CN1830429A - Medicinal chewing tablet used for antipyretic analgesic and its preparation method - Google Patents

Abstract

A medicine in the form of chewing tablet for antipyresis and anodyne is prepared from ibuprofen through including it in cyclodextrin, mixing with filler and flavouring, granulating and die pressing.

Description

Be used for medicinal chewing tablet of antipyretic analgesic and preparation method thereof

Technical field

The present invention relates to a kind of medicinal chewing tablet that is used for antipyretic analgesic and preparation method thereof, the medicine that comprises is an ibuprofen, belongs to technical field of medicaments.

Background technology:

Ibuprofen is an antiinflammatory antipyretic analgesic series products, it is one of the most general non-steroidal anti-inflammatory drug of clinical use, chemistry Alpha-Methyl-4-(2-aminomethyl phenyl) phenylacetic acid by name, as prescribed and non prescribed medicine, be widely used for treating rheumatism or rheumatoid disease by numerous doctors, and multiple pain such as articular muscle is felt sorry, headache, dysmenorrhea; Ibuprofen is used for the adult already, and U.S. food in 1989 is ratified ibuprofen with Drug Administration and is used for the child as prescription drugs; The ibuprofen suspension of nineteen ninety-five commodity Motrin (Merrill Lynch) by name is used for 2～11 years old child by the FDA approval as the OTC medicine of antipyretic analgesic, and its drop in 1999 is used for the analgesic of child more than 6 months by the FDA approval for the OTC medicine.

In the existing at home Motrin, state-promulgated pharmacopoeia has been recorded ibuprofen syrup, ibuprofen tablet, ibuprofen oral liquid etc., but, the pungent taste that these dosage forms had can in throat, bring out a kind of bite the pain feel it is their common feature, make the patient be difficult to accept, especially children taking is difficult to accept especially; At present all oral formulations are not handled this composition, but directly being added relevant adjuvant, ibuprofen makes corresponding preparation, make the special acid that Motrin all contains ibuprofen like this, be prepared into buccal tablet or chewable tablet and just be difficult to allow especially child's acceptance of patient more.In addition, in prior art, the conventional method of preparation chewable tablet, mostly be to use correctivess such as sucrose, lactose, mannitol, xylitol, cyclamate, Aspartane separately, these correctivess can only be covered the abnormal flavour on ibuprofen surface, but still have comparatively serious acid taking the back root of the tongue, the idea that the patient is produced refuse to obey, and refusal is taken next time.Simultaneously; because the ibuprofen fusing point is lower; only be 74.5～77.5 ℃; the fusing and influence the tabletting quality easily when dry according to the conventional method wet granulation; though add some conventional filleies separately; as dextrin; Icing Sugar; soluble starch; lactose; mannitol etc., these filleies are granulated with ibuprofen separately or entirely after the powder mixes, are not easy tabletting; sticking usually takes place; its compression molding effect is all undesirable, and the easy moisture absorption of the slice, thin piece after the compacting makes the chewable tablet of molding softening; the tablet quality instability; for improving ibuprofen chewable tablet quality stability; mouldability, the abnormal flavour of ibuprofen chewable tablet particularly and degree of dissolving, the inventor has carried out research of the present invention.

Summary of the invention

The object of the present invention is to provide a kind of medicinal chewing tablet that is used for antipyretic analgesic and preparation method thereof, the medicine that comprises is an ibuprofen, chemistry Alpha-Methyl-4-(2-aminomethyl phenyl) phenylacetic acid by name; The present invention adopts coprecipitation with the ibuprofen enclose ibuprofen and cyclodextrin, gets the enclose powder, and the enclose powder adds suitable adjuvant, makes chewable tablet.Having solved ibuprofen has acid, patient and is reluctant oral problem; The enclose powder directly is prepared into chewable tablet or buccal tablet, good, the taking convenience of mouthfeel not only, and owing to improved the dissolubility of ibuprofen, enable to reach rapidly the effect of antipyretic analgesic, improved chewable tablet quality stability, mouldability, medicine is by chewing or containing, its effective ingredient through port transmucosal or hypoglossis mucous membrane absorb rapidly, absorb soon, the bioavailability height is to solve the problem that prior art exists.

The medicine ibuprofen chewable tablet that the present invention is used for antipyretic analgesic is to constitute like this: it is composed of the following components: weight portion is 10～100 parts ibuprofen, the cyclodextrin that weight portion is 10～500 parts, the filler that weight portion is 20～200 parts, the correctives that weight portion is 5～100 parts, the fluidizer that weight portion is 1～20 part, the flavoring agent that weight portion is 0～100 part, the binding agent that weight portion is 5～100 parts, the food coloring that weight portion is 0～5 part.

Described cyclodextrin is used for enclose medicine ibuprofen to cover the acid of ibuprofen, can select following a kind of or two or more mixture arbitrarily, comprise: alpha-cyclodextrin, beta-schardinger dextrin-, gamma-cyclodextrin, hydroxypropyl-alpha-cyclodextrin, HP-, hydroxypropyl-gamma-cyclodextrin, methyl-beta-schardinger dextrin-, carboxymethyl-beta-cyclodextrin, one chlorotriazine-beta-schardinger dextrin-.

Described filler is as diluent, can select following a kind of or two or more mixture arbitrarily, comprising: lactose, dextrin, sucrose, mannitol, xylitol, fructose, glucose, soluble starch, Mel, microcrystalline Cellulose.

Described correctives is used for correcting the mouthfeel of medicine ibuprofen chewable tablet, can select following a kind of or two or more mixture arbitrarily, comprising: cyclamate, Aspartane, stevioside, glycyrrhizin, chocolate, organic acid, acylate.

Flowability when described fluidizer is used for increasing ibuprofen chewable tablet tabletting, can select following a kind of or two or more mixture arbitrarily, comprising: fluidizer comprises: magnesium stearate, Pulvis Talci, micropowder silica gel, Polyethylene Glycol, microcrystalline Cellulose.

Described flavoring agent is used for covering the bad stink of ibuprofen chewable tablet, can select following a kind of or two or more mixture arbitrarily, and comprising: human body can be accepted the powdered flavor of taste.

Described food coloring is used for increasing the allure that ibuprofen chewable tablet appearance luster is taken medicine with raising, can select following a kind of or two or more mixture arbitrarily, comprising: the pigment of acceptable color on the human body sense organ.

Described binding agent is used for increasing bonding force between the medicine, can select following a kind of or two or more mixture arbitrarily, comprise: the pressed powder of gelatin, Resina persicae, tragakanta, xanthan gum, propolis, carrageenan, guar gum, agar, arabic gum, sodium alginate, pectin, Semen Lini glue, the polysaccharide that condenses, pulullan, gellan gum, propylene glycol alginate, locust bean gum and Konjac glucomannan or solution and ethanol, polyglycol solution, polyvinylpyrrolidonesolution solution, cellulose derivative alcoholic solution.

The described preferred ingredient that is used for analgesic medicine ibuprofen chewable tablet component of ending prepares according to following prescription: ibuprofen 10～100g, betacyclodextrin 10～500g, mannitol 10～100g, lactose 10～100g, citric acid 2～50g, Aspartane 1～20g, potassium hydrogen tartrate 1～20g, cyclamate 1～10g, magnesium stearate 1～20g, orange flavor essence 1～100g, xanthan gum 10～50g, polyvinylpyrrolidone alcoholic solution 2～50g, sunset yellow 0.025～2.5g, carmine 0.025～2.5g.

The described best composition that is used for the medicine ibuprofen chewable tablet component of antipyretic analgesic prepares according to following prescription: ibuprofen 50g, betacyclodextrin 125g, mannitol 150g, lactose 80, citric acid 12g, Aspartane 7.2g, potassium hydrogen tartrate 24g, xanthan gum 12g, cyclamate 5g, orange flavor essence 1.8g, sunset yellow 0.12g, carmine 0.12g, magnesium stearate 1.2g, 15% polyvinylpyrrolidone, 80% ethanol liquid 20g.

The preparation method of ibuprofen chewable tablet is to be prepared according to following steps:

A, except that ibuprofen, cyclodextrin, supplementary material is pulverized and to be crossed 80 mesh sieves respectively;

B, ibuprofen add an amount of ethanol tepor makes its dissolving, and cyclodextrin adds water and make saturated solution in water bath with thermostatic control, under agitation slowly adds the ibuprofen alcoholic solution in the cyclodextrin solution, constant temperature stirred 0.5～2 hour, stop heating, continue to be stirred to room temperature, get white suspension, cold preservation, sucking filtration, precipitate cleans twice with ethanol, drying, pulverize, standby;

C, mix homogeneously such as filler, correctivess;

D, the method that food coloring is progressively increased by equivalent add in the mixed powder of gained among the above-mentioned C, behind the mix homogeneously, add the ibuprofen-cyclodextrin inclusion compound precipitate of gained among the B again, stir, add binding agent powder and/or binder solution system soft material then, system wet granular, cold drying;

E, with the dried particles granulate that sieves, add flavoring agent, fluidizer mix homogeneously, tabletting, promptly.

Be used for the medicine ibuprofen chewable tablet of antipyretic analgesic concrete preparation method, be to be prepared according to following steps:

A, mannitol, lactose, citric acid, potassium hydrogen tartrate, cyclamate are pulverized earlier, crossed 80 mesh sieves, standby;

B, get the recipe quantity ibuprofen, add an amount of ethanol tepor and make its dissolving, other takes by weighing the recipe quantity betacyclodextrin, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the betacyclodextrin solution, constant temperature stirred 1 hour, stopped heating, continued to be stirred to room temperature, get white suspension, cold preservation 12 hours, sucking filtration, precipitate cleans twice with ethanol, aeration-drying below 60 ℃ is pulverized, and is standby;

C, take by weighing mannitol, lactose, citric acid, potassium hydrogen tartrate, cyclamate, Aspartane by recipe quantity and mix the back evenly;

D, take by weighing mouth fall Huang, carmine by recipe quantity, the method of progressively increasing by equivalent adds in the mixed powder of gained among the above-mentioned C, behind the mix homogeneously, ibuprofen-betacyclodextrin enclose the precipitate that adds gained among the B again, stir, it is even to add the xanthan gum powder mixes then, the 80% ethanol liquid system soft material of reuse 15%PVP, cross 20 mesh sieves and make wet granular, 50 ℃ of oven dry;

E, will dry granule and cross 20 mesh sieve granulate, add orange flavor essence, the magnesium stearate mixing of recipe quantity, tabletting, promptly.

The present invention has changed in the prior art and the ibuprofen raw material directly have been added the method for making preparation behind the adjuvant mix homogeneously, on the basis that does not change ibuprofen composition and curative effect, ibuprofen is wrapped up with cyclodextrin, make ibuprofen and cyclodextrin form the clathrate of molecule capsula interna, covered the acid of ibuprofen, add the filler of forming ibuprofen chewable tablet component with the ibuprofen cyclodextrin clathrate then, correctives, the food coloring mix homogeneously, with binding agent and/or binder solution system soft material, granulate, add flavoring agent at last, the fluidizer mix homogeneously, tabletting, promptly; Solved because of adding the problem that the adjuvant direct compression has acid with ibuprofen, also solved and be used alone adjuvant sticking takes place easily, the all undesirable problem of tablet molding effect, the easy moisture absorption of slice, thin piece after having avoided compacting in blocks, make the chewable tablet of molding softening, the tablet quality wild effect, ibuprofen chewable tablet quality stability, mouldability have been improved, preparation of the present invention, through behind the cyclodextrin inclusion compound, improved the dissolubility of ibuprofen, by chewing or containing, the abundant blood capillary in drug port transmucosal and Sublingual absorbs directly into blood, onset rapidly; Avoid first pass effect of hepar simultaneously, improved the utilization rate of medicine.

Therefore, compared with prior art, the present invention has steady quality, mouthfeel is good, dissolubility improves, it is fast to absorb, bioavailability height and the advantage of being convenient to take.

Cyclodextrin of the present invention, filler, correctives, fluidizer, flavoring agent, binding agent, pigment are the medicinal and/or edible pigments of state's laws permission to use, edible safety.

The method that prior art or conventional method are meant is that disclosed technology, national standard state clearly, the professional and technical personnel in the pharmacy textbook or this field can consult, implement.

For confirming the seal effect of the present invention to cyclodextrin parcel ibuprofen, the applicant adopts L ₉(3 ³) orthogonal experiment, studied the technology of beta-cyclodextrin inclusion compound ibuprofen.By the investigation to clathrate content of dispersion and two indexs of productive rate, optimizing clathrate process is A ₂B ₂C ₃, promptly with the beta-cyclodextrin inclusion compound of 1: 1 gram-molecular weight of ibuprofen, the enclose temperature is 80 ℃, constant temperature enclose 1h continues enclose then to room temperature, and verifies by the optimised process that experiment obtains.Test as follows:

The enclose L of beta-cyclodextrin inclusion compound Bu Luoqie ₉(3 ³) orthogonal test:

1 material and instrument:

1.1 material: medical material meets " regulation under 2005 editions one each medicine item of Chinese pharmacopoeia through evaluation; Ibuprofen, Shandong Xinhua Pharmaceutical Factory, purity＞98%; Beta-schardinger dextrin-, Suzhou Gourmet Powder Factory produces, purity＞98%; Reagent is analytical pure.

1.2 equipment and instrument: electronic thermostatic water-bath, Bei Jingjing are defended scientific instrument factory; SXJQ-1 type motor stirrer; Scout 11 electronic balances, Ao Haosi International Trading Company Ltd; 101-2 type drying baker, Shanghai City experimental apparatus head factory.

2 methods and result:

2.1 clathrate preparation technology's selection

Adopt the orthonormal design of experiments method, press table 1 and select experiment condition, adopt saturated water solution method-electronic stirring method to prepare clathrate, learn through test, mole ratio is bigger to inclusion rate, yield influence, so give ibuprofen: the beta-schardinger dextrin-mole ratio is added one group of level, so that more fully investigate.Adopt part additional method experiment arrangement scheme, with actual content and productive rate is that index is carried out overall merit, the gained data as calculated, the best preparation process condition that draws ibuprofen-Benexate Hydrochloride is as follows: take by weighing ibuprofen and add an amount of ethanol tepor and make its dissolving, other takes by weighing the beta-schardinger dextrin-of 1: 1 gram-molecular weight of ibuprofen, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the betacyclodextrin solution, stirred 1 hour with 2000rpm constant temperature with motor stirrer, stop heating, continue to be stirred to room temperature, get white suspension, cold preservation 12 hours, sucking filtration, 0.45 the filtering with microporous membrane of μ m, the precipitate cold drying is weighed and calculated yield, pulverized 80 mesh sieves then, be stored in the exsiccator standby, according to " 2005 editions two the 95th page of ibuprofen assay items of Chinese pharmacopoeia are measured down ibuprofen content, the results are shown in Table 2.

The factor of table 1 orthogonal test and level

Level	Ibuprofen: beta-schardinger dextrin-(mole ratio)	Mixing time (h)	Preparation temperature (℃)
				1	1∶0.5	0.5	40
2	1∶1.0	1.0	60
				3	1∶1.5	1.5	80

Table 2 ibuprofen-Benexate Hydrochloride content and productive rate

Clathrate sample weighting amount (g)	Clathrate contains ibuprofen amount (%)	Clathrate recovery rate (%)
			11.75	12.33	80.08
11.71	11.66	80.07
			12.03	11.98	79.33

The quality examination of 3 clathrates

3.1 microexamination

Beta-schardinger dextrin-is pressed this preparation method, preparation does not contain the blank clathrate of ibuprofen, this product and pastille clathrate are respectively taken a morsel, place respectively under the biological microscope and observe: blank clathrate is the plate crystal of rule, and the pastille clathrate is the irregular block sprills.

3.2 taste test

With beta-schardinger dextrin-, ibuprofen and the ibuprofen-Benexate Hydrochloride packing of not marking respectively, there are 20 people (age 18-30 year) to participate in taste test, and the record result, clathrate does not have acid and slightly pleasantly sweet fully as a result.

3.3 the stability of clathrate

Getting ibuprofen, ibuprofen-Benexate Hydrochloride powder places respectively in 40 ℃, the climatic chamber of relative humidity 75% and placed 3 months, sampling and measuring was 1 time in every month, ibuprofen and ibuprofen-Benexate Hydrochloride downgrade that the result placed 3 months are respectively 1.06% and 1.26%, show that ibuprofen-Benexate Hydrochloride is stable before the deadline.

4 discuss

4.1 optimization of preparation

Adopting orthogonal design that the preparation technology of clathrate is optimized, is index evaluation with the yield of clathrate, actual inclusion rate, and the result shows that ibuprofen-Benexate Hydrochloride is in host and guest's molecule ratio of 1: 1 mole ratio, and is better in 80 ℃ of electronic stirring 1h.

4.2 the coverage effect of clathrate

Studies show that, adopt the clathrate technology can cover acid fully, and beta-schardinger dextrin-also can improve stability, increase dissolubility behind enclose.And in mimic artificial saliva, the rate of release of clathrate is higher than ibuprofen, this is because dissolubility is less in water, and the dissolubility of clathrate is about 10 times of ibuprofen, ibuprofen-Benexate Hydrochloride just reaches stable emission levels in 10min, dissolubility is greater than ibuprofen in water.Therefore, can utilize the present invention, preparation ibuprofen chewable tablet reaches refrigeration function rapidly provides foundation.

In order to confirm that the present invention adopts the mixed accessories of mannitol and lactose to prepare mouthfeel, mouldability, the stability of ibuprofen chewable tablet, the applicant has carried out related experiment, and its experimental result is as follows:

1, sample treatment

Sample 1 is got ibuprofen and is ground into fine powder, adds the sucrose of 300% times of amount of ibuprofen, and mix homogeneously is granulated, and adds the magnesium stearate of making 0.5% times of amount of total amount behind the granule at last, mix homogeneously, compacting in flakes, promptly.

Sample 2 is got ibuprofen and is ground into fine powder, adds the mannitol of 300% times of amount of ibuprofen and the cyclamate of 20% times of amount of ibuprofen, and mix homogeneously is granulated, and adds the magnesium stearate of making 0.5% times of amount of total amount behind the granule at last, mix homogeneously, compacting in flakes, promptly.

Sample 3 is got ibuprofen and is ground into fine powder, adds the lactose of 300% times of amount of ibuprofen and the cyclamate of 20% times of amount of ibuprofen, and mix homogeneously is granulated, and adds the magnesium stearate of making 0.5% times of amount of total amount behind the granule at last, mix homogeneously, compacting in flakes, promptly.

Sample 4 is got ibuprofen and is added an amount of ethanol tepor and make its dissolving, and other takes by weighing the betacyclodextrin of 1: 1 gram-molecular weight of ibuprofen, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the betacyclodextrin solution, constant temperature stirred 1 hour, stopped heating, continued to be stirred to room temperature, got white suspension, cold preservation 12 hours, and sucking filtration, precipitate is standby; Recipe quantity mannitol, carboxymethyl starch sodium, citric acid, potassium hydrogen tartrate, cyclamate are pulverized earlier, crossed 80 mesh sieves, standby; Take by weighing mannitol, citric acid, potassium hydrogen tartrate, cyclamate, Aspartane mixing back evenly by recipe quantity; Take by weighing sunset yellow, carmine by recipe quantity again, the method of progressively increasing by equivalent adds in the above-mentioned mixed powder, behind the mix homogeneously, add ibuprofen-betacyclodextrin enclose precipitate again, stir, add the xanthan gum mix homogeneously then, the 80% ethanol liquid system soft material of reuse 15%PVP, cross 20 mesh sieves and make wet granular, 50 ℃ of oven dry; To dry granule and cross 20 mesh sieve granulate, add orange flavor essence, the magnesium stearate mixing of recipe quantity, tabletting, promptly.

2, mouthfeel inspection

Adopt double-blind method with the medicine packing of not marking respectively the ibuprofen chewable tablet of sample 1,2,3,4, preferred normal 10 people of the sense of taste (age 18-30 year) participate in taste test, and write down the result, the results are shown in Table 3.

The different sample mouthfeels of table 3 ibuprofen chewable tablet are checked

Sample	1	2	3	4
					Mouthfeel	Sweet and pungent	Pungent	Pungent	Dissolve all sweet no pungent

As can be seen from Table 2, owing to the relation of sucrose, sensation is sweet then pungent pungent taste earlier after sample 1 was taken, and sample 2,3 is taken aftersensation pungent pungent taste, and sample 4 is not felt acid from taking the back up to dissolving, and pleasantly sweet; Sample 4 is exactly the chewable tablet according to method preparation of the present invention.

3, mouldability

Test tabletting, outward appearance, color and luster according to the pertinent regulations under 2005 editions one appendix ID tablet of the Chinese Pharmacopoeia item, the results are shown in Table 4.

The different sample molding of table 4 ibuprofen chewable tablet situation

Sample	1	2	3	4
					Tabletting	Sticking very	The sticking phenomenon is arranged	Rare sticking phenomenon	No sticking phenomenon
Outward appearance	Rough surface	There is pit on the surface	Smooth surface	Smooth surface, light
					Color and luster	Skin dark stain is arranged	Evenly	Evenly	Evenly

As can be seen from Table 3, sample 1 when tabletting because sticking, the time compression molding after slice, thin piece rough surface occurs and have some skin dark stains to exist; Sample 2 compares with sample 1, and the sticking situation take a favorable turn during tabletting, but still has sticking and surperficial pitted situation; Sample 3 samples 2 are that idol has sticking situation, smooth surface during tabletting relatively; There is not any sticking phenomenon during sample 4 tablettings, slice, thin piece smooth surface, light, color and luster is even, and sample 4 promptly is the chewable tablet according to method preparation of the present invention.

4, stability

Test sample 10g puts in the constant-temperature enclosed container, places 10 days under respectively at relative humidity 90 ± 5% conditions at 25 ℃, and in the 5th day and sampling in the 10th day, accurately test sample weight before and after the weighing test with investigation test sample moisture pick-up properties, the results are shown in Table 5.

The different sample hygroscopicity of table 5 are investigated

Sample	The 0th day	The 5th day		The 10th day
						Before the test heavy (g)	Test back heavy (g)	Weightening finish (%)	Test back heavy (g)	Weightening finish (%)
	1	10.1672	10.8084	6.31	11.0444						9.31
2						10.1039	10.7260	6.16	10.9637	8.51
	3	10.2016	10.7388	5.27	11.0106						7.93
4						10.0091	10.0477	4.67	10.5526	5.43
	5	10.0112	10.3010	2.89	10.4697						4.58
6						10.0059	10.1004	0.94	10.1400	1.34

As can be seen from Table 5, sample 1,2 its weightening finish when the 5th day detects surpasses 5%, though sample 3 did not surpass 5% at the 5th day, near 5%, and at the 10th day also all above 5%; Have only sample 4 not surpass 5% its weightening finish in the 10th day.Show that thus sample 1,2,3 has higher hygroscopicity, sample 4 has stronger humidity-proof ability, can keep particulate drying property in a long time.

Data analysis from three experiments, the mouthfeel of sample 4, mouldability and humidity-proof ability all are better than other sample, and sample 4 is the chewable tablet according to the inventive method preparation, illustrate that the present invention can effectively solve the molding of the pungent pungent taste of ibuprofen, chewable tablet and the problem of high moisture absorption, the ibuprofen chewable tablet of making can be guaranteed the stability of product quality.

The specific embodiment:

Embodiments of the invention 1:

One, prescription: ibuprofen 50g

Betacyclodextrin 125g

Mannitol 150g

Lactose 30

Citric acid 12g

Aspartane 7.2g

Potassium hydrogen tartrate 24g

Xanthan gum 12g

Cyclamate 5g

Orange flavor essence 1.8g

Sunset yellow 0.12g

Carmine 0.12g

Magnesium stearate 1.2g

10% polyvinylpyrrolidone, 80% ethanol liquid 20g.

Two, method for making:

A, mannitol, lactose, citric acid, potassium hydrogen tartrate, cyclamate are pulverized earlier, crossed 80 mesh sieves, standby;

B, get the recipe quantity ibuprofen, add an amount of ethanol tepor and make its dissolving, other takes by weighing the recipe quantity betacyclodextrin, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the betacyclodextrin solution, constant temperature stirred 1 hour, stopped heating, continued to be stirred to room temperature, get white suspension, cold preservation 12 hours, sucking filtration, precipitate cleans twice with ethanol, aeration-drying below 60 ℃ is pulverized, and is standby;

C, take by weighing mannitol, lactose, citric acid, potassium hydrogen tartrate, cyclamate, Aspartane by recipe quantity and mix the back evenly;

D, take by weighing mouth fall Huang, carmine by recipe quantity, the method of progressively increasing by equivalent adds in the mixed powder of gained among the above-mentioned C, behind the mix homogeneously, the ibuprofen betacyclodextrin enclose precipitate that adds gained among the B again, stir, it is even to add the xanthan gum powder mixes then, the 80% ethanol liquid system soft material of reuse 15%PVP, cross 20 mesh sieves and make wet granular, 50 ℃ of oven dry;

E, will dry granule and cross 20 mesh sieve granulate, and add orange flavor essence, the magnesium stearate mixing of recipe quantity, tabletting is made 1000, every 0.425g, promptly.

Embodiments of the invention 2:

One, prescription: ibuprofen 10g

Betacyclodextrin 10g

Mannitol 10g

Lactose 10g

Citric acid 2g

Stevioside 1g

Potassium hydrogen tartrate 1g

Propolis 10g

Cyclamate 1g

The smart 1g of fragrant burnt odor

Lemon yellow 0.05g

Micropowder silica gel 1g

20% ethyl cellulose ethanol liquid 20g.

Two, method for making:

1, mannitol, lactose, citric acid, potassium hydrogen tartrate, cyclamate are pulverized earlier, crossed 80 mesh sieves, standby;

2, get the recipe quantity ibuprofen, add an amount of ethanol tepor and make its dissolving, other takes by weighing the recipe quantity betacyclodextrin, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the betacyclodextrin solution, constant temperature stirred 1 hour, stopped heating, continued to be stirred to room temperature, get white suspension, cold preservation 12 hours, sucking filtration, precipitate cleans twice with ethanol, aeration-drying below 60 ℃ is pulverized, and is standby;

3, take by weighing mannitol, lactose, citric acid, potassium hydrogen tartrate, cyclamate, stevioside mixing back evenly by recipe quantity;

4, taking by weighing the method that lemon yellow progressively increases by equivalent by recipe quantity adds in the mixed powder of gained among the above-mentioned C, behind the mix homogeneously, the ibuprofen betacyclodextrin enclose precipitate that adds gained among the B again, stir, add propolis powder mix homogeneously then, reuse 20% ethyl cellulose ethanol liquid system soft material is crossed 20 mesh sieves and is made wet granular, 50 ℃ of oven dry;

5, will dry granule and cross 20 mesh sieve granulate, and add fragrant burnt odor essence, the micropowder silica gel mixing of recipe quantity, tabletting is made 1000, every 0.06g, promptly.

Embodiments of the invention 3:

One, prescription: ibuprofen 100g

Gamma-cyclodextrin 500g

Mannitol 100g

Lactose 100g

Malic acid 50g

Glycyrrhizin 20g

Potassium hydrogen tartrate 20g

Resina persicae 50g

Cyclamate 10g

Apple essence 10g

Maize 1.5g

Apple green 3.5g

Pulvis Talci 20g

10% Polyethylene Glycol alcoholic solution 100g.

Two, method for making:

1, mannitol, lactose, malic acid, potassium hydrogen tartrate, cyclamate are pulverized earlier, crossed 80 mesh sieves, standby;

2, get the recipe quantity ibuprofen, add an amount of ethanol tepor and make its dissolving, other takes by weighing the recipe quantity gamma-cyclodextrin, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the gamma-cyclodextrin solution, constant temperature stirred 1 hour, stopped heating, continued to be stirred to room temperature, get white suspension, cold preservation 12 hours, sucking filtration, precipitate cleans twice with ethanol, aeration-drying below 60 ℃ is pulverized, and is standby;

3, take by weighing mannitol, lactose, malic acid, potassium hydrogen tartrate, cyclamate, glycyrrhizin mixing back evenly by recipe quantity;

4, take by weighing maize, apple green by recipe quantity, the method of progressively increasing by equivalent adds in the mixed powder of gained among the above-mentioned C, behind the mix homogeneously, ibuprofen-gamma-cyclodextrin enclose the precipitate that adds gained among the B again, stir, add Resina persicae powder mix homogeneously then, reuse 10% Polyethylene Glycol alcoholic solution system soft material, cross 20 mesh sieves and make wet granular, 50 ℃ of oven dry;

5, will dry granule and cross 20 mesh sieve granulate, and add apple essence, the Pulvis Talci mixing of recipe quantity, tabletting is made 1000, every 1.00g, promptly.

Embodiments of the invention 4:

One, prescription: ibuprofen 50g

Alpha-cyclodextrin 250g

Xylitol 150g

Sucrose 80

Gallic acid 12g

Stevioside 7.2g

Potassium hydrogen phosphate 24g

Arabic gum 30g

Cyclamate 5g

Chocolate powder 50g

Microcrystalline Cellulose 1.8g

60% ethanol liquid 30g.

Two, method for making:

A, xylitol, sucrose, gallic acid, potassium hydrogen phosphate, stevioside, cyclamate are pulverized earlier, crossed 80 mesh sieves, standby;

B, get the recipe quantity ibuprofen, add an amount of ethanol tepor and make its dissolving, other takes by weighing the recipe quantity alpha-cyclodextrin, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the alpha-cyclodextrin solution, constant temperature stirred 1 hour, stopped heating, continued to be stirred to room temperature, get white suspension, cold preservation 12 hours, sucking filtration, precipitate cleans twice with ethanol, aeration-drying below 60 ℃ is pulverized, and is standby;

C, take by weighing xylitol, sucrose, gallic acid, potassium hydrogen phosphate, stevioside, cyclamate, chocolate powder mix homogeneously by recipe quantity, ibuprofen-alpha-cyclodextrin enclose the precipitate that adds gained among the B again, stir, add arabic gum powder mix homogeneously then, reuse 60% ethanol liquid system soft material, cross 20 mesh sieves and make wet granular, 50 ℃ of oven dry;

E, will dry granule and cross 20 mesh sieve granulate, add the microcrystalline Cellulose mixing of recipe quantity, tabletting, 1000, every 0.66g, promptly.

Embodiments of the invention 5:

One, prescription: ibuprofen 50g

HP-250g

Mannitol 150g

Lactose 80

Tartaric acid 12g

Aspartane 7.2g

Potassium hydrogen tartrate 24g

Sodium alginate 12g

Cyclamate 5g

Grape essence 1.8g

Light blue 0.12g

Amaranth 0.36g

Magnesium stearate 1.2g

10% polyvinylpyrrolidone, 80% alcoholic solution 20g.

One, method for making:

A, mannitol, lactose, tartaric acid, potassium hydrogen tartrate, cyclamate are pulverized earlier, crossed 80 mesh sieves, standby;

B, get the recipe quantity ibuprofen, add an amount of ethanol tepor and make its dissolving, other takes by weighing the recipe quantity HP-, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the HP-solution, constant temperature stirred 1 hour, stopped heating, continued to be stirred to room temperature, get white suspension, cold preservation 12 hours, sucking filtration, precipitate cleans twice with ethanol, aeration-drying below 60 ℃ is pulverized, and is standby;

C, take by weighing mannitol, lactose, tartaric acid, potassium hydrogen tartrate, cyclamate, Aspartane by recipe quantity and mix the back evenly;

D, take by weighing the method that light blue, amaranth progressively increase by equivalent by recipe quantity and add in the mixed powder of gained among the above-mentioned C, behind the mix homogeneously, ibuprofen hydroxyl-propyl group-beta-cyclodextrin inclusion compound the precipitate that adds gained among the B again, stir, add the sodium alginate powder mix homogeneously then, reuse 10% polyvinylpyrrolidone 80% alcoholic solution system soft material is crossed 20 mesh sieves and is made wet granular, 50 ℃ of oven dry;

E, will dry granule and cross 20 mesh sieve granulate, and add grape essence, the magnesium stearate mixing of recipe quantity, tabletting is made 1000, every 0.6g, promptly.

Claims (12)

1, be used for the medicinal chewing tablet of antipyretic analgesic, it is characterized in that: it is composed of the following components: weight portion is 10～100 parts ibuprofen, the cyclodextrin that weight portion is 10～500 parts, the filler that weight portion is 20～200 parts, the correctives that weight portion is 5～100 parts, the fluidizer that weight portion is 1～20 part, the flavoring agent that weight portion is 0～100 part, the binding agent that weight portion is 5～100 parts, the pigment that weight portion is 0～5 part.

2, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 1, it is characterized in that described cyclodextrin comprises: alpha-cyclodextrin, beta-schardinger dextrin-, gamma-cyclodextrin, hydroxypropyl-alpha-cyclodextrin, HP-, hydroxypropyl-gamma-cyclodextrin, methyl-beta-schardinger dextrin-, a kind of in carboxymethyl-beta-cyclodextrin, the one chlorotriazine-beta-schardinger dextrin-or two or more mixture arbitrarily.

3, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 1 is characterized in that described filler comprises: two or more mixture of any in lactose, dextrin, sucrose, mannitol, xylitol, soluble starch, fructose, glucose, microcrystalline Cellulose, the Mel or they.

4, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 1 is characterized in that described correctives comprises: two or more mixture of any in cyclamate, Aspartane, stevioside, glycyrrhizin, chocolate, organic acid, the acylate or they.

5, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 1 is characterized in that described fluidizer comprises: two or more mixture of any in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol or they.

6, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 1 is characterized in that described flavoring agent is the powdered flavor that human body can be accepted taste.

7, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 1 is characterized in that described pigment is the pigment of acceptable color on the human body sense organ.

8, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 1 is characterized in that described binding agent comprises: gelatin, Resina persicae, the tragakanta, xanthan gum, propolis, carrageenan, guar gum, agar, arabic gum, sodium alginate, pectin, Semen Lini glue, polysaccharide condenses, pulullan, gellan gum, propylene glycol alginate, the pressed powder of locust bean gum and Konjac glucomannan or solution and ethanol, the Polyethylene Glycol alcoholic solution, polyvinylpyrrolidine alkane ketone alcoholic solution, two or more mixture of any in the cellulose derivative alcoholic solution or they.

9, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 1, it is characterized in that: it is made up of following prescription: ibuprofen 10～100g, betacyclodextrin 10～500g, mannitol 10～100g, lactose 10～100g, citric acid 2～50g, Aspartane 1～20g, potassium hydrogen tartrate 1～20g, cyclamate 1～10g, magnesium stearate 1～20g, orange flavor essence 1～10g, xanthan gum 10～50g, polyvinylpyrrolidone alcoholic solution 2～100g, sunset yellow 0.025～2.5g, carmine 0.025～2.5g.

10, the medicinal chewing tablet that is used for antipyretic analgesic according to claim 9, it is characterized in that: it is made up of following prescription: ibuprofen 50g, betacyclodextrin 125g, mannitol 150g, lactose 30, citric acid 12g, Aspartane 7.2g, potassium hydrogen tartrate 24g, xanthan gum 12g, cyclamate 5g, orange flavor essence 1.8g, sunset yellow 0.12g, carmine 0.12g, magnesium stearate 1.2g, 10% polyvinylpyrrolidone, 80% ethanol liquid 20g.

11, a kind of preparation method that is used for the medicinal chewing tablet of antipyretic analgesic as claimed in claim 1 is characterized in that: be prepared according to following steps:

A, except that ibuprofen, cyclodextrin, all the other supplementary materials are pulverized and are crossed 80 mesh sieves respectively;

B, ibuprofen add an amount of ethanol tepor makes its dissolving, and cyclodextrin adds water and make saturated solution in water bath with thermostatic control, under agitation slowly adds the ibuprofen alcoholic solution in the cyclodextrin solution, constant temperature stirred 0.5～2 hour, stop heating, continue to be stirred to room temperature, get white suspension, cold preservation, sucking filtration, precipitate cleans twice with ethanol, drying, pulverize, standby;

C, mix homogeneously such as filler, correctivess;

D, the method that food coloring is progressively increased by equivalent add in the mixed powder of gained among the above-mentioned C, behind the mix homogeneously, add the ibuprofen-cyclodextrin inclusion compound precipitate of gained among the B again, stir, add binding agent powder and/or binder solution system soft material then, system wet granular, cold drying;

E, with the dried particles granulate that sieves, add flavoring agent, fluidizer mix homogeneously, tabletting, promptly.

12, a kind of preparation method that is used for the medicinal chewing tablet of antipyretic analgesic as claimed in claim 11 is characterized in that: be prepared according to following steps:

A, mannitol, lactose, citric acid, potassium hydrogen tartrate, cyclamate are pulverized earlier, crossed 80 mesh sieves, standby;

B, get the recipe quantity ibuprofen, add an amount of ethanol tepor and make its dissolving, other takes by weighing the recipe quantity betacyclodextrin, adds water and make saturated solution in 80 ℃ of waters bath with thermostatic control.Under agitation the ibuprofen alcoholic solution is slowly added in the betacyclodextrin solution, constant temperature stirred 1 hour, stopped heating, continued to be stirred to room temperature, get white suspension, cold preservation 12 hours, sucking filtration, precipitate cleans twice with ethanol, aeration-drying below 60 ℃ is pulverized, and is standby;

C, take by weighing mannitol, lactose, citric acid, potassium hydrogen tartrate, cyclamate, Aspartane by recipe quantity and mix the back evenly;

D, take by weighing sunset yellow, carmine by recipe quantity, the method of progressively increasing by equivalent adds in the mixed powder of gained among the above-mentioned C, behind the mix homogeneously, ibuprofen-betacyclodextrin enclose the precipitate that adds gained among the B again, stir, add xanthan rubber powder mix homogeneously then, reuse 15% polyvinylpyrrolidone 80% ethanol liquid system soft material, cross 20 mesh sieves and make wet granular, 50 ℃ of oven dry;

E, will dry granule and cross 20 mesh sieve granulate, add orange flavor essence, the magnesium stearate mixing of recipe quantity, tabletting, promptly.