CN101889986A - Flunarizine orally disintegrating tablet and preparation method thereof - Google Patents
Flunarizine orally disintegrating tablet and preparation method thereof Download PDFInfo
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- CN101889986A CN101889986A CN2009100518128A CN200910051812A CN101889986A CN 101889986 A CN101889986 A CN 101889986A CN 2009100518128 A CN2009100518128 A CN 2009100518128A CN 200910051812 A CN200910051812 A CN 200910051812A CN 101889986 A CN101889986 A CN 101889986A
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Abstract
The invention provides a flunarizine orally disintegrating tablet, which consists of flunarizine and pharmaceutic adjuvant, wherein the pharmaceutic adjuvant comprises a filler, a disintegrating agent, a flavoring agent, an effervescing agent, a lubricating agent and the like. Compared with the disintegrating time limit of a common flunarizine tablet, the flunarizine orally disintegrating tablet has the characteristic of quick response. Mouthfeel observation experiments show that the flunarizine orally disintegrating tablet has good mouthfeel and is easy to be accepted by the patient. In vitro dissolution experiment results show that the bioavailability of the flunarizine orally disintegrating tablet is obviously higher than that of the common flunarizine tablet. The flunarizine orally disintegrating tablet can be quickly dispersed without water or swallow action, and has the advantages of no sand feel, good patient compliance, quick response, and high bioavailability; meanwhile, the preparation process is simple and suitable for industrial production.
Description
Technical field
The present invention relates to pharmaceutical preparation, be specifically related to the oral cavity disintegration tablet dosage form, relate in particular to a kind of Flunarizine orally disintegrating tablet and preparation method thereof.
Background technology
Flunarizine, two (4-fluorophenyl) methyl of chemistry (E)-1-[by name]-4-2 (2-acrylic-3-phenyl)-piperazine, be a kind of calcium channel blocker medicine.The main pharmacological of flunarizine is: (1) alleviating vascular spasm, and the persistence vasospasm that vasoconstrictor substance is caused has persistent inhibitory action, and is especially obvious to basilar artery and internal carotid artery, and its effect is stronger 15 times than cinnarizine; (2) vestibule inhibitory action can increase cochlea small artery blood flow, improves the vestibular apparatus circulation; (3) antiepileptic action, the pathologic calcium overload of neurocyte capable of blocking and prevent the paroxysmal depolarization, the cell discharge, thus avoid epilepsy; (4) protection cardiac muscle obviously alleviates the ischemic myocardial infringement; (5) improve renal function, can be used for chronic renal failure; In addition, flunarizine also has the antihistaminic effect.Flunarizine is mainly used in brain blood clinically for not enough, the vertebral artery ischemia, and cerebral thrombosis and tinnitus, brain are swooned, and also can be used for migraine prevention and epilepsy auxiliary treatment simultaneously.Because flunarizine soluble,very slightly in water, its dissolution rate in stomach is slower, is unfavorable for the absorption of medicine, and bioavailability is low.
Oral cavity disintegration tablet is a kind of new oral dosage form that emerges rapidly in the medicament field in recent years, compare with conventional tablet, this dosage form need not water and also need not to chew, medicine places on the tongue, after meeting the rapid disintegrate of saliva, borrow swallowing act to go into the stomach onset, also can place the Sublingual, medicine passes through the mucosa absorption onset after the disintegrate rapidly.This dosage form is particularly suitable for some old peoples, child, swallow inconvenient patient or the hydropenia condition of going out under patient take, and have the characteristics rapid-action, that bioavailability is high.
Oral cavity disintegration tablet of having reported and preparation method mainly contain (1) and adopt the lyophilization preparation method, behind medicine and adjuvant mixed dissolution, are placed in the particular mold hole, after the lyophilization molding, again through seal package.This oral cavity disintegration tablet has disintegrative preferably, but the oral cavity disintegration tablet hardness extreme difference of this prepared, slice, thin piece is easily broken when getting it filled, the easy moisture absorption of tablet, and preparation technology is loaded down with trivial details, and is subjected to the constraint of manufacturing equipment, has limited the development of this dosage form.(2) medicine is compressed in the slice, thin piece that contains easy sublimate,, but flings to sublimate, obtain a kind of high hole sheet again with the baking oven internal heating of this slice, thin piece in uniform temperature.This oral cavity disintegration tablet also has good suction disintegrate or dissolubility in the oral cavity, and disintegration time is also very short, but in the sheet of this method preparation easily sublimate may in sheet, have residual, unfavorable to human body, and the intensity of slice, thin piece is also not ideal enough.(3) be the oral cavity disintegration tablet that contains effervescent.Contain NaHCO in this slice, thin piece
3Or Na
2CO
3And organic acid, meet saliva of buccal cavity and promptly produce CO
2, cause the rapid disintegrate of slice, thin piece.But this oral cavity disintegration tablet that contains effervescent is in use, because of produce a large amount of bubbles make the oral cavity do not feel well should, the patient is difficult for accepting.
Summary of the invention
Technical problem to be solved by this invention is to overcome above-mentioned weak point, and a kind of preparation technology of research design is simple, taking convenience,, Flunarizine orally disintegrating tablet preparation that bioavailability high rapid-action to indication and preparation method thereof.
The invention provides a kind of Flunarizine orally disintegrating tablet preparation, form by flunarizine and pharmaceutic adjuvant as active component.Pharmaceutic adjuvant comprises filler, disintegrating agent, correctives, effervescent, lubricant etc.
The constituent of Flunarizine orally disintegrating tablet of the present invention is by following quality proportioning, and every is:
Flunarizine 2mg-20mg
Filler 50mg-150mg
Disintegrating agent 20mg-80mg
Correctives 0-20mg
Acidic flavoring agent 0-20mg
Lubricant 1mg-5mg
Flunarizine orally disintegrating tablet of the present invention, every contains flunarizine 2-20mg, preferably 2.5mg, 5mg and 10mg.
Described filler is one or more the mixture in microcrystalline Cellulose, mannitol, sucrose, sorbitol, lactose, xylitol, trehalose, dextrin, starch or the calcium sulfate.
Described disintegrating agent is one or more a mixture of low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, carboxymethyl starch sodium or cross-linking sodium carboxymethyl cellulose.
Described correctives is one or more the mixture in stevioside, aspartame, alpha-lactose, maltose, saccharin sodium, protein sugar, sucrose or the Mentholum.
Described acidic flavoring agent is a tartaric acid.
Described lubricant is selected from one or more the mixture in magnesium stearate, Stepanol MG, micropowder silica gel, Pulvis Talci, the Polyethylene Glycol etc.
Another object of the present invention provides the preparation method of above-mentioned Flunarizine orally disintegrating tablet preparation, and this method comprises the following steps:
(1) get flunarizine and other adjuvants, cross 60 mesh sieves, standby;
(2) with adjuvant mix homogeneously such as flunarizine and filler, disintegrating agent, acidic flavoring agent, correctives, lubricants;
(3) with above-mentioned mixed powder tabletting; Packing gets final product after the assay was approved.
Flunarizine orally disintegrating tablet provided by the invention is compared with general oral cavity disintegration tablet, difference has been to select to carry out the adjuvant of direct compression, as 100 order lactose, vertical compression type mannitol, pH102 type microcrystalline Cellulose etc., processes such as granulation, drying in preparation method, have been removed from, effectively reduce production stage, reduced production cost.Simultaneously, do not contain NaHCO in the Flunarizine orally disintegrating tablet prescription provided by the invention
3Or Na
2CO
3, the patient takes Shi Buhui and produces CO
2Gas has improved patient's medication compliance.
The present invention is by contrasting disintegration with common flunarizine sheet, and this product has rapid-action characteristics.The mouthfeel viewing test illustrates that this Flunarizine orally disintegrating tablet mouthfeel is better, is easy to be accepted by the patient.The dissolution in vitro result of the test shows that the bioavailability of Flunarizine orally disintegrating tablet of the present invention will be apparently higher than the flunarizine ordinary tablet.Flunarizine orally disintegrating tablet of the present invention need not water or swallowing act and just can disperse rapidly, and do not have grittiness, and patient compliance is good, and is rapid-action, the bioavailability height, and preparation technology is simple simultaneously, is fit to suitability for industrialized production.
The specific embodiment
Following example will the present invention is further elaborated, but do not limit content involved in the present invention in any form.
Embodiment 1: Flunarizine orally disintegrating tablet preparation 1
Prescription:
Flunarizine 2.5g
Sorbitol 100g
Low-substituted hydroxypropyl cellulose 2.5g
Tartaric acid 1g
Magnesium stearate 2g
Make 1000
Preparation process: flunarizine, sorbitol, low-substituted hydroxypropyl cellulose, the tartaric acid with recipe quantity sieves mix homogeneously respectively earlier; Add the recipe quantity magnesium stearate again in above-mentioned mixed powder, mix homogeneously, direct compression are promptly.
Embodiment 2: Flunarizine orally disintegrating tablet preparation 2
Prescription:
Flunarizine 5g
Microcrystalline Cellulose 80g
Lactose 50g
Carboxymethyl starch sodium 4g
Tartaric acid 2g
Micropowder silica gel 2g
Magnesium stearate 2g
Make 1000
Preparation process: flunarizine, microcrystalline Cellulose, lactose, carboxymethyl starch sodium, the tartaric acid with recipe quantity sieves mix homogeneously respectively earlier; Add recipe quantity micropowder silica gel, magnesium stearate again in above-mentioned mixed powder, mix homogeneously, direct compression are promptly.
Embodiment 3: Flunarizine orally disintegrating tablet preparation 3
Prescription:
Flunarizine 5g
Mannitol 200SD 80g
Lactose 50g
Polyvinylpolypyrrolidone 10g
Tartaric acid 4g
Aspartame 1g
Micropowder silica gel 2g
Magnesium stearate 2g
Make 1000
Preparation process: flunarizine, mannitol 200SD, lactose, polyvinylpolypyrrolidone, aspartame, the tartaric acid with recipe quantity sieves mix homogeneously respectively earlier; Add recipe quantity micropowder silica gel, magnesium stearate again in above-mentioned mixed powder, mix homogeneously, direct compression are promptly.
Embodiment 4: Flunarizine orally disintegrating tablet and contrast disintegration of common flunarizine sheet
1) common flunarizine sheet is checked disintegration
Test method: according to the requirement of 2005 editions 2 ones of Chinese Pharmacopoeias, get 6 of flunarizine sheets, place disintegration tester, observe whole disintegration of tablet required times.
Result of the test sees Table 1
All the disintegration of tablet time is as follows:
| Sheet 1 | Sheet 2 | Sheet 3 | Sheet 4 | Sheet 5 | Sheet 6 | |
| Disintegration time | 9 minutes 31 seconds | 8 minutes 55 seconds | 9 minutes 12 seconds | 8 minutes 34 seconds | 9 minutes 23 seconds | 8 minutes 57 seconds |
2) Flunarizine orally disintegrating tablet is checked disintegration
Be the main quality control index of oral cavity disintegration tablet and conventional tablet difference disintegration, adopts three kinds of methods to studying the disintegration of flunarizine.
A. volunteer oral's test method(s)
Get 6 of this product, divide and do not invite six volunteer's tests, put into the oral cavity timing from this product, to feeling that the complete disintegrate of tablet is diffusing, no grittiness is ended, and is the disintegration time of this product.The results are shown in Table 2 (wherein sheet 1 is embodiment 1 sample, and sheet 5,6 is embodiment 2 samples, and sheet 2,3,4 is embodiment 3 samples)
The oral laboratory method working sample of table 2 result's disintegration
B. with reference to pharmacopeia inspection technique disintegration
Get 6 of this product, do not open under the condition of falling at hanging basket and test according to inspection technique disintegration (two appendix X of Chinese Pharmacopoeia version in 2005 A), treat that whole disintegrates are loose after, flip hanging basket, make it to pass through screen cloth.The results are shown in Table 3.
The oral laboratory method working sample of table 3 result's disintegration
C. a small amount of solvent test method(s)
According to there being the critical point to collapse the method requirement in time limit, for reasonable observation this product disintegration phenomenon, reduce operate miss, we adopt 2 to add the mensuration that 4ml water carries out disintegration, operation for convenience, use the 10ml small beaker to be container, through test of many times, this method can more objectively reflect the disintegrate situation of this product.Originally answering similar on request is static method, but owing to adopted high performance super-disintegrant in the oral cavity disintegration tablet, being characterized in meeting water can expand rapidly or swelling, tablet can absorb a large amount of moisture content when meeting water immediately, and may produce the phenomenon that sticks on the chamber wall, so, allow slight jolting beaker, prevention tablet bonding container carrying out this product when checking disintegration.
Get 2 of this product, put in the 10ml beaker that fills 37 ℃ ± 1 ℃ of 4ml water, slight jolting.Carry out disintegration and check, the results are shown in Table 4.(wherein sheet 1,2 is embodiment 1 sample, and sheet 3,4 is that embodiment 2 samples, sheet 5,6 are embodiment 3 samples)
Table 4 a small amount of solvent test method determination sample result's disintegration
From the result of above-mentioned three kinds of methods as seen, external disintegration time mensuration result can reflect that substantially this product is in the intraoral disintegration situation.According to the Flunarizine orally disintegrating tablet of this law preparation, the disintegration time in the oral cavity is substantially in 30 seconds, far below the disintegration time of flunarizine ordinary tablet.Therefore, this product has rapid-action characteristics.
Embodiment 5: the mouthfeel of Flunarizine orally disintegrating tablet is observed
Because an important indicator of oral cavity disintegration tablet is that mouthfeel will be got well, and is easy to be accepted by the patient, therefore, we have observed the mouthfeel situation of Flunarizine orally disintegrating tablet in experimenter's mouth.(tablet can not be swallowed down behind tester's Orally disintegrating, must tell immediately, and gargle 3-4 time with clear water, and to prevent medicine residual in the oral cavity, each tester can only test 1 every day) the results are shown in Table 5.(experimenter 1,2 is embodiment 1 sample, and experimenter 3,4 is embodiment 2 samples, and experimenter 5,6 is embodiment 3 samples)
The mouthfeel of table 5 Flunarizine orally disintegrating tablet is observed
Illustrate that this Flunarizine orally disintegrating tablet mouthfeel is better, be easy to be accepted by the patient.
Embodiment 6: the dissolution in vitro of Flunarizine orally disintegrating tablet is observed
1) common flunarizine sheet is checked disintegration
Test method: get 6 of flunarizine sheets, requirement according to 2005 editions 2 ones of Chinese Pharmacopoeias, with the hydrochloric acid solution is dissolution medium, and rotating speed is 100 commentaries on classics, operation in accordance with the law, during respectively at 5,10,15,20,30 minutes, get solution 10ml (and replenishing the 10ml dissolution medium immediately), filter, need filtrate as need testing solution, press the method for assay, measure every dissolution.
Result of the test sees Table 6
The dissolution test of table 6 flunarizine ordinary tablet
2) Flunarizine orally disintegrating tablet is checked disintegration
Test method: get 6 of embodiment 1 Flunarizine orally disintegrating tablets, requirement according to 2005 editions 2 ones of Chinese Pharmacopoeias, with the hydrochloric acid solution is dissolution medium, and rotating speed is 100 commentaries on classics, operation in accordance with the law, during respectively at 5,10,15,20,30 minutes, get solution 10ml (and replenishing the 10ml dissolution medium immediately), filter, need filtrate as need testing solution, press the method for assay, measure every dissolution.
Result of the test sees Table 7
The dissolution test of table 7 Flunarizine orally disintegrating tablet
This shows, stripping is complete in the time of 10 minutes for Flunarizine orally disintegrating tablet, and the flunarizine ordinary tablet just reaches 80% limit of pharmacopeia regulation about 20 minutes, therefore we reach a conclusion, will be apparently higher than the flunarizine ordinary tablet according to the bioavailability of the Flunarizine orally disintegrating tablet of this law preparation.
Claims (10)
1. Flunarizine orally disintegrating tablet is characterized in that described oral cavity disintegration tablet is made up of flunarizine and pharmaceutic adjuvant as active component, and its constituent is by following quality proportioning, and every is:
Flunarizine 2mg-20mg
Filler 50mg-150mg
Disintegrating agent 20mg-80mg
Correctives 0-20mg
Acidic flavoring agent 0-20mg
Lubricant 1mg-5mg.
2. Flunarizine orally disintegrating tablet according to claim 1 is characterized in that, every contains flunarizine 2-20mg.
3. Flunarizine orally disintegrating tablet according to claim 1 is characterized in that, every contains flunarizine 2.5mg or 5mg.
4. Flunarizine orally disintegrating tablet according to claim 1 is characterized in that, every contains flunarizine 10mg.
5. Flunarizine orally disintegrating tablet according to claim 1 is characterized in that, described filler is one or more the mixture in microcrystalline Cellulose, mannitol, sucrose, sorbitol, lactose, xylitol, trehalose, dextrin, starch or the calcium sulfate.
6. Flunarizine orally disintegrating tablet according to claim 1 is characterized in that, described disintegrating agent is one or more a mixture of low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, carboxymethyl starch sodium or cross-linking sodium carboxymethyl cellulose.
7. Flunarizine orally disintegrating tablet according to claim 1 is characterized in that, described correctives is one or more the mixture in stevioside, aspartame, alpha-lactose, maltose, saccharin sodium, protein sugar, sucrose or the Mentholum.
8. Flunarizine orally disintegrating tablet according to claim 1 is characterized in that, described acidic flavoring agent is a tartaric acid.
9. Flunarizine orally disintegrating tablet according to claim 1 is characterized in that, described lubricant is one or more the mixture in magnesium stearate, Stepanol MG, micropowder silica gel, Pulvis Talci or the Polyethylene Glycol.
10. as the preparation method of each described Flunarizine orally disintegrating tablet of right 1-9, it is characterized in that this method comprises the following steps:
(1) get flunarizine and pharmaceutic adjuvant respectively, sieve, standby;
(2) flunarizine and filler, disintegrating agent, acidic flavoring agent, correctives and mix lubricant is even;
(3) with above-mentioned mixed powder tabletting; Packing gets final product after the assay was approved.
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| CN2009100518128A CN101889986A (en) | 2009-05-22 | 2009-05-22 | Flunarizine orally disintegrating tablet and preparation method thereof |
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|---|---|---|---|
| CN2009100518128A CN101889986A (en) | 2009-05-22 | 2009-05-22 | Flunarizine orally disintegrating tablet and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586786A (en) * | 2014-12-25 | 2015-05-06 | 海南卫康制药(潜山)有限公司 | Cinnarizine composition freeze-dried tablet and preparation method thereof |
| CN104644577A (en) * | 2013-11-23 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Rivaroxaban orally-disintegrating tablet and preparation method thereof |
| CN112870337A (en) * | 2021-01-26 | 2021-06-01 | 浙江科瑞特生物科技有限公司 | Freeze-dried powder of composite hormone of somatotropin and chorionic gonadotropin and preparation method thereof |
| CN114246834A (en) * | 2021-12-30 | 2022-03-29 | 宣城柏维力生物工程有限公司 | Melatonin orally disintegrating preparation for improving sleep and production process thereof |
-
2009
- 2009-05-22 CN CN2009100518128A patent/CN101889986A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104644577A (en) * | 2013-11-23 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Rivaroxaban orally-disintegrating tablet and preparation method thereof |
| CN104586786A (en) * | 2014-12-25 | 2015-05-06 | 海南卫康制药(潜山)有限公司 | Cinnarizine composition freeze-dried tablet and preparation method thereof |
| CN112870337A (en) * | 2021-01-26 | 2021-06-01 | 浙江科瑞特生物科技有限公司 | Freeze-dried powder of composite hormone of somatotropin and chorionic gonadotropin and preparation method thereof |
| CN114246834A (en) * | 2021-12-30 | 2022-03-29 | 宣城柏维力生物工程有限公司 | Melatonin orally disintegrating preparation for improving sleep and production process thereof |
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Open date: 20101124 |