CN102106836A - Almotriptan-containing buccal adhesive tablet as well as preparation method and application thereof - Google Patents
Almotriptan-containing buccal adhesive tablet as well as preparation method and application thereof Download PDFInfo
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- CN102106836A CN102106836A CN 201010617084 CN201010617084A CN102106836A CN 102106836 A CN102106836 A CN 102106836A CN 201010617084 CN201010617084 CN 201010617084 CN 201010617084 A CN201010617084 A CN 201010617084A CN 102106836 A CN102106836 A CN 102106836A
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- almotriptan
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- oral cavity
- adhesion
- pastille
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Abstract
The invention provides an almotriptan-containing buccal adhesive tablet. The tablet consists of a medicine-containing adhesive part and a waterproof protection part, wherein the medicine-containing adhesive part comprises the following components in percentage by weight: 1 to 30 percent of almotriptan, 12 to 85 percent of adhesive agent, and 5 to 30 percent of excipient; and the waterproof protection part comprises the following components in percentage by weight: 1 to 15 percent of film-forming agent, 0.1 to 10 percent of plasticizer, and 0.001 to 3 percent of pigment. The invention also provides a method for preparing the almotriptan-containing buccal adhesive tablet. The medicine-containing adhesive part of the buccal adhesive tablet is in directly contact with an oral mucosa, and the medicament is directly absorbed to enter systemic circulation through the oral mucosa, thus the influence on gastrointestinal tract and pass effect of liver are avoided, and the occurrence of adverse reaction is reduced. Furthermore, the buccal adhesive tablet provided by the invention can be adhered to the oral mucosa for a long time, so that stable blood concentration is maintained, and the bioavailability is improved.
Description
Technical field
The present invention relates to the migrainous medicine of a kind of treatment, relate in particular to a kind of oral cavity adhesion tablet that contains almotriptan and preparation method thereof.
Background technology
Migraine is one of commonly encountered diseases of Neurology Department, and sickness rate accounts for population more than 10%.International headache association is defined as intermittent headache outbreak with migraine and with autonomic imbalance.Clinical manifestation is paroxysmal headache, often with dizzy, hearing disability etc.The M-F of migraine sickness rate is 1: 4, the young and middle-aged people at 25～55 years old of mostly occurring.With the increase of operating pressure, migrainous sickness rate presents the situation of continuous rising with the quickening pace of modern life, no matter in developed country or developing country, has become puzzlement people's a kind of commonly encountered diseases, frequently-occurring disease.Migraine has had a strong impact on patient's quality of life and work efficiency, causes huge burden for family and society.The shortage of migrainous high incidence and efficient medicine makes that the market of migraine remedy is huge, has a extensive future.This shows, develop effective migraine treatment medicine and dosage form, be significant, also is very urgent and necessary.
Migraine is relevant with the brain superexcitation, 5-hydroxy tryptamine (5-HT) systolic and diastolic function to blood vessel in migrainous episode process plays crucial effect, outbreak is initial because psychentonia, hunger or the high tyramine food of ingesting, 5-HT too much can cause vasoconstriction and tendencys such as vision, paraesthesia occur in the blood plasma, then 5-HT content descends, and distends the blood vessels and headache occurs.The chemical name of almotriptan is 3-(2-decil)-5-(1-pyrrolidinyl sulfonymethyl)-1H-indole, and molecular formula is C
17H
19D
6N
3O
2S, relative molecular weight are 341.5, and the CAS registration number is 154323-57-6.Structural formula is as follows:
Almotriptan is migrainous specificity cushion, and its tablet went on the market in U.S.'s approval May calendar year 2001, and this medicine is 5-HT
1B/1DReceptor selective agonists is to the 5-HT of intracranial vessel
1B/1DReceptor has the high degree of specificity affinity, to 5-HT
1FReceptor also has higher affinity, but to 5-HT
1AReceptor and 5-HT
7Receptor affinity a little less than, other receptor is not had affinity or very weak affinity is only arranged, can make majority have 5-HT
1B/1DThe vasoconstriction of receptor, especially strong to the contraction of people's meninges tremulous pulse and temporo tremulous pulse, bring into play therapeutical effect by making cerebrovascular contraction and cerebral blood flow reallocation.
Almotriptan oral absorption speed is medium, single oral 5～200mg, T
MaxIt is 1.4～3.8 hours.Behind the single oral 12.5mg, t
1/2Be 3.1～4 hours, C
MaxBe 29～50 μ g/L, AUC is 0.229～0.266mgh/L, and in 5～200mg dosage range, AUC and C
MaxAll be directly proportional with dosage.This product distributes wide, and its apparent volume of distribution is 180～200L, and plasma protein binding rate is about 35%, the oral 25mg of healthy volunteer, and the average absolute bioavailability is about 70%; Oral 5～200mg, relative bioavailability about 80%.This product 45% is discharged through kidney with the prototype medicine, and 45% through liver metabolism.In vitro tests shows that mainly through monoamine oxidase, MAO (MAO)-A and Cytochrome P450 (CYP) isozyme 3A metabolism, other has part through the CYP2D6 metabolism to this product, and metabolite is mainly the γ-An Jidingsuan and the ethychlozate derivative of non-activity.
Though the oral drugs of almotriptan are easy to use, patient's compliance and toleration are better, but the common symptom of migraine mainly shows as nauseating, vomiting during gastrointestinal dysfunction, even there is not the symptom of feeling sick, also may cause delayed gastric emptying and oral drugs to absorb reduces, bioavailability is not high, visible oral administration route poor effect; Moreover, because the outbreak of this disease varies with each individual, because of the time different, needs of patients has more therapeutic scheme that selection is provided.
Summary of the invention
The object of the present invention is to provide a kind of oral cavity adhesion tablet that contains almotriptan, it treats migraine with almotriptan as active component, and the present invention also provides the preparation method and the application thereof of this preparation.The oral cavity adhesion tablet messenger drug thing oral transmucosal that the present invention makes as active component with almotriptan directly absorbs and enters the body circulation, avoids gastrointestinal effects and liver first-pass effect, has reduced incidence rate of adverse reaction, has improved bioavailability.
For solving the problems of the technologies described above, the present invention by the following technical solutions:
A kind of oral cavity adhesion tablet that contains almotriptan; it is made up of pastille adhesion section, waterproofing protection part two parts; described pastille adhesion section contains 1%～30% almotriptan, 12%～85% adhesive agent and 5%～30% excipient by weight percentage, and described waterproofing protection partly contains 1%～15% film former, 0.1%～10% plasticizer and 0.001%～3% pigment by weight percentage.
Further, described pastille adhesion section contains 5%～18% almotriptan.
Further again, described pastille adhesion section contains 50%～80% adhesive agent.
Wherein, described adhesive agent is one or more in carbomer 934, carbomer 934 P, hypromellose, hydroxypropyl cellulose or the sodium carboxymethyl cellulose.
Described excipient is one or more in lactose, mannitol, magnesium stearate, micropowder silica gel or the microcrystalline Cellulose.
Described film former is one or more in ethyl cellulose, cellulose acetate or the copolyvidone.
Described plasticizer is one or more in diethyl phthalate, Oleum Ricini, Macrogol 4000 or the polyethylene glycol 6000.
Further, a kind of preparation method that contains the oral cavity adhesion tablet of almotriptan, it may further comprise the steps:
Step a, making pastille adhesion section: after the almotriptan pulverizing, weigh according to the ratio of percentage by weight, behind the mix homogeneously, cross the 80-90 mesh sieve, with putting down of tablet machine towards direct compression with adhesive agent, excipient.
Step b, spraying waterproofing protection part: film former, plasticizer and pigment are dissolved in the solvent, make homogeneous solution, evenly be sprayed at pastille adhesion section one side surface, after 20～40 ℃ of dryings, form the waterproofing protection part with Membrane jetter.
Further, described tablet machine is flat is 5.5-7mm towards diameter.
During a kind of purposes that contains the oral cavity adhesion tablet of almotriptan is to treat, the application in the severe migraine remedy.
Owing to adopt technical scheme of the present invention, the present invention has following beneficial effect: the pastille adhesion section of oral cavity adhesion tablet directly contacts with oral mucosa, medicine can directly absorb through oral mucosa and enter the body circulation, gastrointestinal effects and the liver first-pass effect of avoiding oral drugs to cause, thereby reduced incidence rate of adverse reaction, and oral cavity adhesion tablet of the present invention can stick to the oral mucosa place for a long time, kept stable blood concentration, improves bioavailability.
The specific embodiment
Embodiment 1
The oral cavity adhesion tablet of almotriptan (1000)
Almotriptan 6.25g
Carbomer 934 15g
Hydroxypropyl cellulose 47g
Lactose 11g
Magnesium stearate 0.8g
Ethyl cellulose 5g
Polyethylene glycol 6000 0.5g
Copolyvidone 0.4g
Lemon yellow 2mg
Preparation method is as follows:
Behind almotriptan, carbomer 934, hydroxypropyl cellulose, lactose, magnesium stearate mix homogeneously; cross 80 mesh sieves; diameter 6mm with tablet machine is flat towards direct compression; ethyl cellulose, polyethylene glycol 6000, copolyvidone, lemon yellow are dissolved with 95% alcoholic solution 100ml; evenly be sprayed at a side surface of pastille adhesion section with Membrane jetter; after 35～40 ℃ of dryings, form the waterproofing protection part.
Embodiment 2
The oral cavity adhesion tablet of almotriptan (1000)
Almotriptan 6.25g
Carbomer 934 P 10g
Hypromellose 43g
Mannitol 20g
Magnesium stearate 0.5g
Cellulose acetate 8g
Macrogol 4000 1g
Copolyvidone 0.8g
Lemon yellow 2mg
Preparation method is as follows:
Behind almotriptan, carbomer 934 P, hypromellose, mannitol, magnesium stearate mix homogeneously; cross 90 mesh sieves; diameter 7mm with tablet machine is flat towards direct compression; with cellulose acetate, Macrogol 4000, copolyvidone, lemon yellow acetone: water (95%: 5%) solution 100ml dissolving; evenly be sprayed at pastille adhesion section one side surface with Membrane jetter; after 20～25 ℃ of dryings, form the waterproofing protection part.
Embodiment 3
The oral cavity adhesion tablet of almotriptan (1000)
Almotriptan 6.25g
Carbomer 934 14g
Sodium carboxymethyl cellulose 45g
Mannitol 14g
Micropowder silica gel 0.5g
Ethyl cellulose 5g
Diethyl phthalate 1g
Copolyvidone 0.8g
Erythrosine 2mg
Preparation method is as follows:
Behind almotriptan, carbomer 934, sodium carboxymethyl cellulose, mannitol, micropowder silica gel mix homogeneously; cross 80 mesh sieves; diameter 6mm with tablet machine is flat towards direct compression; ethyl cellulose, diethyl phthalate, copolyvidone, erythrosine are dissolved with 95% alcoholic solution 100ml; evenly be sprayed at pastille adhesion section one side surface with Membrane jetter; after 35～40 ℃ of dryings, form the waterproofing protection part.
With the sample that above embodiment makes, according to dissolution test method (two appendix XD of Chinese Pharmacopoeia version in 2010 three therapeutic methods of traditional Chinese medicine), be solvent with the hydrochloric acid 900ml of 0.1mol/L, rotating speed is that per minute 50 changes, 32 ± 0.5 ℃ of operations in accordance with the law of water temperature.At 2,4,8,10 hours, sampling utilized the determined by ultraviolet spectrophotometry release, and release the results are shown in following table.
The result shows that the time of the sustainable slow release medicine of this product is about 8 hours.This tablet adhesion time in the healthy volunteer oral cavity on average reaches 7.9 hours.
Embodiment 4
The oral cavity adhesion tablet of almotriptan (1000)
Almotriptan 12.5g
Carbomer 934 13g
Hydroxypropyl cellulose 40g
Mannitol 14g
Magnesium stearate 1g
Cellulose acetate 7g
Macrogol 4000 1g
Copolyvidone 0.8g
Erythrosine 2mg
Preparation method is as follows:
Behind almotriptan, carbomer 934, hydroxypropyl cellulose, mannitol, magnesium stearate mix homogeneously; cross 80 mesh sieves; diameter 6mm with tablet machine is flat towards direct compression; with cellulose acetate, Macrogol 4000, copolyvidone, erythrosine acetone: water (95%: 5%) solution 100ml dissolving; evenly be sprayed at a side surface of pastille adhesion section with Membrane jetter; after 20～25 ℃ of dryings, form the waterproofing protection part.
Embodiment 5
The oral cavity adhesion tablet of almotriptan (1000)
Almotriptan 12.5g
Carbomer 934 P 15g
Hypromellose 48g
Lactose 7g
Magnesium stearate 1g
Cellulose acetate 9g
Polyethylene glycol 6000 0.6g
Copolyvidone 0.8g
Erythrosine 1mg
Preparation method is as follows:
Behind almotriptan, carbomer 934 P, hypromellose, lactose, magnesium stearate mix homogeneously; cross 90 mesh sieves; diameter 6mm with tablet machine is flat towards direct compression; with cellulose acetate, polyethylene glycol 6000, copolyvidone, erythrosine acetone: water (95%: 5%) solution 100ml dissolving; evenly be sprayed at a side surface of pastille adhesion section with Membrane jetter; after 20～25 ℃ of dryings, form the waterproofing protection part.
The oral cavity adhesion tablet of embodiment 6 almotriptans (1000)
Almotriptan 12.5g
Carbomer 934 14g
Sodium carboxymethyl cellulose 43g
Lactose 10g
Micropowder silica gel 1g
Ethyl cellulose 6g
Oleum Ricini 0.8g
Copolyvidone 1g
Erythrosine 1mg
Preparation method is as follows:
Behind almotriptan, carbomer 934, sodium carboxymethyl cellulose, lactose, micropowder silica gel mix homogeneously; cross 80 mesh sieves; diameter 5.5mm with tablet machine is flat towards direct compression; ethyl cellulose, Oleum Ricini, copolyvidone, erythrosine are dissolved with 95% alcoholic solution 100ml; evenly be sprayed at a side surface of pastille adhesion section with Membrane jetter; after 20～25 ℃ of dryings, form the waterproofing protection part.
With the sample that above embodiment 3-6 makes, according to dissolution test method (two appendix XD of Chinese Pharmacopoeia version in 2010 three therapeutic methods of traditional Chinese medicine), be solvent with the hydrochloric acid 900ml of 0.1mol/L, rotating speed is that per minute 50 changes, 32 ± 0.5 ℃ of operations in accordance with the law of water temperature.At 2,4,8,10 hours, sampling utilized the determined by ultraviolet spectrophotometry release, and release the results are shown in following table
The result shows that the time of the sustainable slow release medicine of this product is about 8 hours.This tablet adhesion time in the healthy volunteer oral cavity on average reaches 7.9 hours.
The above only is preferred embodiment of the present invention, is not to be the restriction of the present invention being made other form, and any those skilled in the art may utilize the technology contents of above-mentioned announcement to be changed or be modified as the equivalent embodiment of equivalent variations.But every technical solution of the present invention content that do not break away to any simple modification, equivalent variations and remodeling that above embodiment did, still belongs to the protection domain of technical solution of the present invention according to technical spirit of the present invention.
Claims (10)
1. oral cavity adhesion tablet that contains almotriptan; it is made up of pastille adhesion section, waterproofing protection part two parts; it is characterized in that: described pastille adhesion section contains 1%～30% almotriptan, 12%～85% adhesive agent and 5%～30% excipient by weight percentage, and described waterproofing protection partly contains 1%～15% film former, 0.1%～10% plasticizer and 0.001%～3% pigment by weight percentage.
2. a kind of according to claim 1 oral cavity adhesion tablet that contains almotriptan is characterized in that described pastille adhesion section contains 5%～18% almotriptan.
3. a kind of according to claim 1 oral cavity adhesion tablet that contains almotriptan is characterized in that described pastille adhesion section contains 50%～80% adhesive agent.
4. as a kind of oral cavity adhesion tablet that contains almotriptan as described in the claim 1,2 or 3, it is characterized in that described adhesive agent is one or more in carbomer 934, carbomer 934 P, hypromellose, hydroxypropyl cellulose or the sodium carboxymethyl cellulose.
5. as a kind of oral cavity adhesion tablet that contains almotriptan as described in the claim 1,2 or 3, it is characterized in that described excipient is one or more in lactose, mannitol, magnesium stearate, micropowder silica gel or the microcrystalline Cellulose.
6. as a kind of oral cavity adhesion tablet that contains almotriptan as described in the claim 1,2 or 3, it is characterized in that described film former is one or more in ethyl cellulose, cellulose acetate or the copolyvidone.
7. as a kind of oral cavity adhesion tablet that contains almotriptan as described in the claim 1,2 or 3, it is characterized in that described plasticizer is one or more in diethyl phthalate, Oleum Ricini, Macrogol 4000 or the polyethylene glycol 6000.
8. a kind of according to claim 1 preparation method that contains the oral cavity adhesion tablet of almotriptan is characterized in that it may further comprise the steps:
Step a, making pastille adhesion section: after the almotriptan pulverizing, weigh according to the ratio of percentage by weight, behind the mix homogeneously, cross the 80-90 mesh sieve, with putting down of tablet machine towards direct compression with adhesive agent, excipient.
Step b, spraying waterproofing protection part: film former, plasticizer and pigment are dissolved in the solvent, make homogeneous solution, evenly be sprayed at pastille adhesion section one side surface, after 20～40 ℃ of dryings, form the waterproofing protection part with Membrane jetter.
9. as a kind of preparation method that contains the oral cavity adhesion tablet of almotriptan as described in the claim 8, it is characterized in that described tablet machine flat be 5.5-7mm towards diameter.
10. as a kind of oral cavity adhesion tablet that contains almotriptan as described in claim 1 or 2 or 3 or 8, the application during its purposes is to treat, in the severe migraine remedy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010617084 CN102106836A (en) | 2010-12-21 | 2010-12-21 | Almotriptan-containing buccal adhesive tablet as well as preparation method and application thereof |
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| CN 201010617084 CN102106836A (en) | 2010-12-21 | 2010-12-21 | Almotriptan-containing buccal adhesive tablet as well as preparation method and application thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105078919A (en) * | 2015-08-27 | 2015-11-25 | 青岛海之源智能技术有限公司 | Clopidogrel hydrogen sulfate oral patch and method for manufacturing same |
| CN110403935A (en) * | 2019-08-15 | 2019-11-05 | 兆科药业（广州）有限公司 | A kind of inhibitors of phosphodiesterase-4 pharmaceutical composition and preparation method thereof for treating canker sore |
| CN115006356A (en) * | 2022-05-09 | 2022-09-06 | 广西纯正堂制药有限公司 | Lumbrukinase oral adhesive tablet and preparation method and application thereof |
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| CN1615857A (en) * | 2004-09-28 | 2005-05-18 | 天津药物研究院 | Amlexanox double layer oral patches and its preparing method |
| CN101450087A (en) * | 2007-11-30 | 2009-06-10 | 凌沛学 | Adonis amurensis total-flavone mouth paster and preparation method thereof |
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2010
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Patent Citations (2)
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| CN1615857A (en) * | 2004-09-28 | 2005-05-18 | 天津药物研究院 | Amlexanox double layer oral patches and its preparing method |
| CN101450087A (en) * | 2007-11-30 | 2009-06-10 | 凌沛学 | Adonis amurensis total-flavone mouth paster and preparation method thereof |
Non-Patent Citations (2)
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105078919A (en) * | 2015-08-27 | 2015-11-25 | 青岛海之源智能技术有限公司 | Clopidogrel hydrogen sulfate oral patch and method for manufacturing same |
| CN110403935A (en) * | 2019-08-15 | 2019-11-05 | 兆科药业（广州）有限公司 | A kind of inhibitors of phosphodiesterase-4 pharmaceutical composition and preparation method thereof for treating canker sore |
| CN110403935B (en) * | 2019-08-15 | 2022-08-09 | 兆科药业（广州）有限公司 | Phosphodiesterase-4 inhibitor pharmaceutical composition for treating oral ulcer and preparation method thereof |
| CN115006356A (en) * | 2022-05-09 | 2022-09-06 | 广西纯正堂制药有限公司 | Lumbrukinase oral adhesive tablet and preparation method and application thereof |
| CN115006356B (en) * | 2022-05-09 | 2024-02-20 | 九华华源药业(桂林)有限公司 | Lumbrukinase oral cavity adhesive tablet, and preparation method and application thereof |
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Application publication date: 20110629 |