate formation, wherein cyclodextrin and derivant thereof are selected from beta-schardinger dextrin-(β CD), HP-(HP β CD) or methyl-beta-schardinger dextrin-(Me β CD), its consumption are the heavy 2-10% of sheet.
12, by the described oral cavity disintegration tablet of claim 7, it is characterized in that described coating, its technology is coating again for coating respectively or after being mixed and made into medicine-containing particle earlier.
13, by the described oral cavity disintegration tablet of claim 12, it is characterized in that described coated granules, its particle diameter is the 150-500 micron.
14, by the described oral cavity disintegration tablet of claim 12, it is characterized in that described coating, its coating material is selected from hydroxypropyl emthylcellulose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl-cellulose, polyvinylpyrrolidone, aminoalkyl methacrylate copolymer or ammonium and closes methacrylate copolymer, the rete weightening finish 5-80% of described enwrapped granule.
15, by the described oral cavity disintegration tablet of claim 1, it is characterized in that adding coloring agent in the described oral cavity disintegration tablet, comprise natural and synthetic coloring agent, its consumption is the scope that pharmaceutics allows use.
16, by the preparation method of the described oral cavity disintegration tablet of claim 1, it is characterized in that adopting direct compression process or wet granule compression tablet method.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510023272 CN1679525A (en) | 2005-01-12 | 2005-01-12 | Oral disintegrant of compound paracetamol |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510023272 CN1679525A (en) | 2005-01-12 | 2005-01-12 | Oral disintegrant of compound paracetamol |
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| CN1679525A true CN1679525A (en) | 2005-10-12 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200510023272 Pending CN1679525A (en) | 2005-01-12 | 2005-01-12 | Oral disintegrant of compound paracetamol |
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100358523C (en) * | 2006-01-24 | 2008-01-02 | 杭州民生药业集团有限公司 | Preparation method of paracetamol pseudoephedrine hydrochloride and cholrphenamine maleate oral disintegration tablet |
| CN101596157A (en) * | 2008-06-04 | 2009-12-09 | 北京科信必成医药科技发展有限公司 | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan |
| CN101143138B (en) * | 2006-09-11 | 2010-06-16 | 上海玉安药业有限公司 | Paracetamol and pseudoephedrine hydrochloride tablets made by dry powder direct tabletting |
| CN101801349A (en) * | 2007-09-24 | 2010-08-11 | 宝洁公司 | Composition and method of stabilized sensitive ingredient |
| CN103156849A (en) * | 2013-03-21 | 2013-06-19 | 青岛正大海尔制药有限公司 | Compound pseudoephedrine hydrochloride enteric-coated tablet and preparation method thereof |
| 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 |
| CN103181907A (en) * | 2011-12-31 | 2013-07-03 | 天津市嵩锐医药科技有限公司 | Chlorpheniramine maleate medicine composition |
| CN101879141B (en) * | 2009-05-05 | 2013-07-17 | 烟台绿叶动物保健品有限公司 | Taste-masking tilmicosin gastric-soluble particle preparation |
| CN104606232A (en) * | 2015-02-04 | 2015-05-13 | 上海华源安徽仁济制药有限公司 | Artificial cowbezoar and chlorpenaleate capsule and preparation method thereof |
| CN110731945A (en) * | 2018-07-18 | 2020-01-31 | 北京万全德众医药生物技术有限公司 | Memantine hydrochloride orally disintegrating tablet and its preparation method |
| US11202756B2 (en) | 2018-04-18 | 2021-12-21 | Shilpa Medicare Limited | Oral disintegrating film compositions of paracetamol |
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- 2005-01-12 CN CN 200510023272 patent/CN1679525A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100358523C (en) * | 2006-01-24 | 2008-01-02 | 杭州民生药业集团有限公司 | Preparation method of paracetamol pseudoephedrine hydrochloride and cholrphenamine maleate oral disintegration tablet |
| CN101143138B (en) * | 2006-09-11 | 2010-06-16 | 上海玉安药业有限公司 | Paracetamol and pseudoephedrine hydrochloride tablets made by dry powder direct tabletting |
| CN101801349A (en) * | 2007-09-24 | 2010-08-11 | 宝洁公司 | Composition and method of stabilized sensitive ingredient |
| CN101596157A (en) * | 2008-06-04 | 2009-12-09 | 北京科信必成医药科技发展有限公司 | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan |
| CN101879141B (en) * | 2009-05-05 | 2013-07-17 | 烟台绿叶动物保健品有限公司 | Taste-masking tilmicosin gastric-soluble particle preparation |
| 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 |
| CN103181907A (en) * | 2011-12-31 | 2013-07-03 | 天津市嵩锐医药科技有限公司 | Chlorpheniramine maleate medicine composition |
| CN103156849A (en) * | 2013-03-21 | 2013-06-19 | 青岛正大海尔制药有限公司 | Compound pseudoephedrine hydrochloride enteric-coated tablet and preparation method thereof |
| CN104606232A (en) * | 2015-02-04 | 2015-05-13 | 上海华源安徽仁济制药有限公司 | Artificial cowbezoar and chlorpenaleate capsule and preparation method thereof |
| US11202756B2 (en) | 2018-04-18 | 2021-12-21 | Shilpa Medicare Limited | Oral disintegrating film compositions of paracetamol |
| CN110731945A (en) * | 2018-07-18 | 2020-01-31 | 北京万全德众医药生物技术有限公司 | Memantine hydrochloride orally disintegrating tablet and its preparation method |
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