CN102218040A - Oral disintegrating tablets of microcrystallites of aripiprazole composition and preparation method thereof - Google Patents
Oral disintegrating tablets of microcrystallites of aripiprazole composition and preparation method thereof Download PDFInfo
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- CN102218040A CN102218040A CN 201010145059 CN201010145059A CN102218040A CN 102218040 A CN102218040 A CN 102218040A CN 201010145059 CN201010145059 CN 201010145059 CN 201010145059 A CN201010145059 A CN 201010145059A CN 102218040 A CN102218040 A CN 102218040A
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Abstract
The invention relates to orally disintegrating tablets of microcrystallites of an aripiprazole composition and a preparation method thereof, and the orally disintegrating tablets mainly compose the microcrystallites of the aripiprazole lactose composition, a filling agent, a disintegrating agent, a flavor correction agent and a lubricating agent, wherein the particle size of the microcrystallites of the aripiprazole lactose composition is less than 30 mu m. The preparation method comprises the following steps: uniformly mixing all components of the aripiprazole orally disintegrating tablets and then directly tabletting or performing wet-granulation tabletting. The microcrystallites obtained by common micronization of the aripiprazole lactose composition are higher in dissolution rate in comparison with those by independent micronization of aripiprazole; simultaneously, the crystal form of the aripiprazole in the microcrystallites of the composition is not transformed and the uniformity of content of the orally disintegrating tablets is higher; and the hardness of the aripiprazole orally disintegrating tablets is 5-8kg, the disintegration time limit is less than 30 seconds, not only the tablets can be prevented from breaking during transportation, but also the tablets are convenient to take.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of oral cavity disintegration tablet that contains Aripiprazole compositions crystallite and preparation method thereof.
Background technology
Schizophrenia is a kind of serious disabling property mental sickness.Its symptom mainly shows as the positive symptom (as vain hope, hallucination, thought disturbance, hostility and suspect) and strange behavior, because the negative symptoms due to the disappearance of regular complex function (as bradykinesia, apathy, poverty of speech etc.) and because the cognitive symptom due to the infringement appears in thinking and inferential capability, emotion symptom (especially depressed) also may appear in the patient who has.
Aripiprazole (Aripiprazole) is an insoluble drug, dissolubility is about 7.8g/L in water, chemical name 7-[4-[4-(2, the 3-Dichlorobenzene base)-and the 1-piperazinyl] butoxy]-3, the 4-dihydro-quinolinone, be carbostyril derivative, its mechanism of action it be unclear that, but thinks at present by to dopamine receptor (D
2) and 5-hydroxytryptamine receptor (5HT
1A) receptor the part agonism and to 5-HT
2AThe antagonism mediation of receptor produces.Aripiprazole is the another novel psychosis behind atypical antipsychotic agents such as risperidone, olanzapine, Quetiapine, the D that it is unique
2And 5HT
1AThe acceptor portion agonist activity reaches 5HT
2AThe antagonism of receptor has been showed and haloperidol, the similar therapeutical effect of risperidone, after this product treatment, body weight change is atomic, few extrapyramidal symptoms (EPS) that takes place, untoward reaction is little and instructions of taking is easy, for schizophrenic's treatment provides a new selection.
Therefore dysphagia is the common adverse effect of antipsychotic drug, and for the psychotic, the shortcoming that conventional tablet is difficult for swallowing can cause patient compliance poor, and required nursing drops into more, in addition cough and choke appears or the food of choking etc. is life-threatening may.
Oral cavity disintegration tablet is a kind of tablet that water can disintegrate that do not need in the oral cavity, when taking, tablet is placed lingual surface, need not use water delivery service, meets after the saliva disintegrate beading rapidly, swallows into stomach with saliva.Oral cavity disintegration tablet is compared with ordinary tablet, can make things convenient for patient's medication, dysphagia person (as: old man, child) especially, patient's medication of water inconvenience under psychotic or the special environment.
Patent document CN1709256A discloses orally disintegrating tablet preparation of a kind of Aripiprazole and preparation method thereof, adopt polyvinylpolypyrrolidone, microcrystalline Cellulose, mannitol, aspartame, micropowder silica gel and magnesium stearate direct compression process to make, all disintegrates in 1 minute.The aripiprazole orally disintegrating tablet that relates in this invention has adopted a large amount of microcrystalline Cellulose and micropowder silica gel, and the use of insoluble adjuvant causes producing sense of discomfort after its disintegrate in the oral cavity; Simultaneously belong to insoluble drug because of Aripiprazole, among the CN1709256A oral cavity disintegration tablet dissolution of gained more former grind medicine Aripiprazole ordinary tablet (trade name: An Lvfan) on the low side, can not embody the fast advantage of oral cavity disintegration tablet stripping.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, oral cavity disintegration tablet of the Aripiprazole compositions crystallite that a kind of disintegrate is rapid, stripping is fast and preparation method thereof is provided.
Characteristics of the present invention are not use a large amount of microcrystalline Cellulose and micropowder silica gel, but the effective ingredient of oral cavity disintegration tablet is made Aripiprazole compositions crystallite with lactose mix homogeneously pulverize at low temperature earlier, and then add other adjuvants and make oral cavity disintegration tablet.
Technical scheme of the present invention is as follows:
A kind of oral cavity disintegration tablet of Aripiprazole compositions crystallite, the mass parts composition is mainly: the filler of 4-15 part Aripiprazole compositions crystallite, 75-85 part, the disintegrating agent of 1-10 part, the correctives of 0-2 part and the lubricant of 0-2 part;
The mass ratio of Aripiprazole and lactose is 1: 1～1: 5 in the described Aripiprazole compositions crystallite, and the volume average particle size of Aripiprazole compositions crystallite is 3-20 μ m, the granularity D90 of 90% particle≤30 μ m.
Described Aripiprazole compositions crystallite is with behind Aripiprazole and the lactose mix homogeneously, adopts 0 ℃ of-10 ℃ of pulverize at low temperature mode to obtain, preferred 0 ℃-5 ℃.
Preferably, the granularity D90 of 90% particle of described Aripiprazole compositions crystallite≤20 μ m.
Preferably, the mass ratio of Aripiprazole and lactose is 1: 2 in the described Aripiprazole compositions crystallite.
Show that after deliberation the lactose consumption is crossed when hanging down in the Aripiprazole compositions crystallite, can not reach solid dispersion effect preferably in micronization process; Increase crushing quantity when consumption is too high, cost improves.
When the compositions crystallite of aripipazole and lactose adopted too high temperature to pulverize, it is brilliant that the main component aripipazole can take place to change, stability decreases; Reducing to when pulverizing below 0 ℃, temperature conditions is comparatively harsh, needs strict control, and to having relatively high expectations of equipment, cost also can increase.
Above-mentioned filler is a water-soluble filler, is selected from lactose, mannitol, microcrystalline Cellulose or the pre-paying starch one or more.
Above-mentioned disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose or the carboxymethyl starch sodium.
Above-mentioned correctives is selected from one or more in aspartame, orange flavor, strawberry essence or the stevioside.
Above-mentioned lubricant is selected from one or more in magnesium stearate, Pulvis Talci, colloidal silica or the micropowder silica gel.
More than used adjuvant be prior art.
Preferably, the aripiprazole orally disintegrating tablet mass parts is composed as follows among the present invention:
7.5 parts in Aripiprazole compositions crystallite, wherein the mass ratio of Aripiprazole and lactose is 1: 2;
15 parts of lactose;
59.4 parts in mannitol;
10 parts of microcrystalline Cellulose;
6 parts of polyvinylpolypyrrolidone;
0.5 part of orange flavor;
0.6 part of aspartame;
1 part of magnesium stearate.
Because Aripiprazole itself is an insoluble drug, the micronization electrostatic interaction is stronger separately, with other adjuvant mixing Yi Jutuan, is difficult for mix homogeneously.Though pulverizing also can reduce particle diameter separately, improve dissolution, effect is poor than the prepared oral cavity disintegration tablet of the common micronization of the compositions of Aripiprazole and lactose.And the granularity (D90) of Aripiprazole compositions crystallite 90% particle is less than 30 μ m, and the granularity of especially preferred 90% particle (D90) is lower than 20 μ m, has guaranteed the quick disintegrate and the stripping of Aripiprazole.
The preparation method of the oral cavity disintegration tablet of above-mentioned Aripiprazole compositions crystallite is optional following a kind of:
A. with behind Aripiprazole compositions crystallite and the water-soluble filler mix homogeneously with other adjuvant mix homogeneously, adopt the direct powder compression tabletting;
B. will prepare with the method for other adjuvant mix homogeneously tablettings again behind Aripiprazole compositions crystallite and the water soluble adjuvant wet granulation.
Wet granulation process described in the above-mentioned preparation method B prepares oral cavity disintegration tablet, and it is formed except that Aripiprazole compositions crystallite and above-mentioned disintegrating agent, filler, correctives, sweeting agent and lubricant, also needs to add the binding agent or the wetting agent of 0.1-5 weight portion; Described binding agent or wetting agent are selected from one or more the mixture in pure water, carboxymethylcellulose sodium solution, hyprolose solution, the povidone solution.
Terminological interpretation:
Wet granulation process: be in drug powder, to add binding agent or wetting agent, powder is coalesced together and prepare particulate method by the crane span structure of binding agent or wetting agent or cementation.
Compared with prior art, the oral cavity disintegration tablet of prepared Aripiprazole compositions crystallite has the following advantages among the present invention:
1. the granularity of Aripiprazole compositions crystallite adopts the mode of pulverize at low temperature to pulverize less than 30 μ m, and the crushing process crystal formation does not change;
2. the common micronization of Aripiprazole compositions has reached the effect of solid dispersion, effectively improves the dissolution rate of tablet.
3. a poly-group phenomenon does not appear in the independent micronization Aripiprazole easier mixing in mixed process of the common micronization of Aripiprazole compositions, and the uniformity of dosage units of prepared oral cavity disintegration tablet is higher.
4. taking convenience, good mouthfeel.The common micronization of Aripiprazole compositions has improved the mouthfeel of oral cavity disintegration tablet effectively than independent micronization Aripiprazole among the present invention, has improved the compliance that the patient takes medicine.
5. the oral cavity disintegration tablet disintegration rate of Aripiprazole compositions crystallite is fast, should be acute better.Gained oral cavity disintegration tablet of the present invention is disintegrate fast in 30 seconds in mouth, makes the rapid stripping of medicine.
The specific embodiment
Further specify the present invention below in conjunction with embodiment, but be not limited thereto.
The lactose particle diameter is preferably smaller or equal to 150 μ m in the Aripiprazole compositions crystallite, and lactose preferably is applicable to lactose such as lactose Flow100, the lactose T80 etc. of direct powder compression in the filler.
Aripiprazole: Qilu Pharmaceutical Co., Ltd.
Micropowder silica gel: German WARKER company produces and sells.
Optimize microcrystalline Cellulose: German JRS company produces and sells.
Orange flavor: Firmenich ﹠ Cie produces and sells.
Low-substituted hydroxypropyl cellulose: prospect company in Huzhou produces and sells.
Strawberry essence: Firmenich ﹠ Cie produces and sells.
The oral cavity disintegration tablet mass parts of embodiment 1. Aripiprazole compositions crystallites consists of:
7.5 parts in Aripiprazole compositions crystallite (2.5 parts of Aripiprazole+5 part lactose)
15 parts of lactose (filler)
59.4 parts in mannitol (filler)
Optimize 10 parts of microcrystalline Cellulose (filler)
6 parts of polyvinylpolypyrrolidone (disintegrating agent)
0.5 part of orange flavor (correctives)
0.6 part of aspartame (correctives)
1.0 parts of magnesium stearate (lubricant);
Preparation method:
Aripiprazole compositions crystallite and the lactose mix homogeneously of crossing 40 mesh sieves are made mixture A; Mannitol, optimize microcrystalline Cellulose, polyvinylpolypyrrolidone, orange flavor, aspartame and cross 40 mesh sieves respectively after mix homogeneously make mixture B, mixture A and mixture B equivalent are progressively increased behind the method mix homogeneously, add the magnesium stearate mixing after tabletting promptly.
The oral cavity disintegration tablet mass parts of embodiment 2. Aripiprazole compositions crystallites consists of:
Aripiprazole compositions crystallite
(5 parts of Aripiprazole+5 part lactose) 10 parts
72.9 parts in mannitol (filler)
5 parts of microcrystalline Cellulose (filler)
6 parts of low-substituted hydroxypropyl celluloses (disintegrating agent)
3 parts of cross-linking sodium carboxymethyl celluloses (disintegrating agent)
0.5 part of micropowder silica gel (lubricant)
0.5 part of strawberry essence (correctives)
0.6 part of aspartame (correctives)
1.5 parts of magnesium stearate (lubricant);
Preparation method:
Aripiprazole compositions crystallite and the mannitol mix homogeneously of crossing 40 mesh sieves are made mixture A; Mix homogeneously made mixture B after microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, strawberry essence, aspartame were crossed 40 mesh sieves respectively, mixture A and mixture B equivalent are progressively increased behind the method mix homogeneously, add the magnesium stearate mixing after tabletting promptly.
Embodiment 3. Aripiprazole compositions crystallite oral cavity disintegration tablet mass parts consist of:
Aripiprazole compositions crystallite
(2 parts of Aripiprazole+2 part lactose) 4 parts
75 parts in mannitol (filler)
Optimize 10 parts of microcrystalline Cellulose (filler)
8 parts of polyvinylpolypyrrolidone (disintegrating agent)
1.5 parts of orange flavors (correctives)
0.5 part of aspartame (correctives)
0.5 part of micropowder silica gel (lubricant)
0.5 part of magnesium stearate (lubricant);
Preparation method:
Aripiprazole compositions crystallite and the mannitol mix homogeneously of crossing 40 mesh sieves are made mixture A; Mix homogeneously makes mixture B after optimizing microcrystalline Cellulose, polyvinylpolypyrrolidone, orange flavor, aspartame and crossing 40 mesh sieves respectively, and mixture A and mixture B equivalent are progressively increased behind the method mix homogeneously, add micropowder silica gel, magnesium stearate mixing after tabletting promptly.
The oral cavity disintegration tablet of embodiment 4. Aripiprazole compositions crystallites consists of:
Aripiprazole compositions crystallite
(2.5 parts of Aripiprazole+12.5 part lactose) 15 parts
15 parts of lactose (filler)
53 parts in mannitol (filler)
Optimize 10 parts of microcrystalline Cellulose (filler)
6 parts of polyvinylpolypyrrolidone (disintegrating agent)
1.0 parts of magnesium stearate (lubricant);
Preparation method:
Add 5 mass parts pure water system soft materials behind the lactose mix homogeneously with Aripiprazole compositions crystallite and mistake 100 mesh sieves, crossing 20 mesh sieves granulates, in 55 ℃ of dryings 3 hours to moisture below 2%, making granule crosses 40 mesh sieves and obtains mixture A, mix homogeneously obtained mixture B after mannitol, optimization microcrystalline Cellulose, polyvinylpolypyrrolidone were crossed 40 mesh sieves respectively, with mixture A and the mixture B equivalent mix homogeneously that progressively increases, add the magnesium stearate mixing, tabletting is promptly.
Embodiment 5. Aripiprazole compositions crystallite oral cavity disintegration tablet mass parts consist of:
Aripiprazole compositions crystallite
(3.5 parts of Aripiprazole+10.5 part lactose) 14 parts
39.5 parts in mannitol (filler)
26.5 parts of lactose (filler)
11.5 parts of microcrystalline Cellulose (filler)
6 parts of polyvinylpolypyrrolidone (disintegrating agent)
0.5 part of colloidal silica (lubricant)
0.5 part of strawberry essence (correctives)
0.5 part of aspartame (correctives)
1.0 parts of magnesium stearate (lubricant);
Preparation method:
Add 3 mass parts pure water system soft materials behind the lactose mix homogeneously with Aripiprazole compositions crystallite and mistake 100 mesh sieves, crossing 20 mesh sieves granulates, in 55 ℃ of dryings 3 hours to moisture below 2%, making granule crosses 40 mesh sieves and obtains mixture A, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, colloidal silica, strawberry essence, aspartame are crossed 40 sieve back mix homogeneously respectively and are obtained mixture B, with mixture A and the mixture B equivalent mix homogeneously that progressively increases, add the magnesium stearate mixing, tabletting is promptly.
Embodiment 6. Aripiprazole compositions crystallite oral cavity disintegration tablet mass parts consist of:
Aripiprazole compositions crystallite
(7 parts of Aripiprazole+7 part lactose) 14 parts
50 parts in mannitol (filler)
25 parts of lactose (filler)
5 parts of low-substituted hydroxypropyl celluloses (disintegrating agent)
4 parts of cross-linking sodium carboxymethyl celluloses (disintegrating agent)
0.5 part of orange flavor (correctives)
0.5 part of aspartame (correctives)
1.0 parts of magnesium stearate (lubricant);
Add 3 mass parts povidone solution system soft materials behind the lactose mix homogeneously with Aripiprazole compositions crystallite and mistake 100 mesh sieves, crossing 20 mesh sieves granulates, in 55 ℃ of dryings 3 hours to moisture below 2%, making granule crosses 40 mesh sieves and obtains mixture A, mix homogeneously obtained mixture B after mannitol, lactose, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, orange flavor, aspartame were crossed 40 mesh sieves respectively, with mixture A and mixture B mix homogeneously, add the magnesium stearate mixing, tabletting promptly.
Embodiment 7. Aripiprazole compositions crystallite oral cavity disintegration tablet mass parts consist of:
Aripiprazole compositions crystallite
(2 parts of Aripiprazole+4 part lactose) 6 parts
72 parts in mannitol (filler)
Optimize 12 parts of microcrystalline Cellulose (filler)
8 parts of polyvinylpolypyrrolidone (disintegrating agent)
1.0 parts of orange flavors (correctives)
1.0 parts of aspartames (correctives)
Preparation method:
Aripiprazole compositions crystallite and the mannitol mix homogeneously of crossing 40 mesh sieves are made mixture A; Mix homogeneously makes mixture B after optimizing microcrystalline Cellulose, polyvinylpolypyrrolidone, orange flavor, aspartame and crossing 40 mesh sieves respectively, and mixture A and mixture B equivalent are progressively increased behind the method mix homogeneously tabletting promptly.
Embodiment 8 Aripiprazole compositions crystallite oral cavity disintegration tablet dissolutions and experiment disintegration
Experimental technique and test instrunment are as follows among the embodiment:
A, hardness measurement instrument: YD-1 tablet hardness tester (Tianjin state inscription medical equipment company limited)
Get 10 of aripiprazole orally disintegrating tablets (n=10), measure tablet hardness with YD-1 tablet hardness tester respectively.
B, disintegration time mensuration adopt static disintegrate method.Get 1 of aripiprazole orally disintegrating tablet, put in the 10ml test tube (the test tube internal diameter is 13mm), in vitro fill 2ml water, water temperature is 37 ℃, and tablet should disintegrate in 1 minute, be dispersed in the water.Pour out and sieve, each water 2ml, wash test tube and screen cloth at twice, can be all by the screen cloth of aperture less than 710um.Check 6 (n=6) as stated above, should be up to specification.
C, friability are measured, and test according to Chinese Pharmacopoeia version appendix in 2005 X G tablet friability inspection technique.
D, stripping curve measure, and the stripping curve assay method of the aripiprazole orally disintegrating tablet of announcing according to FDA carries out, and is specially: (1) dissolution medium: pH4.0 acetate buffer solution; 1000ml; (2) slurry method, rotating speed: 75 commentaries on classics/min; (3) detect wavelength: 249nm; 10,20,30,45min (4) sampling time point:.
Patent CN1709256A, " orally disintegrating tablet preparation of Aripiprazole and preparation method thereof " discloses following prescription:
Percentage composition
Aripiprazole 4.15
Polyvinylpolypyrrolidone 5.00
Microcrystalline Cellulose 29.90
Mannitol 55.65
Aspartame 0.33
Micropowder silica gel 2.49
Magnesium stearate 1.0;
Use the optimum prescription (experimental example 3) of preparation of the present invention and above-mentioned patent CN1709256A to carry out the comparison of each time point stripping percentage rate and disintegration etc., the result is as shown in table 1:
The prescription dissolution of table 1 embodiment of the invention and Comparative Examples CN1709256A and disintegration contrast and experiment
Through finding that relatively the oral cavity disintegration tablet dissolution rate of Aripiprazole compositions crystallite of the present invention is significantly write out a prescription (experimental example 3) faster than the optimum of patent application CN1709256A, and compares with the stripping curve of original medicine ordinary tablet, and is also very fast.Simultaneously in higher hardness range (5-8kg), lower than the disintegration of the optimum prescription (experimental example 3) of patent application CN1709256A, friability is qualified.
Embodiment 9 Aripiprazole compositions crystallite oral cavity disintegration tablet process crystal formation research experiments
Use the orally disintegrating tablet preparation of the embodiment of the invention 1 to carry out process crystal formation research experiment, the results are shown in Table 2:
The orally disintegrating tablet preparation process crystal formation research experiment result of table 2 embodiment of the invention 1
| Embodiment 1 sample | Characteristic absorption peak |
| Blank adjuvant | Do not have |
| Aripiprazole compositions crystallite | 1677cm -1 |
| Behind the tabletting | 1677cm -1 |
The result shows that it is brilliant that oral cavity disintegration tablet of the present invention does not change in being prepared into the process of preparation, the crystal form with aripipazole compositions crystallite behind the tabletting is consistent, has good stability.
Embodiment 10 Aripiprazole compositions crystallite oral cavity disintegration tablet stability experiments
Use the orally disintegrating tablet preparation of the embodiment of the invention 1 to carry out accelerated tests, the results are shown in Table 3:
The oral cavity disintegration tablet accelerated test result of table 3 embodiment of the invention 1
Aripiprazole orally disintegrating tablet accelerated tests result among the present invention shows, oral cavity disintegration tablet accelerated tests of the present invention 6 months, steady quality.
Claims (10)
1. the oral cavity disintegration tablet of an Aripiprazole compositions crystallite, mass parts are formed and are mainly the filler of 4-15 part Aripiprazole compositions crystallite, 75-85 part, the disintegrating agent of 1-10 part, the correctives of 0-2 part and the lubricant of 0-2 part;
The mass ratio of Aripiprazole and lactose is 1: 1～1: 5 in the described Aripiprazole compositions crystallite, and the preferred mass ratio is 1: 2; The volume average particle size of Aripiprazole compositions crystallite is at 5-15 μ m, the granularity D90 of 90% particle≤30 μ m.
2. the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 1, it is characterized in that described Aripiprazole compositions crystallite is with behind Aripiprazole and the lactose mix homogeneously, adopt 0 ℃ of-10 ℃ of pulverize at low temperature mode to obtain, preferred 0 ℃ of-5 ℃ of pulverize at low temperature.
3. the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 1 is characterized in that the granularity D90≤20 μ m of 90% particle of described Aripiprazole compositions crystallite.
4. the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 1 is characterized in that filler is selected from one or more in lactose, mannitol, microcrystalline Cellulose or the pre-paying starch.
5. the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 1 is characterized in that disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose or the carboxymethyl starch sodium.
6. the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 1 is characterized in that correctives is selected from one or more in aspartame, orange flavor, strawberry essence or the stevioside.
7. the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 1 is characterized in that lubricant is selected from one or more in magnesium stearate, Pulvis Talci, colloidal silica or the micropowder silica gel.
8. the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 1 is characterized in that mass parts is composed as follows:
7.5 parts in Aripiprazole compositions crystallite, wherein the part by weight of Aripiprazole and lactose is 1: 2;
15 parts of lactose;
59.4 parts in mannitol;
10 parts of microcrystalline Cellulose;
6 parts of polyvinylpolypyrrolidone;
0.5 part of orange flavor;
0.6 part of aspartame;
1 part of magnesium stearate.
9. the preparation method of the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 1 is characterized in that optional following a kind of:
A. with behind Aripiprazole compositions crystallite and the water-soluble filler mix homogeneously with other adjuvant mix homogeneously, adopt the direct powder compression tabletting;
B. will prepare with the method for other adjuvant mix homogeneously tablettings again behind Aripiprazole compositions crystallite and the water soluble adjuvant wet granulation.
10. the preparation method of the oral cavity disintegration tablet of Aripiprazole compositions crystallite as claimed in claim 9, it is characterized in that: the wet granulation process described in the preparation method B prepares oral cavity disintegration tablet, it is formed except that Aripiprazole compositions crystallite and above-mentioned disintegrating agent, filler, correctives, sweeting agent and lubricant, also adds 0.1-5 mass parts binding agent or wetting agent; Described binding agent or wetting agent are one or more the mixture in pure water, carboxymethylcellulose sodium solution, hyprolose solution, the povidone solution.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310236163.5A CN103284968B (en) | 2010-04-13 | 2010-04-13 | Oral cavity disintegration tablet of a kind of aripiprazole composition microcrystalline and preparation method thereof |
| CN 201010145059 CN102218040A (en) | 2010-04-13 | 2010-04-13 | Oral disintegrating tablets of microcrystallites of aripiprazole composition and preparation method thereof |
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| CN 201010145059 CN102218040A (en) | 2010-04-13 | 2010-04-13 | Oral disintegrating tablets of microcrystallites of aripiprazole composition and preparation method thereof |
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| CN201310236163.5A Division CN103284968B (en) | 2010-04-13 | 2010-04-13 | Oral cavity disintegration tablet of a kind of aripiprazole composition microcrystalline and preparation method thereof |
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| CN201310236163.5A Active CN103284968B (en) | 2010-04-13 | 2010-04-13 | Oral cavity disintegration tablet of a kind of aripiprazole composition microcrystalline and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103536568A (en) * | 2012-07-12 | 2014-01-29 | 成都康弘药业集团股份有限公司 | Orally disintegrating tablets containing lurasidone and preparation method thereof |
| CN112315922A (en) * | 2020-10-12 | 2021-02-05 | 安徽金太阳生化药业有限公司 | Preparation method of cimetidine tablets |
| CN114224855A (en) * | 2021-12-01 | 2022-03-25 | 北京悦康科创医药科技股份有限公司 | Doxazosin mesylate buccal tablet and preparation method thereof |
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| CN104622824A (en) * | 2015-01-27 | 2015-05-20 | 美吉斯制药（厦门）有限公司 | Aripiprazole orally disintegrating tablet and preparation method thereof |
| CN106913548A (en) * | 2015-12-28 | 2017-07-04 | 药源药物化学（上海）有限公司 | A kind of Aripiprazole oral disintegrating tablet and preparation method thereof |
| CN108078941A (en) * | 2018-02-07 | 2018-05-29 | 瑞阳制药有限公司 | aripiprazole oral disintegrating tablet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103536568A (en) * | 2012-07-12 | 2014-01-29 | 成都康弘药业集团股份有限公司 | Orally disintegrating tablets containing lurasidone and preparation method thereof |
| CN106074414A (en) * | 2012-07-12 | 2016-11-09 | 成都康弘药业集团股份有限公司 | A kind of oral cavity disintegration tablet containing Lurasidone and preparation method thereof |
| CN103536568B (en) * | 2012-07-12 | 2016-12-07 | 成都康弘药业集团股份有限公司 | A kind of oral cavity disintegration tablet containing Lurasidone and preparation method thereof |
| CN106074414B (en) * | 2012-07-12 | 2019-01-18 | 成都康弘药业集团股份有限公司 | A kind of oral disnitegration tablet and preparation method thereof containing Lurasidone |
| CN112315922A (en) * | 2020-10-12 | 2021-02-05 | 安徽金太阳生化药业有限公司 | Preparation method of cimetidine tablets |
| CN112315922B (en) * | 2020-10-12 | 2023-07-04 | 安徽金太阳生化药业有限公司 | Preparation method of cimetidine tablet |
| CN114224855A (en) * | 2021-12-01 | 2022-03-25 | 北京悦康科创医药科技股份有限公司 | Doxazosin mesylate buccal tablet and preparation method thereof |
| CN114224855B (en) * | 2021-12-01 | 2023-11-28 | 北京悦康科创医药科技股份有限公司 | Doxazosin mesylate buccal tablet and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103284968B (en) | 2015-11-18 |
| CN103284968A (en) | 2013-09-11 |
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Application publication date: 20111019 |