CN1935140A - Compound diphenidol hydrochloride dispersible tablet, and its preparing method - Google Patents
Compound diphenidol hydrochloride dispersible tablet, and its preparing method Download PDFInfo
- Publication number
- CN1935140A CN1935140A CN 200510103521 CN200510103521A CN1935140A CN 1935140 A CN1935140 A CN 1935140A CN 200510103521 CN200510103521 CN 200510103521 CN 200510103521 A CN200510103521 A CN 200510103521A CN 1935140 A CN1935140 A CN 1935140A
- Authority
- CN
- China
- Prior art keywords
- mixture
- difenidol hydrochloride
- disintegrating agent
- dispersible tablet
- diluent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000007919 dispersible tablet Substances 0.000 title claims description 42
- 238000000034 method Methods 0.000 title claims description 18
- -1 Compound diphenidol hydrochloride Chemical class 0.000 title description 2
- 229960005058 diphenidol hydrochloride Drugs 0.000 title description 2
- 229960003520 diphenidol Drugs 0.000 claims abstract description 66
- OGAKLTJNUQRZJU-UHFFFAOYSA-N diphenidol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)CCCN1CCCCC1 OGAKLTJNUQRZJU-UHFFFAOYSA-N 0.000 claims abstract description 65
- 239000000203 mixture Substances 0.000 claims abstract description 64
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 37
- 229920002472 Starch Polymers 0.000 claims abstract description 24
- 238000002360 preparation method Methods 0.000 claims abstract description 24
- 239000008107 starch Substances 0.000 claims abstract description 24
- 235000019698 starch Nutrition 0.000 claims abstract description 24
- 239000003085 diluting agent Substances 0.000 claims abstract description 23
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 14
- 239000000463 material Substances 0.000 claims abstract description 12
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 10
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 10
- 239000011734 sodium Substances 0.000 claims abstract description 10
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 10
- 239000003826 tablet Substances 0.000 claims description 26
- 238000002156 mixing Methods 0.000 claims description 25
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 21
- 239000007864 aqueous solution Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 16
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 16
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 16
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 16
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 16
- 229960003943 hypromellose Drugs 0.000 claims description 16
- 239000008101 lactose Substances 0.000 claims description 16
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 16
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 16
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 16
- 239000002671 adjuvant Substances 0.000 claims description 15
- 239000011230 binding agent Substances 0.000 claims description 14
- 239000008187 granular material Substances 0.000 claims description 13
- 239000007779 soft material Substances 0.000 claims description 12
- 235000019359 magnesium stearate Nutrition 0.000 claims description 11
- 230000001476 alcoholic effect Effects 0.000 claims description 10
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims description 8
- 239000007968 orange flavor Substances 0.000 claims description 8
- 239000002002 slurry Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 238000012856 packing Methods 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- 229920001353 Dextrin Polymers 0.000 claims description 6
- 239000004375 Dextrin Substances 0.000 claims description 6
- 229920000881 Modified starch Polymers 0.000 claims description 6
- 235000019425 dextrin Nutrition 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 239000004615 ingredient Substances 0.000 claims description 6
- 235000000346 sugar Nutrition 0.000 claims description 6
- 239000000945 filler Substances 0.000 claims description 5
- 238000005498 polishing Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 abstract description 10
- 239000006185 dispersion Substances 0.000 abstract description 2
- 239000000853 adhesive Substances 0.000 abstract 1
- 230000001070 adhesive effect Effects 0.000 abstract 1
- 238000004090 dissolution Methods 0.000 description 19
- 239000012738 dissolution medium Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 238000005303 weighing Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- 208000012886 Vertigo Diseases 0.000 description 6
- 231100000889 vertigo Toxicity 0.000 description 6
- 239000012530 fluid Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 235000019658 bitter taste Nutrition 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000012982 microporous membrane Substances 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 206010029864 nystagmus Diseases 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 231100000643 Substance intoxication Toxicity 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 210000001841 basilar artery Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000012633 leachable Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000003152 motion sickness Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000003405 preventing effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035943 smell Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000001720 vestibular Effects 0.000 description 1
- 210000003273 vestibular nerve Anatomy 0.000 description 1
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a difenidol hydrochloride dispersion tablet preparation and its preparation method. Its composition includes (by wt%) 10%-50% of difenidol hydrochloride and 50%-90% of auxiliary material, in the auxiliary material the disintegrating agent content is 5%-20% of whole medicine component, said disintegrating agent can be one kind of cross-linked PVP, low-substituted hydroxypropyl cellulose and carboxymethyl starch sodium or their mixture. The auxiliary material also includes one kind of diluting agent, adhesive, corrective and flow aid or their mixture.
Description
Technical field
The present invention relates to a kind of difenidol hydrochloride dispersible tablet and preparation method thereof, the difenidol hydrochloride dispersible tablet is the novel form that is used for the vertigo medicine, difenidol hydrochloride can increase awl basilar artery blood flow, regulates the unusual impulsion of vestibular nerve, suppresses vomiting center and improves nystagmus.Specifically the difenidol hydrochloride conventional tablet that former Chinese Pharmacopoeia is recorded is changed into the preparation method of dispersible tablet and said preparation.
Background technology
One of the normal at present Therapeutic Method that uses of vertigo and medicine of use are with difenidol hydrochloride tablet or injection.The tremulous pulse blood supply was not complete at the bottom of difenidol hydrochloride can improve vertebra, and vestibular nervous system is had regulating action, and various centrals, tip vertigo are had therapeutical effect; Other has the town to tell and suppresses the nystagmus effect, but anti-kinetosis; Also also has the weak anti-M of property-choline effect on every side.Oral this product is through gastrointestinal absorption, and the back 1.5～3h blood drug level of taking medicine reaches the peak.t
1/2Be 4h.Medicine is discharged from urine with original shape.Be mainly used in the dizzy and vomiting that multiple disease causes, as bore end tremulous pulse blood supply insufficiency, Meniere, autonomic nervous dysfunction, hypertension, hypotension, cervical vertigo, drug intoxication etc., also be used for the vomiting after the surgery anesthesia, motion sickness is had prevention and therapeutical effect.
The tool of difenidol hydrochloride own is slightly water-soluble, the character of bitter in the mouth, and its dissolution rate and degree are the speed limit process that absorbs, and be directly related with curative effect.Its conventional tablet is a coated tablet, and the performance curative effect is slower, needs the disintegrate of 30-45 minute ability, performance curative effect usually, and need quick acting when vertigo is treated.Simultaneously, for carsick, seasick personnel is prophylactic treatment, but general difficulty accomplishes that shifting to an earlier date 30-60 minute takes medicine, and takes medicine after get on the bus (ship) because former coated tablet onset is slow temporarily, often carsick (ship) back medicine does not also produce curative effect, so do not have due pre-anti-dazzle effect.Its bitterness has also brought inconvenience to the patient in addition.Therefore, a kind of onset of needs is rapid, the difenidol hydrochloride novel form of features good taste, to satisfy the needs of vertigo prevention, treatment.
Summary of the invention
Technical problem to be solved by this invention is at above-mentioned weak point of the prior art, provides a kind of and responds well to treatment soon, can improve its bitterness again, the tablet formulation of long-term storage efficacy stability---difenidol hydrochloride dispersible tablet and preparation method thereof.
The technical scheme that solution the technology of the present invention problem is adopted is that this difenidol hydrochloride dispersible tablet is in its dispersible tablet formulation, ingredient comprises principal agent difenidol hydrochloride and adjuvant, contain disintegrating agent in the adjuvant, its percentage by weight consists of: difenidol hydrochloride 10%-50%, adjuvant 50%-90%, disintegrating agent accounts for the 5%-20% of whole ingredient in the adjuvant.Disintegrating agent can be one or more the mixture in cross-linked pvp, low-substituted hydroxypropyl cellulose, the carboxymethyl starch sodium.
Also comprise in the adjuvant in the difenidol hydrochloride dispersible tablet provided by the invention: 1, diluent is a filler, can be one or more mixture 2, the binding agent in microcrystalline Cellulose, lactose, powdered sugar, starch, dextrin, the pregelatinized Starch, can be the aqueous solution of 2%-10% starch slurry, 2%-10% hypromellose or 2%-10%PVP or one or more the mixture in the alcoholic solution; 3, correctives can be one or more the mixture in Herba Menthae essence, flavoring orange essence, the orange flavor; 4, fluidizer is that polishing material can be one or more the mixture in magnesium stearate, the micropowder silica gel.
Preferably, in per 1000 tablet preparations of difenidol hydrochloride dispersible tablet of the present invention,
Difenidol hydrochloride 25g
Adjuvant 25～1975g
Further preferably, in per 1000 tablet preparations of difenidol hydrochloride dispersible tablet of the present invention, the composition proportion scope is:
Difenidol hydrochloride 25g
Diluent 0～1970g
Disintegrating agent 2.5～400g
The preparation method of difenidol hydrochloride dispersible tablet of the present invention is pressed in per 1000 tablet preparations of difenidol hydrochloride dispersible tablet, and the composition proportion scope is:
Difenidol hydrochloride 25g
Diluent 0～1970g
Disintegrating agent 2.5～400g
Its preparation may further comprise the steps:
1, get the diluent of proportional quantity, fully mixing gets diluent mixture; Or a part (determining addition) of getting the disintegrating agent of the diluent of proportional quantity and proportional quantity by the interior forwarding method that adds, abundant mixing, the mixture of diluent and disintegrating agent; Diluent is a filler, can be one or more the mixture in microcrystalline Cellulose, lactose, powdered sugar, starch, dextrin, the pregelatinized Starch; Disintegrating agent can be one or more the mixture in cross-linked pvp, low-substituted hydroxypropyl cellulose, the carboxymethyl starch sodium;
2, get the difenidol hydrochloride of proportional quantity, adopt the equivalent method of progressively increasing to add that mixing gets mixture in the diluent of step 1 gained;
3, the binding agent of getting proportional quantity adds in the mixture of step 2, and the limit edged stirs, and makes soft material; Binding agent can be the aqueous solution of starch slurry, hypromellose or PVP or one or more the mixture in the alcoholic solution;
4, soft material is crossed the 10-30 mesh sieve and made wet granular;
5, with wet granular in 50-80 ℃ of dried granule that is dried to water content 1%-8%;
6, the disintegrating agent, correctives and the fluidizer that remain in the disintegrating agent of adding proportional quantity or the step 1 in the dried granule that step 5 is made or the mixture of step 2, mixing, tabletting, packing, promptly.Disintegrating agent can be one or more the mixture in cross-linked pvp, low-substituted hydroxypropyl cellulose, the carboxymethyl starch sodium; Correctives can be one or more the mixture in Herba Menthae essence, flavoring orange essence, the orange flavor; Fluidizer is that polishing material can be one or more the mixture in magnesium stearate, the micropowder silica gel.
The present invention adopts the mode of wet granule compression tablet or dry powder direct tabletting, is principal agent with the difenidol hydrochloride, cooperates with other adjuvants, makes dispersible tablet.Compare with former preparation conventional tablet, preparation stabilization, produce effects is fast, does not have bad abnormal smells from the patient, the convenient use; Simultaneously, add correctives, reduced the bitterness that produces when tablet stops in the oral cavity.Thereby curative effect and patient's compliance have been strengthened.Simultaneously, the present invention writes out a prescription and adopts cross-linked pvp, low-substituted hydroxypropyl cellulose, the powerful disintegrating agent of carboxymethyl starch sodium, (disintegrate in 10 seconds, release reach 90% to make the rapid disintegrate dispersion of difenidol hydrochloride, former ordinary tablet is that 30-60 minute ability discharges 90%), the stripping and the absorption of difenidol hydrochloride have been accelerated, having shortened effective time (just energy onset in 5 minutes), is a kind of good dosage form.The quick dissolution token test research of difenidol hydrochloride dispersible tablet of the present invention
Set up the dissolution determination method of this product with reference to two appendix XC of Chinese Pharmacopoeia version in 2000.Adopt the HPLC method to measure the concentration of dissolution fluid.
Instrument: RC-3B medicament dissolution instrument (Radio Factory of Tianjin Univ.), Tianjin, island LC-10A chromatograph, SPD-6AV UV-detector, AE-200 electronic analytical balance (METTLER).
The selection of dissolution medium
According to the principle of first-selected water of ordinary preparation dissolution study and 0.1mol/L hydrochloric acid, be dissolution medium with water and 0.1mol/L hydrochloric acid 900ml respectively.With reference to two appendix XC of Chinese Pharmacopoeia version in 2000 dissolution determination, second method, the stirring arm rotating speed is made as 75 rev/mins, gets the filtering with microporous membrane that solution 5ml uses 0.8 μ m immediately through 30 minutes, gets subsequent filtrate; In addition precision take by weighing through 105 ℃ of difenidol hydrochloride reference substances that are dried to constant weight an amount of, water and 0.1mol/L dissolving with hydrochloric acid and the dilution solution product solution in contrast of making hydrochloric approximately diphenidol 25 μ g among the 1ml respectively.Get each 20 μ l of above-mentioned solution and inject chromatograph of liquid, calculate dissolution, relatively the stripping situation in two kinds of dissolution mediums.The results are shown in following table 1.This product goes out stripping is preferably all arranged in water and 0.1mol/L hydrochloric acid, so optional water is as dissolution medium.
The selection of rotating speed
With water is dissolution medium, change the speed of stirring arm, investigate the influence of rotating speed to stripping, got the filtering with microporous membrane that solution 5ml uses 0.8 μ m immediately through 30 minutes, get subsequent filtrate 2ml and put in the 10ml volumetric flask, water is released to scale, measures content according to the HPLC method, calculate dissolution, relatively the stripping situation under different rotating speeds.Stripping under the different rotating speeds the results are shown in Table 2.75 rev/mins and 100 rev/mins of all strippings preferably.Select 50 rev/mins of the more weak relatively rotating speeds of leaching condition.
The stability of sample in dissolution medium
Get 1 part of above dissolution fluid, room temperature was placed 2 hours, and in 0h, 0.5h, 1h measures content during 2h, investigate the stability of sample in dissolution medium.Results sample room temperature shelf-stability in dissolution medium is good, can satisfy the accuracy of measurement result.See Table 3.
The stripping homogeneity is investigated
Get lot number and be 6 in 040919 tablet, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000), be dissolution medium with water 900ml, rotating speed is 75 rev/mins, temperature is 37 ± 0.5 ℃, operation in accordance with the law is respectively at 5,10,15,30,45 minutes sampling 5ml add the dissolution medium with volume after each sampling.The sample that takes out is used the filtering with microporous membrane of 0.8 μ m immediately, gets subsequent filtrate 2ml and puts in the 10ml volumetric flask, is diluted with water to scale as need testing solution.It is an amount of that in addition precision takes by weighing the difenidol hydrochloride reference substance, is mixed with the solution of the hydrochloric diphenidol 25 μ g of every ml, product solution in contrast with water dissolution.Measure the peak area of record need testing solution and reference substance solution according to the HPLC method.The peak area of dissolution fluid is compared with the peak area that contrasts liquid, get the concentration of each time point dissolution fluid, and then obtain the accumulation stripping percentage rate of each time point, relatively the stripping homogeneity of 6 stripping rotors.The results are shown in Table 4.Annotate: RSD is a relative standard deviation.
The stripping curve of self-control sample
Get respectively 6 of this product (040919,040920,040921) respectively,, get the stripping curve data and see Table 5 according to " investigation of a stripping homogeneity " operation down.The result shows that this product is a dissolution medium with water 900ml, and 15 minutes is leachable 90%.
Dispersible tablet and the dissolution comparative study that has listing kind ordinary tablet now
Respectively difenidol hydrochloride ordinary tablet and dispersible tablet are measured stripping curve as stated above respectively, the results are shown in Figure 1.
Fig. 1 shows that 5 minutes dissolutions of ordinary tablet are 10%, and dispersible tablet is 70%, is 7 times of ordinary tablet; The ordinary tablet stripping more than 80% the needed time be 30 minutes, and dispersible tablet is less than 10 minutes, so dispersible tablet is fast than the obvious stripping of ordinary tablet.
Description of drawings
The stripping curve comparison diagram of Fig. 1 ordinary tablet (coated tablet) and dispersible tablet of the present invention
The specific embodiment
When difenidol hydrochloride dispersible tablet of the present invention was selected different adjuvants for use, in per 1000 tablet preparations, the preferable consumption of its adjuvant was respectively:
1. diluent (filler): 1～1970g
Can adopt one or more the mixture in microcrystalline Cellulose, lactose, powdered sugar, starch, dextrin, the pregelatinized Starch, when two or more mixing diluents is used: when mixing use with lactose as microcrystalline Cellulose, then microcrystalline Cellulose 1～1970g, lactose 0～1969g.
2. disintegrating agent: 2.5～400g
Can adopt one or more the mixture in cross-linked pvp, low-substituted hydroxypropyl cellulose, the carboxymethyl starch sodium, two or more disintegrating agent mixes when using: when mixing use with low-substituted hydroxypropyl cellulose as cross-linked pvp, and then cross-linked pvp 1～200g, low-substituted hydroxypropyl cellulose 1.5～399g.
3. binding agent: 5～600ml
Can adopt the aqueous solution of starch slurry (2%-10%), hypromellose (2%-10%) aqueous solution or alcoholic solution, PVP (2%-10%) or one or more the mixture in the alcoholic solution, two or more binding agent mixes when using: when mixing use with hypromellose (2%-10%) aqueous solution or alcoholic solution as starch slurry (2%-10%), and then starch slurry (2%-10%) 3～300ml, hypromellose (2%-10%) aqueous solution or alcoholic solution 2～597ml.
4. correctives: 1～40g
Can adopt one or more the mixture when using (mix can in arbitrary ratio) in Herba Menthae essence, flavoring orange essence, the orange flavor.
5. fluidizer is a polishing material: 6～40g
Can adopt the mixture of a kind of in magnesium stearate, the micropowder silica gel or two kinds, two kinds of fluidizer mix when using: can be magnesium stearate 3～10g and micropowder silica gel 3～37g.
Below be non-limiting examples of the present invention:
Embodiment 1:
Per 1000 difenidol hydrochloride dispersible tablet formulations take by weighing material by following prescription:
Difenidol hydrochloride 25g
Microcrystalline Cellulose 135g
Lactose 75g
Cross-linked pvp 12g
5% hypromellose aqueous solution 40ml
Magnesium stearate 3g
Orange flavor 2g
The raw material that takes by weighing is prepared difenidol hydrochloride dispersible tablet of the present invention according to the following steps:
1, gets microcrystalline Cellulose 135g, lactose 75g, cross-linked pvp (ratio that accounts for whole disintegrating agent total amount in the amount of the disintegrating agent of this adding is sent definitely by interior adding, and this adding method is called Nei Jiafa, is professional method) 6g, mixing;
2, get the difenidol hydrochloride of proportional quantity, adopt the equivalent method of progressively increasing to add in step 1 mixture, fully mixing;
3, get 5% hypromellose aqueous solution of proportional quantity, slowly add in step 2 mixture, the limit edged stirs, and makes soft material;
4, soft material is crossed 14 mesh sieves and made wet granular;
5, with wet granular in the dried granule that is dried to water content about 3% about 70 ℃;
6, the disintegrating agent and correctives and the fluidizer that the dried granule of step 5 are added surplus, mixing, tabletting, every heavy 250mg, packing, promptly.
Embodiment 2
Per 1000 difenidol hydrochloride dispersible tablet formulations take by weighing material by following prescription:
Difenidol hydrochloride 25g
Microcrystalline Cellulose 135g
Lactose 75g
Low-substituted hydroxypropyl cellulose 12g
5% hypromellose aqueous solution 40ml
Magnesium stearate 3g
Flavoring orange essence 2g
The raw material that takes by weighing is prepared difenidol hydrochloride dispersible tablet of the present invention according to the following steps:
1, gets microcrystalline Cellulose 135g, lactose 75g, low-substituted hydroxypropyl cellulose 6g, mixing;
2, get the difenidol hydrochloride of proportional quantity, adopt the equivalent method of progressively increasing to add in step 1 mixture, fully mixing;
3, get 5% hypromellose aqueous solution of proportional quantity, slowly add in step 2 mixture, the limit edged stirs, and makes soft material;
4, soft material is crossed 14 mesh sieves and made wet granular;
5, with wet granular in the dried granule that is dried to water content about 3% about 70 ℃;
6, the disintegrating agent and correctives and the fluidizer that the dried granule of step 5 are added surplus, mixing, tabletting, every heavy 250mg, packing, promptly.
Embodiment 3
Per 1000 difenidol hydrochloride dispersible tablet formulations take by weighing material by following prescription:
Difenidol hydrochloride 25g
Microcrystalline Cellulose 135g
Lactose 75g
Carboxymethyl starch sodium 12g
5% hypromellose aqueous solution 40ml
Magnesium stearate 3g
Herba Menthae essence 2g
The raw material that takes by weighing is prepared difenidol hydrochloride dispersible tablet of the present invention according to the following steps:
1, gets microcrystalline Cellulose 135g, lactose 75g, carboxymethyl starch sodium 6g, mixing;
2, get the difenidol hydrochloride of proportional quantity, adopt the equivalent method of progressively increasing to add in step 1 mixture, fully mixing;
3, get 5% hypromellose aqueous solution of proportional quantity, slowly add in step 2 mixture, the limit edged stirs, and makes soft material;
4, soft material is crossed 14 mesh sieves and made wet granular;
5, with wet granular in the dried granule that is dried to water content about 3% about 70 ℃;
6, the disintegrating agent and correctives and the fluidizer that the dried granule of step 5 are added surplus, mixing, tabletting, every heavy 250mg, packing, promptly.
Embodiment 4
Per 1000 difenidol hydrochloride dispersible tablet formulations take by weighing material by following prescription:
Difenidol hydrochloride 25g
Microcrystalline Cellulose 147g
Lactose 75g
Cross-linked pvp 6g
Low-substituted hydroxypropyl cellulose 6g
5% hypromellose aqueous solution 40ml
Magnesium stearate 3g
Orange flavor 2g
The raw material that takes by weighing is prepared difenidol hydrochloride dispersible tablet of the present invention according to the following steps:
1, gets microcrystalline Cellulose 147g, lactose 75g, mixing;
2, get the difenidol hydrochloride of proportional quantity, adopt the equivalent method of progressively increasing to add in step 1 mixture, fully mixing;
3, get 5% hypromellose aqueous solution of proportional quantity, slowly add in step 2 mixture, the limit edged stirs, and makes soft material;
4, soft material is crossed 14 mesh sieves and made wet granular;
5, with wet granular in the dried granule that is dried to water content about 3% about 70 ℃;
6, the dried granule of step 5 is added correctives and fluidizer and disintegrating agent cross-linked pvp, low-substituted hydroxypropyl cellulose, mixing, tabletting, every heavy 250mg, packing, promptly.
Different embodiment disintegration times are measured:
More than 4 embodiment because proportioning is different, its disintegration time is measured, acetonideexample 1 disintegration time is that 7 seconds, embodiment 2 disintegration times are that 5 seconds, embodiment 1 disintegration time are that 11 seconds, embodiment 1 disintegration time are 8 seconds, all 15 seconds with interior complete disintegrate, have good disintegrating property.
The selection of table 1 dissolution medium
| Dissolution medium | Dissolution | ||||||
| 1 | 2 | 3 | 4 | 5 | 6 | On average | |
| Water 0.1mol/L hydrochloric acid | 93.8 95.4 | 98.2 96.5 | 99.9 93.7 | 95.1 99.1 | 99.8 100.2 | 98.9 95.6 | 97.6 96.8 |
Table 2 rotating speed is to the influence of stripping
| Rotating speed (rev/min) | Dissolution | ||||||
| 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods | |
| 50 75 100 | 92.9 97.3 97.4 | 93.0 100.6 101.8 | 92.1 94.5 100.7 | 89.5 102.5 95.6 | 94.3 101.0 102.9 | 90.4 92.5 98.0 | 92.0 98.1 99.4 |
Study on the stability in table 3 dissolution medium
| Time (h) | 0h | 0.5h | 1h | 2h | RSD(％) |
| Peak area | 4531477 | 4596541 | 4588774 | 4598762 |
Table 4 dissolution homogeneity
| Time (min) | Stripping quantity (%) | |||||||
| 1 | 2 | 3 | 4 | 5 | 6 | On average (%) | RSD(％) | |
| 5 10 15 30 45 | 68.9 83.1 89.1 96.6 98.7 | 58.0 78.5 84.3 101.2 104.1 | 73.9 86.4 95.0 105.6 102.7 | 66.0 78.5 85.4 98.5 99.3 | 69.5 81.0 93.1 101.6 104.8 | 45.5 65.5 78.5 98.5 98.7 | 63.6 78.8 87.6 100.4 101.4 | 16.2 9.1 7.0 3.2 2.8 |
Table 5 stripping curve
| Lot number 040919 | Time (min) | Stripping quantity (%) | |||||||
| 1 | 2 | 3 | 4 | 5 | 6 | On average (%) | RSD(％) | ||
| 5 10 15 30 45 | 58.0 80.1 95.6 98.9 100.6 | 49.5 76.8 86.0 92.9 49.5 | 67.2 86.6 94.8 98.5 103.5 | 70.8 78.5 89.3 95.2 101.9 | 58.2 75.3 88.7 94.1 100.0 | 71.8 88.1 96.0 102.1 102.3 | 62.6 80.9 91.7 96.9 101.1 | 14.0 6.5 4.6 3.6 1.8 | |
| 040920 | 5 10 15 30 45 | 62.0 82.2 94.3 98.5 100.2 | 56.6 77.4 88.5 94.8 99.1 | 72.8 83.3 91.8 97.1 100.4 | 72.8 83.3 91.8 97.1 100.4 | 59.5 81.0 91.6 96.4 98.7 | 76.2 92.3 99.8 102.7 103.5 | 65.6 84.1 93.5 98.3 101.1 | 11.8 6.4 4.1 3.0 2.4 |
| 040921 | 5 10 15 30 45 | 53.0 72.2 86.6 93.9 99.6 | 81.0 90.2 97.3 99.6 100.6 | 55.3 70.5 83.1 92.9 98.3 | 55.3 70.5 83.1 92.9 98.3 | 80.4 91.8 97.3 101.6 104.8 | 80.6 92.3 97.1 99.3 99.6 | 71.1 83.7 92.1 97.2 100.4 | 18.6 11.8 6.7 3.6 2.2 |
Claims (10)
1, a kind of difenidol hydrochloride dispersible tablet, it is characterized in that in its dispersible tablet formulation, ingredient comprises principal agent difenidol hydrochloride and adjuvant, contain disintegrating agent in the adjuvant, its percentage by weight consists of: difenidol hydrochloride 10%-50%, adjuvant 50%-90%, disintegrating agent accounts for the 5%-20% of whole ingredient in the adjuvant.
2, difenidol hydrochloride dispersible tablet according to claim 1 is characterized in that described disintegrating agent can be one or more the mixture in cross-linked pvp, low-substituted hydroxypropyl cellulose, the carboxymethyl starch sodium.
3, difenidol hydrochloride dispersible tablet according to claim 1 is characterized in that also comprising in the adjuvant: (1) diluent is that filler, (2) binding agent, (3) correctives, (4) fluidizer are one or more the mixture in the polishing material.
4, difenidol hydrochloride dispersible tablet according to claim 3 is characterized in that diluent can be one or more the mixture in microcrystalline Cellulose, lactose, powdered sugar, starch, dextrin, the pregelatinized Starch; Binding agent can be the aqueous solution of starch slurry (2%-10%), hypromellose (2%-10%) or PVP (2%-10%) or one or more the mixture in the alcoholic solution; Correctives can be one or more the mixture in Herba Menthae essence, flavoring orange essence, the orange flavor; Fluidizer can be one or more the mixture in magnesium stearate, the micropowder silica gel.
5, difenidol hydrochloride dispersible tablet according to claim 3 is characterized in that ingredient comprises in per 1000 tablet preparations:
Difenidol hydrochloride 25g
Adjuvant 25～1975g.
6, difenidol hydrochloride dispersible tablet according to claim 5 is characterized in that the composition proportion scope can be in per 1000 tablet preparations:
Difenidol hydrochloride 25g
Diluent 0～1970g
Disintegrating agent 2.5～400g
Binding agent 0～600ml
Fluidizer 0～40g
Correctives 0～40g
7, difenidol hydrochloride dispersible tablet according to claim 6 is characterized in that the adjunct ingredient ratio range is in per 1000 tablet preparations:
(1) diluent is a filler: 1～1970g, can adopt one or more the mixture in microcrystalline Cellulose, lactose, powdered sugar, starch, dextrin, the pregelatinized Starch;
(2), disintegrating agent: 2.5～400g, can adopt one or more the mixture in cross-linked pvp, low-substituted hydroxypropyl cellulose, the carboxymethyl starch sodium;
(3), binding agent: 5～600ml, can adopt the aqueous solution of 2%-10% starch slurry, 2%-10% hypromellose aqueous solution or alcoholic solution, 2%-10%PVP or one or more the mixture in the alcoholic solution;
(4), correctives: 1～40g, can adopt one or more the mixture in Herba Menthae essence, flavoring orange essence, the orange flavor;
(5), fluidizer is polishing material: 6～40g, can adopt the mixture of a kind of in magnesium stearate, the micropowder silica gel or two kinds.
8, a kind of preparation method of difenidol hydrochloride dispersible tablet is pressed in per 1000 tablet preparations of difenidol hydrochloride dispersible tablet, and the composition proportion scope is:
Difenidol hydrochloride 25g
Diluent 0～1970g
Disintegrating agent 2.5～400g
Binding agent 0～600ml
Fluidizer 0～40g
Correctives 0～40g
Its preparation may further comprise the steps:
(1), get the diluent of proportional quantity, abundant mixing, diluent mixture; Or a part of getting the disintegrating agent of the diluent of proportional quantity and proportional quantity, abundant mixing, the mixture of diluent and disintegrating agent;
(2), get the difenidol hydrochloride of proportional quantity, adopt the equivalent method of progressively increasing to add that mixing gets mixture in the diluent of step 1 gained;
(3), will add disintegrating agent, correctives and the fluidizer that remains in the disintegrating agent of proportional quantity or the step 1 in the mixture of step 2, mixing, tabletting, packing, promptly.
9, the preparation method of difenidol hydrochloride dispersible tablet according to claim 7 is characterized in that further comprising the steps of:
(3-1), the binding agent of getting proportional quantity adds in the mixture of step 2, the limit edged stirs, and makes soft material;
(4), soft material is crossed the 10-30 mesh sieve and made wet granular;
(5), with wet granular in 50-80 ℃ of dried granule that is dried to water content 1%-8%;
(6), dried granule that step 5 is made adds disintegrating agent, correctives and the fluidizer that remains in the disintegrating agent of proportional quantity or the step 1, mixing, tabletting, packing, promptly.
10, according to Claim 8 or the preparation method of 9 described difenidol hydrochloride dispersible tablets, it is characterized in that diluent can be one or more the mixture in microcrystalline Cellulose, lactose, powdered sugar, starch, dextrin, the pregelatinized Starch; Binding agent can be the aqueous solution of 2%-10% starch slurry, 2%-10% hypromellose or 2%-10%PVP or one or more the mixture in the alcoholic solution; Correctives can be one or more the mixture in Herba Menthae essence, flavoring orange essence, the orange flavor; Fluidizer can be one or more the mixture in magnesium stearate, the micropowder silica gel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510103521 CN1935140A (en) | 2005-09-19 | 2005-09-19 | Compound diphenidol hydrochloride dispersible tablet, and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510103521 CN1935140A (en) | 2005-09-19 | 2005-09-19 | Compound diphenidol hydrochloride dispersible tablet, and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1935140A true CN1935140A (en) | 2007-03-28 |
Family
ID=37953004
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510103521 Pending CN1935140A (en) | 2005-09-19 | 2005-09-19 | Compound diphenidol hydrochloride dispersible tablet, and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1935140A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105326803A (en) * | 2015-12-05 | 2016-02-17 | 翔宇药业股份有限公司 | Difenidol hydrochloride tablets for treating motion sickness and preparation method thereof |
| CN107213124A (en) * | 2017-05-04 | 2017-09-29 | 广西大海阳光药业有限公司 | A kind of preparation of suppression therapy motion sickness and preparation method thereof |
| CN108283625A (en) * | 2018-04-26 | 2018-07-17 | 江苏四环生物制药有限公司 | A kind of preparation method of difenidol hydrochloride piece |
| US10188610B2 (en) | 2013-01-16 | 2019-01-29 | Invekra, S.A.P.I. De C.V. | Prolonged-release diphenidol composition |
-
2005
- 2005-09-19 CN CN 200510103521 patent/CN1935140A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10188610B2 (en) | 2013-01-16 | 2019-01-29 | Invekra, S.A.P.I. De C.V. | Prolonged-release diphenidol composition |
| CN105326803A (en) * | 2015-12-05 | 2016-02-17 | 翔宇药业股份有限公司 | Difenidol hydrochloride tablets for treating motion sickness and preparation method thereof |
| CN107213124A (en) * | 2017-05-04 | 2017-09-29 | 广西大海阳光药业有限公司 | A kind of preparation of suppression therapy motion sickness and preparation method thereof |
| CN108283625A (en) * | 2018-04-26 | 2018-07-17 | 江苏四环生物制药有限公司 | A kind of preparation method of difenidol hydrochloride piece |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU692550B2 (en) | Fluoxetine pharmaceutical formulations | |
| CN108653226A (en) | The daily single administration sustained release preparation of Mosapride of pharmacology and clinical effect is provided | |
| CN101984960A (en) | Rizatriptan benzoate capsule and preparation method thereof | |
| CN102512393A (en) | Oral disintegrated tablet containing tolvaptan | |
| CN104940152B (en) | A kind of pharmaceutical composition containing butanedioic acid Solifenacin | |
| CN104546770A (en) | Azilsartan orally-disintegrating tablet and preparation method thereof | |
| CN101455653B (en) | Arginine ibuprofen oral disintegrating tablets and preparation method thereof | |
| CN103520128A (en) | Pramipexole sustained-release tablet, preparation method and application thereof | |
| CN1935140A (en) | Compound diphenidol hydrochloride dispersible tablet, and its preparing method | |
| CN104523628B (en) | It is a kind of can direct powder compression butanedioic acid Solifenacin tablet and preparation method thereof | |
| CN100588400C (en) | Fast disintegrating agent containing paroxetine | |
| CN106038502A (en) | Ramelteon oral disintegrating tablets and preparation method thereof | |
| CN103191077A (en) | Gliclazide tablet and preparation method thereof | |
| CN101836981B (en) | Compound valsartan benzenesulfonic acid amlodipine medicament composition and new preparation method thereof | |
| CN106074681A (en) | A kind of dispersible tablets of Chinese medicine of anti-hepatic fibrosis and preparation method thereof | |
| CN108159008B (en) | Preparation method of valsartan chewable tablet | |
| CN118384117A (en) | Olmesartan medoxomil orally disintegrating tablet and preparation method thereof | |
| CN118477074A (en) | Olmesartan medoxomil amlodipine pharmaceutical composition and preparation method thereof | |
| CN101703481B (en) | Ribavirin lipid microsphere effervescent granules | |
| CN104840436B (en) | Pharmaceutical composition | |
| CN106890146A (en) | A kind of Oseltamivir phosphate dispersible tablet and preparation method thereof | |
| CN114129528A (en) | Novel sildenafil citrate preparation with clinical advantages and preparation process and application thereof | |
| CN103018190B (en) | A kind of pharmaceutical preparation and dissolution determination method thereof | |
| CN104473916A (en) | Medicinal composition of empagliflozin and preparation method thereof | |
| CN114191403B (en) | Kurarinone tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |