CN101596158B - Compound slow release preparation of acetyl aminophenol, pseudoephedrine and dextromethorphan - Google Patents
Compound slow release preparation of acetyl aminophenol, pseudoephedrine and dextromethorphan Download PDFInfo
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- CN101596158B CN101596158B CN2008101145746A CN200810114574A CN101596158B CN 101596158 B CN101596158 B CN 101596158B CN 2008101145746 A CN2008101145746 A CN 2008101145746A CN 200810114574 A CN200810114574 A CN 200810114574A CN 101596158 B CN101596158 B CN 101596158B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 62
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 229960001985 dextromethorphan Drugs 0.000 title claims abstract description 35
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- 229960003908 pseudoephedrine Drugs 0.000 title claims abstract description 23
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 title claims description 11
- ADVGKWPZRIDURE-UHFFFAOYSA-N 2'-Hydroxyacetanilide Chemical compound CC(=O)NC1=CC=CC=C1O ADVGKWPZRIDURE-UHFFFAOYSA-N 0.000 title abstract description 3
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a slow release preparation taking acetyl aminophenol, pseudoephedrine or physiologically acceptable slat thereof and dextromethorphan or physiologically acceptable slat thereof as active ingredients. The slow release preparation is characterized in that a releasing system comprises a tablet core and/or pill core capable of enabling a medicament to slowly release and a coating, wherein one part and/or all of the active ingredients exist in the tablet core and/or pill core, and the rest of the active ingredients exist in the coating.
Description
Technical field
The present invention relates to a kind of slow releasing preparation that is active component with acetaminophen, pseudoephedrine or its physiologically acceptable salt and dextromethorphan or its physiologically acceptable salt, belong to field of medicaments.
Background technology
Flu is the upper respiratory tract mucosa infection that is caused by a lot of dissimilar viruses, and its cardinal symptom often is nasal obstruction, sneeze, dry cough, slight throat pain and heating etc., and systemic symptom has whole body discomfort, headache and myalgia etc.Because of no specific therapy can be sayed,, can only adopt symptomatic treatment to impel many remissions of flu so virus is firm then unnecessary.Because therefore the many symptoms that also do not have a kind of agents alleviate and deposit have various compound preparations to go on the market successively.These compound preparations select for use the medicine composition compound recipe of different curative effects to be used to alleviate simultaneous different symptoms.There is multiple symptom as patient,, then suits the medicine to the illness and use suitable compound preparation than more suitable with several individual event medicines, also more economical sometimes particularly at common cold initial stage.
Acetaminophen is an acetophenone amine dipron thing.By suppressing Cycloxygenase, improve the threshold of pain and produce analgesic activity, selectivity suppresses the synthetic of hypothalamus thermotaxic centre prostaglandin, cause peripheral blood vessel expansion, perspire and reach refrigeration function, its refrigeration function intensity is suitable with aspirin, but can generation with aspirin and contain the relevant side effect of aspirin product.By suppressing the synthetic of prostaglandin etc. and discharge, improve the threshold of pain and play analgesic activity, belong to the periphery analgesic, effect is than a little less than the aspirin, only to light, moderate pain is effective.This product does not have the obvious anti-inflammatory and anti effect.
Pseudoephedrine claims d-pseudephedrine again, is the optical isomer of ephedrine, and the two is by extracting gained in Herba Ephedrae or the ephedra equisetina grass, but synthetic at present.Pseudoephedrine discharges norepinephrine by stimulating SNE, play sympatheticomimetic action indirectly, its preventing respiratory is identical with the effect and the ephedrine of nasal congestion, but boosting only is 1/5 of an ephedrine, strengthening heart rate and pressor effect only is 1/4 of ephedrine, aspect the expansion bronchus smooth muscle only be its 1/2.The pseudoephedrine vasoconstrictive has certain selectivity, mainly shrinks the upper respiratory tract blood vessel and makes and breathe unobstructedly, is used to shrink nasal mucosa vessels alleviating the nasal obstruction symptom, and is evident in efficacy and side effect is little, in the use usually with its hydrochlorate or sulfate.
Dextromethorphan has another name called dextro-methorphan, goes on the market in the U.S. in 1954.Its does not have anesthesia through strict and animal experiment and clinical research widely proves that its curative effect certainly, seldom has side effects, and is the most widely used cough medicine in the world." dextromethorphan is a kind of cough medicine that replaces codeine " thought by The World Health Organization (WHO) in 1989.Dextromethorphan has been widely used abroad clinically because of it has characteristics such as potent, long-acting, safe, now state's pharmacopeia such as existing American and Britain, Japan and Italy are recorded, dextromethorphan is very easily by gastrointestinal absorption, oral 10～the 30min of ordinary tablet begins to play a role, maximum appears in 2h left and right sides blood drug level, and plasma half-life is 2～3h.It by liver metabolism or with original shape and metabolite form from renal excretion, its main metabolites is nor-dextromethorphan.Because the dextromethorphan half-life is short, general dosage is 15～30mg, an administration 3～4 times day by day, and blood concentration fluctuation is bigger, easily causes side effect.During using, it uses its hydrobromate usually.
Acetaminophen, pseudoephedrine, dextromethorphan are prepared into slow releasing preparation, can overcome the relevant symptom of flu comprehensively, comprise simultaneously symptoms such as obturation with pain and heating, sneeze.Because acetyl aminophenol, pseudoephedrine, dextromethorphan using dosage, rate of release, the difference of aspects such as absorbance need provide a kind of three of making to discharge, absorb and reach synchronous, so that better play synergistic compound preparation, reduce the medication number of times and make things convenient for patient's medication.
Summary of the invention
The purpose of this invention is to provide and a kind ofly can overcome the relevant symptom of flu comprehensively, and all active component all are the compound preparation that slow release discharges.Technical solution of the present invention is as follows:
The slow releasing preparation that is active component with acetaminophen, pseudoephedrine or its physiologically acceptable salt, dextromethorphan or its physiologically acceptable salt of the present invention, comprise delivery system, described delivery system is made up of the label that drug slow is discharged and/or ball core and coating, a described active component part is present in label and/or the ball core, and the residual activity composition is present in the coating.Described acetaminophen, pseudoephedrine or its physiologically acceptable salt and dextromethorphan or its physiologically acceptable salt all are slow release and discharge.Described " part ", can be one of in three kinds of active component or two, or one of in three kinds of active component or two or three in a part.Slow releasing preparation of the present invention in every single dosage unit, contains acetaminophen 10-1000mg, pseudoephedrine or its physiologically acceptable salt 5-90mg, dextromethorphan or its physiologically acceptable salt 1-120mg.As preferably, contain acetaminophen 200-1000mg in each dosage unit, pseudoephedrine or its physiologically acceptable salt 20-90mg, dextromethorphan or its physiologically acceptable salt 10-50mg.
The physiologically acceptable salt of pseudoephedrine of the present invention comprises acylate or inorganic acid salt, wherein is preferably hydrochlorate or sulfate; The physiologically acceptable salt of described dextromethorphan comprises acylate or inorganic acid salt, wherein is preferably hydrobromate.
As preferred version of the present invention, described acetaminophen release characteristic is: 2h (10-30%), 4h (20-50%), 8h (being not less than 50%).
As preferred version of the present invention, the release characteristic of described pseudoephedrine or its physiologically acceptable salt is: 1h (20-65%), 2h (42-85%), 4h (60-90%), 8h (being not less than 70%).
As preferred version of the present invention, described dextromethorphan or its physiologically acceptable salt release characteristic are: 2h (30-60%), 4h (45-70%), 8h (being not less than 70%).
Label of the present invention or ball core can be by hydroxypropyl methylcellulose, polyvinylpyrrolidone, ethyl cellulose, methylcellulose, Hydroxypropyl Methylcellulose Phathalate, cellulose acetate-phthalate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, hexadecanol, Rikemal B 200, stearic acid, glyceryl monostearate, Brazil wax, hydroxy methocel, polyvinyl alcohol, poly-phthalic acid vinyl acetate, polystyrene, carbopol, polrvinyl chloride, octadecanol, diethyl phthalate, dioctyl phthalate, Polyethylene Glycol, sodium alginate, chitosan, gelatin, Lac, pectin, guar gum, sucrose, lactose, starch, dextrin, Icing Sugar, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose, mannitol, microcrystalline Cellulose, pregelatinized Starch, in the titanium dioxide one or more are made.
Coating material of the present invention, one or more in can being compared by ethyl cellulose, starch, Aquacoat, methylcellulose, cellulose acetate, acrylic resin, Opadry, Su Li are made.
Slow releasing preparation of the present invention as required, can be tablet, granule, pill, capsule, suspensoid etc.
Slow releasing preparation of the present invention as required, can add lubricant, and described lubricant can and month be hung in the pure magnesium sulfate one or more for magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols.
Slow releasing preparation of the present invention, can not only overcome the relevant symptom of flu comprehensively, the performance synergistic interaction effect of compound drugs, and the release of three kinds of active component of slow releasing preparation of the present invention, absorb and to reach synchronously, it obtains desired drug release behavior in vivo and in vitro.Such drug release behavior can reduce takes number of times (by original 4 times on the one reduce to a day twice, promptly take night and morning).Therefore this preparation has the advantages that the medication number of times is few, medicine slowly discharges in vivo, blood drug level is steady, fluctuation is little, bioavailability is high, safe.
The specific embodiment
By following examples the slow releasing preparation that is active component with acetaminophen, pseudoephedrine or its physiologically acceptable salt and dextromethorphan or its physiologically acceptable salt of the present invention is done further to specify, but not as limitation of the present invention.
Embodiment 1
Prescription:
| Acetaminophen | 250g |
| Pseudoephedrine hydrochloride | 90g |
| Hydroxypropyl methylcellulose K4M | 6g |
| Hydroxypropyl methylcellulose E5 | 60g |
| Microcrystalline Cellulose | 36g |
| 10% 30 POVIDONE K 30 BP/USP 30Aqueous solution | In right amount |
The coating prescription:
| Dextromethorphan hydrobromide | 30g |
| Ethyl cellulose | 30g |
| Ethanol | Add to 1000ml |
Preparation method:
(1) particulate preparation hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose E5 microcrystalline Cellulose are crossed 80 mesh sieves respectively, with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen and pseudoephedrine hydrochloride mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate, standby.
(2) preparation of coating solution is got dextromethorphan hydrobromide and is dissolved in the ethanol, adds ethyl cellulose, and mix homogeneously is standby.
(3) get (1) granule and carry out coating, obtain coated granule.
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet.
(5) in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, gets final product coated tablet.
(6) get (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
(7) get (3) gained granule direct packaging, promptly get granule.
The release characteristic of active component is as shown in table 1 in the gained different dosage form.
The release characteristic of active component in table 1 different dosage form
Embodiment 2
Prescription:
| Acetaminophen | 240g |
| Pseudoephedrine hydrochloride | 50g |
| Hydroxypropyl methylcellulose K4M | 6g |
| Hydroxypropyl methylcellulose E5 | 75g |
| Microcrystalline Cellulose | 45g |
| 10% 30 POVIDONE K 30 BP/USP 30Aqueous solution | In right amount |
The coating prescription:
| Pseudoephedrine hydrochloride | 50g |
| Dextromethorphan hydrobromide | 20g |
| Cellulose acetate | 70.5g |
| Water | An amount of to dissolving fully |
Preparation method:
(1) particulate preparation hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose E5, microcrystalline Cellulose are crossed 80 mesh sieves respectively, with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen and pseudoephedrine hydrochloride mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate, standby.
(2) preparation of coating solution is got dextromethorphan hydrobromide and pseudoephedrine hydrochloride is soluble in water, adds cellulose acetate, and mix homogeneously is standby.
(3) get (1) granule and carry out coating, obtain coated granule.
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet.
(5) in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, gets final product coated tablet.
(6) get (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
(7) get (3) gained granule direct packaging, promptly get granule.
The release characteristic of active component is as shown in table 2 in the gained different dosage form.
The release characteristic of active component in table 2 different dosage form
Embodiment 3
Prescription:
| Acetaminophen | 250g |
| Pseudoephedrine sulfate | 40g |
| Dextromethorphan hydrobromide | 20g |
| Hydroxypropyl methylcellulose K100M | 10g |
| Hydroxyethyl-cellulose | 72g |
| Microcrystalline Cellulose | 50g |
| 10% 30 POVIDONE K 30 BP/USP 30Aqueous solution | In right amount |
The coating prescription:
| Pseudoephedrine sulfate | 50g |
| Dextromethorphan hydrobromide | 10g |
| Cellulose diacetate | 35g |
| Ethanol | An amount of to dissolving fully |
Preparation method:
(1) particulate preparation hydroxypropyl methylcellulose K100M, hydroxyethyl-cellulose, microcrystalline Cellulose, cross 80 mesh sieves respectively, with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen, dextromethorphan hydrobromide and pseudoephedrine sulfate mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 50 ℃ of dryings, 20 mesh sieve granulate, standby.
(2) preparation of coating solution is got dextromethorphan hydrobromide and pseudoephedrine sulfate is dissolved in the ethanol, adds cellulose diacetate, and mix homogeneously is standby.
(3) get (1) granule and carry out coating, obtain coated granule.
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet.
(5) in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, gets final product coated tablet.
(6) get (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
(7) get (3) gained granule direct packaging, promptly get granule.
The release characteristic of active component is as shown in table 3 in the gained different dosage form.
The release characteristic of active component in table 3 different dosage form
Embodiment 4
Prescription:
| Acetaminophen | 325g |
| Pseudoephedrine hydrochloride | 90g |
| Dextromethorphan hydrobromide | 30g |
| Celphere | 150g |
| Hydroxypropyl methylcellulose E5 | 6g |
| Sulisi aqueous dispersion (solid content 25%) | 80g |
| The water solublity coating powder | 5g |
| Titanium dioxide | 5g |
| Stearic acid | 5g |
| 30 POVIDONE K 30 BP/USP 30 | In right amount |
| Water | In right amount |
| Dehydrated alcohol | In right amount |
The coating prescription:
| Opadry | 30g |
| Pure water | Add to 1000ml |
Preparation method:
(1) acetaminophen slow-release micro-pill preparation
I, an amount of 30 POVIDONE K 30 BP/USP 30 is added an amount of dehydrated alcohol be made into 5% (w/w) solution, standby;
II, stearic acid is added an amount of dehydrated alcohol be mixed with 5% (w/w) solution, standby;
III, get an amount of recipe quantity celphere and put in the coating pan;
IV, take by weighing the stearic acid ethanol solution for preparing and be sprayed on the celphere;
V, spray 30 POVIDONE K 30 BP/USP 30 ethanol solutions successively, the hydrojet intermission also adds acetaminophen, treats that acetaminophen adheres to the ball wicking surface and repeats said process again, finishes until adding powder;
VI, take out and to make micropill in 35 ℃ of dryings 12 hours;
VII, sieve with 14 mesh sieves and 20 orders.
Promptly get the acetyl slow-release micro-pill, standby.
(2) pseudoephedrine hydrochloride slow release micropill
I, preparation 10%HPMC E5 aqueous solution, standby;
II, get the Sulisi aqueous dispersion and add water, shake up standby;
III, preparation contain the water solublity coating solution of water solublity coating powder 10%, titanium dioxide 1%;
IV, preparation 40% pseudoephedrine hydrochloride aqueous solution add above-mentioned HPMC solution again, stir evenly standby;
V, get the celphere coating, spray step IV gained solution is collected micropill to finishing;
VI, to pseudoephedrine hydrochloride micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again.
Promptly get pseudoephedrine hydrochloride medicine-feeding micropill, standby.
(3) dextromethorphan slow-release micro-pill
According to (2) technology, be equipped with the dextromethorphan slow-release micro-pill with legal system.
(4) preparation of coating solution: 30g adds in the pure water with Opadry, and adds pure water to 100ml, stirs 1 hour.
(5) get (1), (2) (3) micropill carries out coating, obtains coated granule.
(6) in (5) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet.
(7) in (1), (2) (3) gained micropill, add an amount of magnesium stearate, mix homogeneously, tabletting is got (4) coating solution, is wrapped in outside the tablet, gets final product coated tablet.
(8) get (1), (2) (3) gained particle packing in the hungry area softgel shell, promptly get capsule.
(9) get (1), (2) (3) gained granule direct packaging, promptly get granule.
The release characteristic of active component is as shown in table 4 in the gained different dosage form.
The release characteristic of active component in table 4 different dosage form
Embodiment 5
Prescription:
| Acetaminophen | 325g |
| Pseudoephedrine hydrochloride | 90g |
| Dextromethorphan hydrobromide | 30g |
| Celphere | 20g |
| Hydroxypropyl methylcellulose K4M | 7g |
| Hydroxypropyl methylcellulose E5 | 6g |
| Microcrystalline Cellulose | 42g |
| Pregelatinized Starch | 21g |
| Sulisi aqueous dispersion (solid content 25%) | 80g |
| Light water dissolubility coating powder | 5g |
| Titanium dioxide | 5g |
| 10% 30 POVIDONE K 30 BP/USP 30Aqueous solution | In right amount |
| Water | In right amount |
| Magnesium stearate | 3g |
| Dehydrated alcohol | In right amount |
The coating prescription:
| Opadry | In right amount |
| Pure water | Add to 1000ml |
Preparation method:
(1) the plain sheet preparation of acetaminophen slow release
With recipe quantity hydroxypropyl methylcellulose K
4With the mixed powder of pregelatinized Starch, microcrystalline Cellulose with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate add the magnesium stearate mixing, tabletting, promptly;
(2) pseudoephedrine hydrochloride slow release micropill
I, preparation 10%HPMC E5 aqueous solution, standby;
II, get the Sulisi aqueous dispersion and add water, shake up standby;
III, preparation contain the water solublity coating solution of water solublity coating powder 10%, titanium dioxide 1%;
IV, preparation 40% pseudoephedrine hydrochloride aqueous solution add above-mentioned HPMC solution again, stir evenly standby;
V, get the celphere coating, spray step IV gained solution is collected micropill to finishing;
VI, to pseudoephedrine hydrochloride micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again.
Promptly get pseudoephedrine hydrochloride medicine-feeding micropill, standby.
(3) dextromethorphan slow-release micro-pill
According to (2) technology, be equipped with the dextromethorphan slow-release micro-pill with legal system.
(4) Opadry is added in the pure water, and add pure water, stirred 1 hour to 100ml.
(5) get (2) (3) gained micropill and add an amount of magnesium stearate, mix homogeneously, tabletting, compressed together with (1) gained sheet again, the plain sheet that makes is put to coating pan, air blast is heated to about 50 ℃, at the uniform velocity spray into the coating solution coating, the limit sprays into the heating of coating solution snare drum wind, makes plain sheet temperature remain on 45-50 ℃, until evenly wrapping the thin film clothing, be drying to obtain coated tablet.
(6) the plain sheet that (1) is made is put to coating pan, and air blast is heated to about 50 ℃, at the uniform velocity sprays into the coating solution coating, and the limit sprays into the heating of coating solution snare drum wind, makes plain sheet temperature remain on 45-50 ℃, until evenly wrapping the thin film clothing, is drying to obtain.
(7) get (6), (2) (3) gained coated tablet, micropill fills in the hungry area softgel shell, promptly gets capsule.
The release characteristic of active component is as shown in table 5 in the gained different dosage form.
The release characteristic of active component in table 5 different dosage form
Embodiment 6
Prescription:
| Acetaminophen | 325g |
| Pseudoephedrine hydrochloride | 90g |
| Dextromethorphan hydrobromide | 30g |
| Celphere | 20g |
| Hydroxypropyl methylcellulose K4M | 57g |
| Hydroxypropyl methylcellulose E5 | 6g |
| Microcrystalline Cellulose | 42g |
| Pregelatinized Starch | 21g |
| Lactose | 70g |
| Sulisi aqueous dispersion (solid content 25%) | 80g |
| Light water dissolubility coating powder | 5g |
| Titanium dioxide | 5g |
| 10% 30 POVIDONE K 30 BP/USP 30Aqueous solution | In right amount |
| Water | In right amount |
| Magnesium stearate | 3g |
| Dehydrated alcohol | In right amount |
The coating prescription:
| Opadry | In right amount |
| Pure water | Add to 1000ml |
Preparation method:
(1) the plain sheet preparation of acetaminophen slow release
With recipe quantity hydroxypropyl methylcellulose K
4With the mixed powder of pregelatinized Starch, microcrystalline Cellulose with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate, promptly;
(2) pseudoephedrine hydrochloride slow release micropill
I, preparation 10%HPMC E5 aqueous solution, standby;
II, get the Sulisi aqueous dispersion and add water, shake up standby;
III, preparation contain the water solublity coating solution of water solublity coating powder 10%, titanium dioxide 1%;
IV, preparation 40% pseudoephedrine hydrochloride aqueous solution add above-mentioned HPMC solution again, stir evenly standby;
V, get the celphere coating, spray step IV gained solution is collected micropill to finishing;
VI, to pseudoephedrine hydrochloride micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again.
Promptly get pseudoephedrine hydrochloride medicine-feeding micropill, standby.
(3) dextromethorphan hydrobromide sustained-release tablets
It is evenly mixed to get the hydroxypropyl emthylcellulose-K4M, dextromethorphan hydrobromide, the lactose that claim recipe quantity successively, adds the magnesium stearate mix homogeneously of recipe quantity, surveys intermediate, tabletting.
(4) Opadry is added in the pure water, and add pure water, stirred 1 hour to 100ml.
(5) get (2) gained micropill and add an amount of magnesium stearate, mix homogeneously, tabletting with (1) and (3) tabletting, is put the plain sheet that makes to coating pan again, air blast is heated to about 50 ℃, at the uniform velocity spray into the coating solution coating, the limit sprays into the heating of coating solution snare drum wind, makes plain sheet temperature remain on 45-50 ℃, until evenly wrapping the thin film clothing, be drying to obtain.
(6) the plain sheet that (1) is made is put to coating pan, and air blast is heated to about 50 ℃, at the uniform velocity sprays into the coating solution coating, and the limit sprays into the heating of coating solution snare drum wind, makes plain sheet temperature remain on 45-50 ℃, until evenly wrapping the thin film clothing, is drying to obtain.
(7) get the plain sheet of (6), (2), (3) gained, coated tablet, micropill and fill in the hungry area softgel shell, promptly get capsule.
The release characteristic of active component is as shown in table 6 in the gained different dosage form.
The release characteristic of active component in table 6 different dosage form
Claims (1)
1. compound slow release preparation that is active component with acetaminophen, pseudoephedrine or its physiologically acceptable salt and dextromethorphan or its physiologically acceptable salt, it comprises a kind of delivery system, it is characterized in that: described delivery system is made up of the label that drug slow is discharged and/or ball core and coating, part or all is present in described active component in label and/or the ball core, the residual activity composition is present in the coating, wherein, the release characteristic of acetaminophen is: 2h:10-30%, 4h:20-50%, 8h: be not less than 50%; The release characteristic of pseudoephedrine or its physiologically acceptable salt is: 2h:42-85%, 4h:60-90%, 8h: be not less than 70%; The release characteristic of dextromethorphan or its physiologically acceptable salt is: 2h:30-60%, 4h:45-70%, 8h: be not less than 70%; The prescription and the preparation method of described compound slow release preparation are as follows:
By weight, 250 parts of acetaminophen, 90 parts of pseudoephedrine hydrochlorides, 30 parts of dextromethorphan hydrobromides, 6 parts of hydroxypropyl methylcellulose K4M, 60 parts of hydroxypropyl methylcellulose E5,36 parts of microcrystalline Cellulose, 30 parts of ethyl celluloses, magnesium stearate and 30 POVIDONE K 30 BP/USP
30Make in right amount, and by the following method:
(1) particulate preparation hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose E5 and microcrystalline Cellulose, cross 80 mesh sieves respectively, with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen and pseudoephedrine hydrochloride mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate, standby;
(2) preparation of coating solution is got dextromethorphan hydrobromide and is dissolved in the ethanol, adds ethyl cellulose, and mix homogeneously is standby;
(3) get (1) granule and carry out coating, obtain coated granule;
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet; Perhaps in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, promptly gets coated tablet; Perhaps get (3) gained particle packing in the hungry area softgel shell, promptly get capsule; Perhaps get (3) gained granule direct packaging, promptly get granule;
Perhaps:
By weight, 240 parts of acetaminophen, 100 parts of pseudoephedrine hydrochlorides, 20 parts of dextromethorphan hydrobromides, 6 parts of hydroxypropyl methylcellulose K4M, 75 parts of hydroxypropyl methylcellulose E5,45 parts of microcrystalline Cellulose, 70.5 parts of cellulose acetate, magnesium stearate and 30 POVIDONE K 30 BP/USP
30Make in right amount, and by the following method:
(1) particulate preparation hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose E5, microcrystalline Cellulose, cross 80 mesh sieves respectively, with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen and the 1/2 pseudoephedrine hydrochloride mix homogeneously of measuring, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate, standby;
(2) preparation of coating solution is got dextromethorphan hydrobromide and remaining pseudoephedrine hydrochloride is soluble in water, adds cellulose acetate, and mix homogeneously is standby;
(3) get (1) granule and carry out coating, obtain coated granule;
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet; Perhaps in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, promptly gets coated tablet; Perhaps get (3) gained particle packing in the hungry area softgel shell, promptly get capsule; Perhaps get (3) gained granule direct packaging, promptly get granule;
Perhaps:
By weight, 250 parts of acetaminophen, 90 parts of pseudoephedrine sulfates, 30 parts of dextromethorphan hydrobromides, 10 parts of hydroxypropyl methylcellulose K100M, 72 parts of hydroxyethyl-celluloses, 50 parts of microcrystalline Cellulose, 35 parts of cellulose diacetates, magnesium stearate and 30 POVIDONE K 30 BP/USP
30Make in right amount, and by the following method:
(1) particulate preparation hydroxypropyl methylcellulose K100M, hydroxyethyl-cellulose, microcrystalline Cellulose, cross 80 mesh sieves respectively, with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen, the dextromethorphan hydrobromide of 2/3 amount and the pseudoephedrine sulfate mix homogeneously of 4/9 amount, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 50 ℃ of dryings, 20 mesh sieve granulate, standby;
(2) preparation of coating solution is got the dextromethorphan hydrobromide of surplus and the pseudoephedrine sulfate of surplus is dissolved in the ethanol, adds cellulose diacetate, and mix homogeneously is standby;
(3) get (1) granule and carry out coating, obtain coated granule;
(4) in (3) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet; Perhaps in (1) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting is got (2) coating solution, is wrapped in outside the tablet, promptly gets coated tablet; Perhaps get (3) gained particle packing in the hungry area softgel shell, promptly get capsule; Perhaps get (3) gained granule direct packaging, promptly get granule;
Perhaps:
By weight, 325 parts of acetaminophen, 90 parts of pseudoephedrine hydrochlorides, 30 parts of dextromethorphan hydrobromides, 150 parts of celphere, 6 parts of hydroxypropyl methylcellulose E5,80 parts of the Sulisi aqueous dispersions of solid content 25%, 5 parts of water solublity coating powders, titanium dioxide part, 5 parts of stearic acid, 30 parts of Opadries, magnesium stearate and 30 POVIDONE K 30 BP/USP
30Make in right amount, and by the following method:
(1) acetaminophen slow-release micro-pill preparation
I, with an amount of 30 POVIDONE K 30 BP/USP
30Add an amount of dehydrated alcohol and be made into 5% (w/w) solution, standby;
II, stearic acid is added an amount of dehydrated alcohol be mixed with 5% (w/w) solution, standby;
III, get an amount of celphere and put in the coating pan;
IV, take by weighing the stearic acid ethanol solution for preparing and be sprayed on the celphere;
V, spray 30 POVIDONE K 30 BP/USP successively
30Ethanol solution, the hydrojet intermission also adds acetaminophen, treats that acetaminophen adheres to the ball wicking surface and repeats said process again, finishes until adding powder;
VI, take out and to make micropill in 35 ℃ of dryings 12 hours;
VII, sieve, promptly get the acetyl slow-release micro-pill with 14 mesh sieves and 20 orders, standby;
(2) pseudoephedrine hydrochloride slow release micropill
I, preparation 10% hydroxypropyl methylcellulose E5 aqueous solution, standby;
II, get the Sulisi aqueous dispersion and add water, shake up standby;
III, preparation contain the water solublity coating solution of water solublity coating powder 10%, titanium dioxide 1%;
IV, preparation 40% pseudoephedrine hydrochloride aqueous solution add above-mentioned hydroxypropyl methylcellulose E5 solution again, stir evenly standby;
V, get the celphere coating, spray step IV gained solution is collected micropill to finishing;
VI, to pseudoephedrine hydrochloride micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again, promptly get pseudoephedrine hydrochloride medicine-feeding micropill, standby;
(3) dextromethorphan slow-release micro-pill
According to (2) technology, be equipped with the dextromethorphan slow-release micro-pill with legal system;
(4) preparation of coating solution: Opadry is added in the pure water, and it is an amount of to add pure water, stirred 1 hour;
(5) get (1), (2) (3) micropill carries out coating with (4) coating solution, obtains coated granule;
(6) in (5) gained granule, add an amount of magnesium stearate, mix homogeneously, tabletting promptly gets tablet; Perhaps in (1), (2) (3) gained micropill, add an amount of magnesium stearate, mix homogeneously, tabletting is got (4) coating solution, is wrapped in outside the tablet, promptly gets coated tablet; Perhaps get (1), (2) (3) gained particle packing in the hungry area softgel shell, promptly get capsule; Perhaps get (1), (2) (3) gained granule direct packaging, promptly get granule;
Perhaps:
By weight, 325 parts of acetaminophen, 90 parts of pseudoephedrine hydrochlorides, 30 parts of dextromethorphan hydrobromides, 20 parts of celphere, 7 parts of hydroxypropyl methylcellulose K4M, 6 parts of hydroxypropyl methylcellulose E5,42 parts of microcrystalline Cellulose, 21 parts of pregelatinized Starch, 80 parts of the Sulisi aqueous dispersions of solid content 25%, 5 parts of light water dissolubility coating powders, 5 parts of titanium dioxide, 3 parts of magnesium stearate, Opadry and and 30 POVIDONE K 30 BP/USP
30Make in right amount, and by the following method:
(1) the plain sheet preparation of acetaminophen slow release
With hydroxypropyl methylcellulose K
4With the mixed powder of pregelatinized Starch, microcrystalline Cellulose with the abundant mixing of equivalent incremental method, again with equivalent incremental method and acetaminophen mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 60 ℃ of dryings, 20 mesh sieve granulate add the magnesium stearate mixing, tabletting, promptly;
(2) pseudoephedrine hydrochloride slow release micropill
I, preparation 10% hydroxypropyl methylcellulose E5 aqueous solution, standby;
II, get the Sulisi aqueous dispersion and add water, shake up standby;
III, preparation contain the water solublity coating solution of water solublity coating powder 10%, titanium dioxide 1%;
IV, preparation 40% pseudoephedrine hydrochloride aqueous solution add above-mentioned hydroxypropyl methylcellulose E5 solution again, stir evenly standby;
V, get the celphere coating, spray step IV gained solution is collected micropill to finishing;
VI, to pseudoephedrine hydrochloride micropill coating, spray into the Sulisi aqueous dispersion after, wrap the water solublity coating solution again, promptly get pseudoephedrine hydrochloride medicine-feeding micropill, standby;
(3) dextromethorphan slow-release micro-pill
According to (2) technology, be equipped with the dextromethorphan slow-release micro-pill with legal system;
(4) Opadry is added in the pure water, and it is an amount of to add pure water, stirred 1 hour;
(5) get (2) (3) gained micropill and add an amount of magnesium stearate, mix homogeneously, tabletting, compressed together with (1) gained sheet again, the plain sheet that makes is put to coating pan, air blast is heated to about 50 ℃, at the uniform velocity spray into (4) coating solution coating, the limit sprays into the heating of coating solution snare drum wind, makes plain sheet temperature remain on 45-50 ℃, until evenly wrapping the thin film clothing, be drying to obtain coated tablet; Perhaps the plain sheet that (1) is made is put to coating pan, air blast is heated to about 50 ℃, at the uniform velocity spray into (4) coating solution coating, the limit sprays into the heating of coating solution snare drum wind, make plain sheet temperature remain on 45-50 ℃, until evenly wrapping thin film clothing, drying, fill in the hungry area softgel shell with (2), (3) gained micropill again, promptly get capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101145746A CN101596158B (en) | 2008-06-04 | 2008-06-04 | Compound slow release preparation of acetyl aminophenol, pseudoephedrine and dextromethorphan |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101145746A CN101596158B (en) | 2008-06-04 | 2008-06-04 | Compound slow release preparation of acetyl aminophenol, pseudoephedrine and dextromethorphan |
Publications (2)
| Publication Number | Publication Date |
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| CN101596158A CN101596158A (en) | 2009-12-09 |
| CN101596158B true CN101596158B (en) | 2011-03-30 |
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| CN2008101145746A Expired - Fee Related CN101596158B (en) | 2008-06-04 | 2008-06-04 | Compound slow release preparation of acetyl aminophenol, pseudoephedrine and dextromethorphan |
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| 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 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475259A (en) * | 2003-05-16 | 2004-02-18 | 海口康力元制药有限公司 | Compound ganmaoling tablet (film coating tablet for treating common cold) and its manufacturing method |
| CN1543956A (en) * | 2003-11-24 | 2004-11-10 | 天津太平洋制药有限公司 | Compound paracetamol and chlorphenamine maleate slow releasing tablet and its preparation |
| CN1615866A (en) * | 2004-09-21 | 2005-05-18 | 石家庄制药集团欧意药业有限公司 | Anti-cold medicine soft capsule and its preparing method |
| CN1634061A (en) * | 2004-10-11 | 2005-07-06 | 贵阳云岩西创药物科技开发有限公司 | Pharmaceutical formulation of pseudoephenrine hydrochloride and its preparing process |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475259A (en) * | 2003-05-16 | 2004-02-18 | 海口康力元制药有限公司 | Compound ganmaoling tablet (film coating tablet for treating common cold) and its manufacturing method |
| CN1543956A (en) * | 2003-11-24 | 2004-11-10 | 天津太平洋制药有限公司 | Compound paracetamol and chlorphenamine maleate slow releasing tablet and its preparation |
| CN1615866A (en) * | 2004-09-21 | 2005-05-18 | 石家庄制药集团欧意药业有限公司 | Anti-cold medicine soft capsule and its preparing method |
| CN1634061A (en) * | 2004-10-11 | 2005-07-06 | 贵阳云岩西创药物科技开发有限公司 | Pharmaceutical formulation of pseudoephenrine hydrochloride and its preparing process |
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| 国家食品药品监督管理局.氨酚伪麻美芬片(Ⅲ).《中国药品标准XGB20072002》.2007, * |
| 闫立霞 等.缓释_控释片剂的发展概况.《天津药学》.1998,第10卷(第4期), |
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| CN101596158A (en) | 2009-12-09 |
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Address after: 100083 Haidian District, Xueyuan Road, No. 30, A building, room No. 15, room, room 15 Patentee after: COSCI MED-TECH Co.,Ltd. Address before: 100190, room 1410, satellite building, No. 63, Zhichun Road, Beijing, Haidian District Patentee before: COSCI MED-TECH Co.,Ltd. |
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