CN102430122A - Fluoxertine hydrochloride orally disintegrating tablet and preparation method thereof - Google Patents
Fluoxertine hydrochloride orally disintegrating tablet and preparation method thereof Download PDFInfo
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- CN102430122A CN102430122A CN2011103943475A CN201110394347A CN102430122A CN 102430122 A CN102430122 A CN 102430122A CN 2011103943475 A CN2011103943475 A CN 2011103943475A CN 201110394347 A CN201110394347 A CN 201110394347A CN 102430122 A CN102430122 A CN 102430122A
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- oral cavity
- disintegration tablet
- cavity disintegration
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- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title abstract 6
- 239000006191 orally-disintegrating tablet Substances 0.000 title abstract 5
- 210000000214 mouth Anatomy 0.000 claims abstract description 56
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- 239000003456 ion exchange resin Substances 0.000 claims abstract description 31
- 229920003303 ion-exchange polymer Polymers 0.000 claims abstract description 31
- 239000003814 drug Substances 0.000 claims description 46
- 229920005989 resin Polymers 0.000 claims description 42
- 239000011347 resin Substances 0.000 claims description 42
- GIYXAJPCNFJEHY-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1) Chemical compound Cl.C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 GIYXAJPCNFJEHY-UHFFFAOYSA-N 0.000 claims description 40
- 229960000389 fluoxetine hydrochloride Drugs 0.000 claims description 40
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- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
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- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 description 1
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Abstract
The invention relates to a fluoxertine hydrochloride orally disintegrating tablet, in particular to an orally disintegrating tablet for masking a bitter taste of fluoxertine hydrochloride by adopting ion exchange resin. The fluoxertine hydrochloride orally disintegrating tablet can be rapidly disintegrated in an oral cavity, and the bitter taste of the fluoxertine hydrochloride can be completely masked. Moreover, the invention also relates to a preparation method for the fluoxertine hydrochloride orally disintegrating tablet.
Description
Technical field
The present invention relates to a kind of fluoxetine Hydrochloride oral cavity disintegration tablet and preparation method thereof, particularly a kind of oral cavity disintegration tablet that ion exchange resin carries out taste masking and preparation method thereof that adopts.
Background technology
Fluoxetine is the reuptake inhibitor of a kind of selectivity five hydroxytryptamine, optionally suppresses the reuptake after central nervous system's presynaptic five hydroxytryptamine discharges, thereby improves the concentration of synaptic space five hydroxytryptamine, produces tangible antidepressant effect.Because of it is very little to other neurotransmitter influences, so animal and human's brain is not had sedation.Abroad, this medicine has been widely used in the clinical treatment of depression.For this chemical compound oral administration is top-priority, and in order to reach this purpose and to guarantee to absorb rapidly the bioavailability of becoming reconciled, the form of the salt of solubility is top-priority, especially has good solubility and nontoxic hydrochlorate.Main sale is fluoxetine hydrochloride capsules in the market.But this single dosage form has seriously hindered the application of fluoxetine Hydrochloride.
Oral disintegrated preparation refer to can be in the oral cavity disintegrate or dissolved preparation rapidly, this type of preparation runs into saliva disintegrate and most of dissolving rapidly in the oral cavity, need not water and just can take.Oral disintegrated preparation comes across the later stage seventies 20th century, and employing Freeze Drying Techniques such as Gregory have been made the pharmaceutical carrier of high porosity, this carrier can be in 5～10 seconds after the oral cavity runs into saliva disintegrate complete.Oral cavity disintegration tablet has the advantage of solid dosage forms, for example: good stability, accurate dose, be easy to produce, little Package size, be easy to carry etc. for the patient.Oral cavity disintegration tablet also has the advantage of liquid dosage form, for example is easy to take, can as solid dosage forms, may stop up the danger that occurs suffocating because of physics.The commonplace crowd who is suitable for taking oral cavity disintegration tablet comprises the child, and the old people is bedfast, or the disability patient, and the patient of habitual vomiting, also has anhydrous people at one's side.Certainly the application of oral cavity disintegration tablet also can extend to the patient that need take heavy dose of medicine those every days.Because there is data to show that oral cavity disintegration tablet can reduce dosage under the prerequisite that does not affect the treatment.From the angle of pharmaceuticals industry, oral cavity disintegration tablet can be used as the new way that those patent protection periods are able to the protection of most medicine to continue.
Because tablet can be at Orally disintegrating, the rapid dispersing and dissolving of medicine also can be through buccal mucosa, pharyngeal, gastrointestinal region absorption.Therefore, the bioavailability of the quick acting of medicine and Geng Gao is possible.Because the absorption before the gastrointestinal can be avoided first pass effect, therefore for those through the tangible medicine of liver metabolism, its dosage can be cut down.
Oral disintegrated preparation more and more receives liking of patient with its unique advantages.Therefore have the people to imagine fluoxetine Hydrochloride is prepared into oral cavity disintegration tablet, but because the Orally disintegrating sector-meeting makes the drug component high degree of dispersion in the oral cavity on tongue after the disintegrate, it is clean to need the long period to be removed by excretory saliva.In addition, about 10,000 taste buds are arranged on the tongue according to statistics, nearly 60～100 recipient cells of each taste bud.These recipient cells react that can produce or the bad sense of taste with the medicine ion or the molecule that are dissolved in the saliva.Fluoxetine Hydrochloride has good water-solubility, in saliva of buccal cavity, has extremely bitter taste after the dissolving, considers the requirement of patient's compliance, and mouthfeel is to estimate one of most important parameter of oral drugs.Therefore if be prepared into oral cavity disintegration tablet, need fluoxetine Hydrochloride be carried out taste masking.Strong flavor or taste masking method at present relatively more commonly used mainly contain: the one, and can add correctives or sweeting agent for the medicine that slight disagreeable taste is arranged, but this method when being arranged for solution, the taste masking problem of medicine of utmost point bitter taste cuts little ice almost; Two are to use the polymer coating that in mouth, can protect drug component, active component is enclosed in the microcapsule, yet the not only complicated cost of this technology but also high also can bring bioequivalent problem; The 3rd, medicine activity component is used with the form that is insoluble in water; Though this method is feasible in theory; But in practice; Usually be difficult to find the dissolubility that makes drug component low, because tongue even can feel very small amount of material especially has the material of strong taste to complete insipid form in mouth.And when adopting this method, when obtaining the low solubility drugs form, can generate other high-dissolvability composition simultaneously usually, the height when this can cause oral cavity disintegration tablet in air, to be placed draws moist, and then influences the stability of oral cavity disintegration tablet.For example in the taste masking that utilizes sodium bicarbonate to ambroxol hydrochloride, though can access the low solubility form of ambroxol, the sodium chloride that generates simultaneously has and high draws moistly, and this has caused tablet very fast hygroscopic deformation under the condition of ambient temperature and moisture.In addition, absorb in the blood, also need after medicine is swallowed, the insoluble form of drug component dissolve immediately in order to make drug component.
Ion exchange resin is one type of functional macromolecule polymer, is applied to a plurality of fields such as water treatment, protein chemistry, analytical chemistry for a long time.From the 1950's, along with the continuous expansion of medicine controlled releasing drug-supplying system research, and the self-growth of polymer material science, ion exchange resin has begun to be used to delay drug release, to improve medicine stability etc.The theoretical basis that ion exchange resin is applied to medicine absorption be can dissociated acidity on the ion exchange resin or basic group can combine the insoluble medical resin of formation with the medicine of positively charged or negative electricity.This insoluble medical resin discharges medicine hardly under the pH of saliva of buccal cavity condition, and ion exchange resin itself is tasteless, therefore can not experienced any taste by tongue.And when medical resin got into the sour environment in gastro-intestinal digestion road, medicine can dissociate from resin moment, and with ionic form by fast Absorption.
The advantage that is used for taste masking just because of ion exchange resin; Therefore inventor's primary study of the present invention ion exchange resin cover up the bitterness of fluoxetine Hydrochloride; But find to adopt common ion exchange resin that fluoxetine Hydrochloride is carried out taste masking; Have following problem: at first the granule of conventional ion exchanger resin is all bigger, and generally in 0.3～1.2mm scope, major part is between 0.4～0.6mm for the size of resin particle.If adopt so big granule that medicine is adsorbed taste masking, when oral cavity disintegration tablet during disintegrate, though have the effect of well covering up bitterness, can make the people feel tangible sand feeling, even cause dysphagia in the oral cavity; In addition, the adsorption rate of conventional ion exchanger resin is all lower, and the absorption medication amount of common every gram ion exchanger resin is about 500 milligrams; Medicine for doses; Must adopt many above-mentioned ion exchange resin just can cover up the bitterness of medicine, will increase the weight and volume of tablet like this, this can cause the bad sensation in the oral cavity after the oral cavity disintegration tablet disintegrate equally; Particularly when adopting cryodesiccated method to prepare; Because the principle of its disintegrate is by means of the tablet high voidage, the disintegrate of the space of tablet owing to the rapid suction of capillarity, and use traditional ion exchange resin can cause the voidage of oral cavity disintegration tablet to reduce in a large number; Thereby cause the prolongation of disintegration time; And, need the amount of the ion exchange resin of interpolation also to increase accordingly, thereby possibly cause the quality standard of this oral cavity disintegration tablet not meet the relevant regulations that country formulates to oral cavity disintegration tablet for the strong dose thing thereupon.
Cover up fluoxetine Hydrochloride oral cavity disintegration tablet bitterness during disintegrate in the oral cavity so press for a kind of new method at present, thereby prepare the fluoxetine Hydrochloride oral cavity disintegration tablet.
Summary of the invention
Technical problem to be solved by this invention provides the bitterness that a kind of consumption ion exchange resin is seldom covered up fluoxetine Hydrochloride.And imperceptible sand feeling and disintegrate are rapid when utilizing the fluoxetine Hydrochloride oral cavity disintegration tablet Orally disintegrating of this ion exchange resin preparation.
The present invention provides a kind of method that is very suitable for preparing above-mentioned fluoxetine Hydrochloride oral cavity disintegration tablet on the other hand.
The oral cavity disintegration tablet that the present invention relates to comprises:
Fluoxetine Hydrochloride, ion exchange resin Amberlite IRP88 and other be the acceptable adjuvant pharmaceutically.Ion exchange resin Amberlite IRP88 is the copolymer of methacrylic acid and DVB Diethenylbenzene; It is a kind of Subacidity cation type exchanger resin; Its particle size distribution is 10～120 microns, and 70% below 50 microns, is produced by U.S. Rhom and Hass (Rohm&Haas Ltd.).
Above-described adjuvant comprises binding agent, skeleton proppant, suspensoid, can also add other sweeting agent, aromatic etc. as required.The binding agent that the people knew of this area was preferred when described binding agent can be the preparation oral cavity disintegration tablet, was selected from dextran, Pullulan, sodium alginate, polyvinyl alcohol, chitosan; More preferably dextran, Pullulan, sodium alginate or their mixture, preferred especially Pullulan; Described skeleton proppant can be the adjuvant that plays skeleton support effect known to those of skill in the art; Preferably; Be selected from sugar, sugar alcohol, inorganic salt, aminoacid or above mixture; More preferably sugar alcohol and aminoacid particularly preferably are mannitol, erythritol, glycine, serine, arginine or their mixture, most preferably mannitol and glycine.
Because it is water insoluble that the usefulness that the present invention relates to has been adsorbed the ion exchange resin of medicine; Therefore need to add suspensoid; Suspensoid involved in the present invention can be any suspensoid of this area; Preferably, be selected from arabic gum, xanthan gum, carbomer, agarose, Konjac glucomannan, more preferably xanthan gum.
The preparation of the fluoxetine Hydrochloride oral cavity disintegration tablet that the present invention relates to can be adopted all methods of the preparation oral cavity disintegration tablet of present employing, for example direct compression process, freeze-drying etc.
When adopting direct compression process to prepare the oral cavity disintegration tablet that the present invention relates to, must add disintegrating agent, common disintegrating agent has sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose.
In addition, when the oral cavity disintegration tablet that adopts the direct compression process preparation the present invention relates to,, make its mix homogeneously, can also add such as magnesium stearate, the such fluidizer of silicon dioxide in order to increase the flowability of medicine and adjuvant.
The oral cavity disintegration tablet that preparation the present invention relates to preferably adopts freeze-drying, and described freeze-drying comprises:
The medical resin that a) will be loaded with fluoxetine mixes with described excipient substance in certain prescription ratio, then freezing;
B),, obtain the agent of porous feeler through dry with above-mentioned refrigerated solution for vacuum sublimation drying.
Another aspect of the present invention provides a kind of method for preparing above-mentioned fluoxetine Hydrochloride oral cavity disintegration tablet, and this method comprises:
A) ion exchange resin Amberlite IRP88 is placed container, add certain density fluoxetine Hydrochloride solution then, fully stir;
B) solution left standstill that a) step is obtained is removed supernatant then, has obtained adsorbing the ion exchange resin of medicine;
C) repeat a) step, no longer change up to the supernatant concentration of taking out is the same with the concentration that adds fashionable fluoxetine Hydrochloride.
The concentration of the fluoxetine Hydrochloride that in said method, adopts is 8-14mg/ml, but 14mg/ml more preferably.
The specific embodiment
Below through the detailed explanation the present invention of embodiment.
The assay method of ion exchange resin adsorption rate:
The resin of getting it filled is an amount of, and accurate the title decides, and puts into and puts conical flask; Add 1mol/l HCl solution 250ml, under 60 ℃ of conditions, constant temperature jolting 2 hours; Filter; Get subsequent filtrate and measure absorbance at the 226nm place, calculate the content of medical resin Chinese medicine, and then draw the adsorption rate of ion exchange resin medicine.
Embodiment 1
Fluoxetine Hydrochloride (general Lip river, the Zhejiang chemical industry company limited) solution of configuration 14mg/ml joins in the beaker that fills 10mg cation exchange resin Amberlite IRP88 (production of Rohm&Haas company) then, evenly stirs 2 hours; Leave standstill; Remove supernatant, precipitate is used deionized water wash, then adds the fluoxetine Hydrochloride solution of 14mg/ml again; Repeat above-mentioned steps, till the concentration of supernatant is 14mg/ml.Be drying to obtain medical resin at 40 ℃ at last.
Through analyzing, the fluoxetine Hydrochloride that records every gram Amberlite IRP88 absorption in the said medicine resin is 2.00 grams.
(Hayashibara Co.Ltd., Japan) mixing add an amount of purified water, and room temperature is stirred well to whole dissolvings with 12mg glycine (Beijing essence is asked chemical industry Co., Ltd) and 14mg Pullulan; With 0.32mg xanthan gum (Beijing pharmaceutcal corporation, Ltd of Shenhua) separately with after the abundant swelling of purified water; The medical resin that adds above-mentioned preparation then; Mixing, then with above-mentioned glycine and Pullulan solution mix homogeneously after, add an amount of purified water; Make that the total amount of the above purified water that all adds is 343.68mg, make the medical resin medicinal liquid; Medical resin medicinal liquid vacuum stirring is outgased; Use electronic liquor-transferring rifle (Beijing Ji Nuosi scientific & trading Co., Ltd., 720110) accurately to be injected in 0.4 milliliter of mould then; Through liquid nitrogen (the practical gas company limited of Beijing Praxair, XL-45) spray refrigeration at-110 ℃ after freezing 5 minutes; Change freeze dryer (day Science and Technology Ltd. during Beijing speed is former over to; GLZ-0.8) in, lyophilizing is 5 hours under 0.5 millibar of pressure ,-20 ℃ to 25 ℃ condition, promptly obtains fluoxetine Hydrochloride oral cavity disintegration tablet of the present invention.
Embodiment 2
The fluoxetine Hydrochloride solution of configuration 8mg/ml joins in the beaker that fills 9.5mg cation exchange resin Amberlite IRP88 then, evenly stirs 4 hours; Leave standstill; Remove supernatant, precipitate is used deionized water wash, then adds the fluoxetine Hydrochloride solution of 8mg/ml again; Repeat above-mentioned steps, till the concentration of supernatant is 8mg/ml.Be drying to obtain medical resin at 40 ℃ at last.
Through analyzing, the fluoxetine Hydrochloride that records every gram Amberlite IRP88 absorption in the said medicine resin is 2.10 grams.
With 12mg mannitol (Beijing essence is asked chemical industry Co., Ltd) and 16mg Pullulan mixing, add an amount of purified water, room temperature is stirred well to whole dissolvings; With the 0.32mg xanthan gum separately with after the abundant swelling of purified water; The medical resin that adds above-mentioned preparation then; Mixing, then with above-mentioned mannitol and Pullulan solution mix homogeneously after, add an amount of purified water; Make that the total amount of the above purified water that all adds is 342.18mg, make the medical resin medicinal liquid; Medical resin medicinal liquid vacuum stirring is outgased; Use the electronic liquor-transferring rifle accurately to be injected in 0.4 milliliter of mould then; Through liquid nitrogen spraying refrigeration at-120 ℃ after freezing 4 minutes; Change in the freeze dryer, lyophilizing is 6 hours under 0.5 millibar of pressure ,-20 ℃ to 25 ℃ condition, promptly obtains fluoxetine Hydrochloride oral cavity disintegration tablet of the present invention.
Embodiment 3
The fluoxetine Hydrochloride solution of configuration 14mg/ml joins in the beaker that fills 9.6mg cation exchange resin Amberlite IRP88 then, evenly stirs 2 hours; Leave standstill; Remove supernatant, precipitate is used deionized water wash, then adds the fluoxetine Hydrochloride solution of 14mg/ml again; Repeat above-mentioned steps, till the concentration of supernatant is 14mg/ml.Be drying to obtain medical resin at 40 ℃ at last.
Through analyzing, the fluoxetine Hydrochloride that records every gram Amberlite IRP88 absorption in the said medicine resin is 2.08 grams.
Dextran 40 (Jiangsu Province's Huanghai Sea pharmaceutcal corporation, Ltd) mixing with 10mg glycine and 10mg Pullulan and 6mg adds an amount of purified water, and room temperature is stirred well to whole dissolvings; With the 0.32mg xanthan gum separately with after the abundant swelling of purified water; The medical resin that adds above-mentioned preparation then; Mixing, then with above-mentioned glycine, Pullulan and Dextran 40 solution mix homogeneously after, add an amount of purified water; Make that the total amount of the above purified water that all adds is 344.08mg, make the medical resin medicinal liquid; Medical resin medicinal liquid vacuum stirring is outgased; Use the electronic liquor-transferring rifle accurately to be injected in 0.4 milliliter of mould then; Through liquid nitrogen spraying refrigeration at-120 ℃ after freezing 5 minutes; Change in the freeze dryer, lyophilizing is 5 hours under 0.5 millibar of pressure ,-20 ℃ to 25 ℃ condition, promptly obtains fluoxetine Hydrochloride oral cavity disintegration tablet of the present invention.
Embodiment 4
The fluoxetine Hydrochloride solution of configuration 14mg/ml joins in the beaker that fills 9.9mg cation exchange resin Amberlite IRP88 then, evenly stirs 2 hours; Leave standstill; Remove supernatant, precipitate is used deionized water wash, then adds the fluoxetine Hydrochloride solution of 14mg/ml again; Repeat above-mentioned steps, till the concentration of supernatant is 14mg/ml.Be drying to obtain medical resin at 40 ℃ at last.
Through analyzing, the fluoxetine Hydrochloride that records every gram Amberlite IRP88 absorption in the said medicine resin is 2.01 grams.
Low replacement carboxy-propyl cellulose, the 26.92mg microcrystalline Cellulose of 242.28mg are mixed with the dehydrated alcohol wet granulation; Mix with magnesium stearate and the above-mentioned medical resin that obtains of 39mg again through 60 ℃ of dryings; Stir; Use direct compression machine direct compression then, the fluoxetine Hydrochloride oral cavity disintegration tablet that obtains the present invention relates to.
The mensuration of comparative example ion exchange resin adsorption rate commonly used
Comparative example 1
Except ion exchange resin Amberlite IRP88 is changed into the Amberlite IRP64, remaining is the same with embodiment 1, prepares the medical resin with Amberlite IRP64 taste masking.
Carry out the mensuration of ion exchange resin adsorption rate for the medical resin of method for preparing, the fluoxetine Hydrochloride that obtains every gram ion exchanger resin Amberlite IRP69 absorption is 0.35 gram.
Comparative example 2
Except ion exchange resin Amberlite IRP88 is changed into the Amberlite IRP69, remaining is the same with embodiment 1, prepares the medical resin with Amberlite IRP69 taste masking.
Carry out the mensuration of ion exchange resin adsorption rate for the medical resin of method for preparing, the fluoxetine Hydrochloride that obtains every gram ion exchanger resin Amberlite IRP69 absorption is 0.75 gram.
Claims (20)
1. the medical resin compositions of a high adsorption capacity is characterized in that the medicine accounting is 66.67%-67.53%.
2. medical resin compositions, the medicine that it is characterized in that every gram resin absorption are 2.00～2.10 grams.
3. like each described medical resin compositions of claim 1-2, the medicine that it is characterized in that every gram resin absorption is 2.00 grams, or 2.08 grams, or 2.10 grams, or 2.01 grams.
4. like each described medical resin compositions of claim 1-3, it is characterized in that described medicine is a fluoxetine Hydrochloride.
5. like each described medical resin compositions of claim 1-4, it is characterized in that described resin is a cation exchange resin, preferred Amberlite IRP88.
6. oral cavity disintegration tablet is characterized in that comprising pharmaceutically acceptable adjuvant of each described medical resin compositions of claim 1-5 and other, preferably adopts the freeze-drying preparation.
7. oral cavity disintegration tablet as claimed in claim 6, wherein said adjuvant comprise binding agent, skeleton proppant, suspensoid.
8. oral cavity disintegration tablet as claimed in claim 7, wherein said binding agent is selected from dextran, Pullulan, sodium alginate, polyvinyl alcohol, chitosan.
9. oral cavity disintegration tablet as claimed in claim 8, wherein said binding agent is selected from dextran, Pullulan.
10. oral cavity disintegration tablet as claimed in claim 9, wherein said binding agent are Pullulan.
11. oral cavity disintegration tablet as claimed in claim 7, wherein said skeleton proppant is selected from sugar, sugar alcohol, inorganic salt and aminoacid.
12. oral cavity disintegration tablet as claimed in claim 11, wherein said sugar alcohol is selected from mannitol, erythritol.
13. oral cavity disintegration tablet as claimed in claim 11, wherein said aminoacid is selected from glycine, serine, arginine.
14. oral cavity disintegration tablet as claimed in claim 7, wherein said suspensoid is selected from arabic gum, xanthan gum, carbomer, agarose, Konjac glucomannan.
15. oral cavity disintegration tablet as claimed in claim 14, wherein said suspensoid are xanthan gum.
16. like each described medical resin compositions of claim 1-5, its preparation method is the simulation dynamic method of non-static method.
17. medical resin preparation of compositions method as claimed in claim 16 comprises:
A) ion exchange resin is placed container, add two fun gi polysaccharides solution then, fully stir;
B) solution left standstill that a) step is obtained is removed supernatant then, has obtained adsorbing the ion exchange resin of medicine;
C) repeat a) step, up to the supernatant concentration of taking out with add that fashionable drug level is identical no longer to change.
18. the method for preparing like each described oral cavity disintegration tablet of claim 6-15 comprises:
A) ion exchange resin is placed container, add two fun gi polysaccharides solution then, fully stir;
B) solution left standstill that a) step is obtained is removed supernatant then, has obtained adsorbing the ion exchange resin of medicine;
C) repeat a) step, up to the supernatant concentration of taking out with add that fashionable drug level is identical no longer to change.
19. like claim 17,18 each described method for preparinies, wherein said fluoxetine Hydrochloride solution is 8-14mg/ml, preferred 14mg/ml.
20. like each described oral cavity disintegration tablet of claim 6-15, it is characterized in that method for preparing is following: with binding agent and skeleton proppant mixing, add an amount of purified water, room temperature is stirred well to whole dissolvings; Suspensoid separately with after the abundant swelling of purified water, is added the medical resin compositions prepare then, mixing, then with the solution mix homogeneously of above-mentioned binding agent and skeleton proppant after, add an amount of purified water, make the medical resin medicinal liquid; Medical resin medicinal liquid vacuum stirring is outgased; Use the electronic liquor-transferring rifle accurately to be injected in 0.4 milliliter of mould then, at-120 ℃ after freezing 4 minutes, change in the freeze dryer through liquid nitrogen spraying refrigeration; Lyophilizing is 6 hours under 0.5 millibar of pressure ,-20 ℃ to 25 ℃ condition, promptly gets.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103943475A CN102430122A (en) | 2005-12-13 | 2005-12-13 | Fluoxertine hydrochloride orally disintegrating tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103943475A CN102430122A (en) | 2005-12-13 | 2005-12-13 | Fluoxertine hydrochloride orally disintegrating tablet and preparation method thereof |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510129939 Division CN1981746A (en) | 2005-12-13 | 2005-12-13 | Fluoxetine hydrochloride oral disintegrant tablets and their production |
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| CN102430122A true CN102430122A (en) | 2012-05-02 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105232502A (en) * | 2015-02-10 | 2016-01-13 | 万全万特制药江苏有限公司 | Orally disintegrating tablet containing polacrilin potassium-fluoxertine hydrochloride compound and preparation method of orally disintegrating tablet |
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| CN1140411A (en) * | 1994-02-03 | 1997-01-15 | 史密丝克莱恩比彻姆有限公司 | Oral liquid compositions contg. paroxetine resinate |
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| CN105232502A (en) * | 2015-02-10 | 2016-01-13 | 万全万特制药江苏有限公司 | Orally disintegrating tablet containing polacrilin potassium-fluoxertine hydrochloride compound and preparation method of orally disintegrating tablet |
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Application publication date: 20120502 |