A kind of oral cavity disintegration tablet that contains agomelatine
Technical field
The invention provides a kind of oral cavity disintegration tablet that contains agomelatine, agomelatine is carried out the enclose preparation, can solve the taste of principal agent effectively, and improve its dissolution.
Background technology
Agomelatine, N-[2-(7-methoxyl group-1-naphthyl) ethyl] acetamide is the selective agonist that a kind of melatonin can system's receptor.On the other hand, it is 5-HT
2cThe antagonist of receptor, this makes it have activity in the central nervous system.At major depression, seasonal constrain disorder, sleep disorder, cardiovascular disease, digestive system disease, insomnia and owing to the treatment of fatigue, appetite disorder and obesity that jet lag caused all has activity.
The advantage that oral cavity disintegration tablet has is to improve the blood drug level of medicine rapidly, can also avoid liver to be subjected to effect and to cause the medicine tachymetabolism simultaneously, has improved bioavailability.Mouthfeel is one of oral cavity disintegration tablet important parameters.Because agomelatine self has very strong tingling, can cause significant sensation at oral mucosa, the odor mask of normal conventional can't carry out taste masking to it.
Freeze Drying Technique is the routine techniques of preparation oral cavity disintegration tablet, is prepared into porous " oral lyophilization thing " by lyophilization, can disintegrate dispersion rapidly in mouth.This technology is carried out needs the complete and complicated commercial run of a cover, and equipment requirements is very high, causes the medicine cost of manufacturing to improve greatly.
Pharmacokinetic studies shows, for the parenteral approach, the bioavailability of agomelatine that by oral route is carried out administration is very low, and the difference in same individuality and between Different Individual is quite big.This is because the water solublity of agomelatine is very poor, has influenced the stripping of medicine, and its stripping is the speed limit process that absorbs, and usually is the main factor that influences bioavailability.
Based on above-mentioned reason,, reduce the industrialization cost in order to reduce the tingling of agomelatine, we adopt inclusion technique that agomelatine is carried out enclose, cover its disagreeable taste, and increase its dissolubility, mix wet granule compression tablet with pharmaceutically adjuvant again.The method can not only improve the dissolubility and the dissolution rate of agomelatine, has covered the tingling of agomelatine effectively, and promotes it to absorb in vivo, improves bioavailability, and simple to operate, has reduced cost, is very suitable for suitability for industrialized production.
Summary of the invention
The invention provides a kind of oral cavity disintegration tablet that contains agomelatine, is active component with the agomelatine behind the enclose, adds that adjuvant pharmaceutically is prepared into oral cavity disintegration tablet.
This oral cavity disintegration tablet, the mass ratio that it is characterized in that agomelatine and enclose material is 1: 4~1: 6, preferred 1: 4.Its inclusion method adopts fluid bed, spray drying, hypobaric drying method, and the enclose material is selected from cyclodextrin or polyacrylic resin, and polyacrylic resin is selected from EudragitE, EudragitL, the various models of EudragitS.
This oral cavity disintegration tablet, disintegration time are less than 3 minutes, preferably less than 1 minute.
The preparation technology of described oral cavity disintegration tablet is: take by weighing the clathrate of the agomelatine of recipe quantity, add the filler mix homogeneously.Binding agent is granulated, and adds disintegrating agent and lubricant outward, and tabletting promptly.
Comprise as the filler that is fit to oral cavity disintegration tablet of the present invention: dextrin, mannitol, sucrose, starch, ethyl cellulose, microcrystalline Cellulose.Preferred mannitol, starch, percentage by weight is 20%-50%.
Comprise as the disintegrating agent that is fit to oral cavity disintegration tablet of the present invention: carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone.Preferred carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, shared percentage by weight 5-20%.
The specific embodiment
Embodiment 1
The preparation prescription of oral cavity disintegration tablet:
Component |
Percentage ratio (%) |
Agomelatine |
??20 |
Mannitol |
??50 |
Starch |
??15 |
Low-substituted hydroxypropyl cellulose (outward) |
??10 |
Sucralose |
??2 |
Magnesium stearate |
??3 |
Preparation technology:
Take by weighing the agomelatine of recipe quantity, mannitol, starch mix homogeneously.As binding agent, make soft material with starch slurry, 16 orders are granulated.50 degree forced air dryings, 24 mesh sieve granulate.Add low-substituted hydroxypropyl cellulose, magnesium stearate and the sucralose of recipe quantity, mix homogeneously, the stamping of Φ 7mm scrobicula.
Embodiment 2:
Component |
Percentage ratio |
Agomelatine |
??8 |
??EudragitL100 |
??32 |
Mannitol |
??40 |
Starch |
??3 |
Carboxymethyl starch sodium |
??12 |
Component |
Percentage ratio |
Stevioside |
??2 |
Magnesium stearate |
??3 |
Preparation technology:
The EudragitL100 that takes by weighing recipe quantity is scattered in 95% the ethanol, after stirring, slowly adds the principal agent agomelatine, stirs enclose 15min.Drying under reduced pressure gets clathrate.Take by weighing agomelatine clathrate, the mannitol mix homogeneously of recipe quantity.As binding agent, make soft material with starch slurry, 16 orders are granulated.50 degree forced air dryings, 24 mesh sieve granulate.Add carboxymethyl starch sodium, magnesium stearate and the stevioside of recipe quantity, mix homogeneously.Φ 10mm tabletting.
Embodiment 3
The preparation prescription of oral cavity disintegration tablet:
Component |
Percentage ratio |
Agomelatine |
??6 |
??EudragitE100 |
??36 |
Mannitol |
??25 |
Starch |
??15 |
Low-substituted hydroxypropyl cellulose |
??13 |
Sucralose |
??2 |
Magnesium stearate |
??3 |
Preparation technology:
The EudragitE100 that takes by weighing recipe quantity is scattered in 95% the ethanol, after stirring, slowly adds the principal agent agomelatine, stirs enclose 15min.Drying under reduced pressure gets clathrate, takes by weighing agomelatine clathrate, mannitol, the starch of recipe quantity
Mix homogeneously.As binding agent, make soft material with starch slurry, 16 orders are granulated.50 degree forced air dryings, 24 mesh sieve granulate.Add low-substituted hydroxypropyl cellulose, magnesium stearate and the sucralose of recipe quantity, mix homogeneously.Φ 10mm tabletting.
Embodiment 4
The sample of the foregoing description is carried out the detection of bitterness, dissolution (2005 editions pharmacopeia appendix X A inspection techniques disintegration) and dissolution (2005 editions pharmacopeia appendix X C dissolution method first methods), and the result is as follows:
|
Embodiment 1 |
Embodiment 2 |
Embodiment 3 |
Bitterness |
Obvious tingling is arranged |
Do not have |
Do not have |
Disintegration |
??30s |
??30s |
??60s |
The 30min stripping |
??95.06% |
??98.98% |
??90.03% |
Can prove by above embodiment, adopt inclusion method to prepare the agomelatine oral cavity disintegration tablet, can not only cover bitterness, and can improve the dissolution of agomelatine, the method simple possible helps suitability for industrialized production.