CN1853631A - Fast disintegrant containing paroxetine - Google Patents
Fast disintegrant containing paroxetine Download PDFInfo
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- CN1853631A CN1853631A CN 200510025445 CN200510025445A CN1853631A CN 1853631 A CN1853631 A CN 1853631A CN 200510025445 CN200510025445 CN 200510025445 CN 200510025445 A CN200510025445 A CN 200510025445A CN 1853631 A CN1853631 A CN 1853631A
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Abstract
A fast disintegrating tablet contains the paroxetine particles coated by acrylic resin, hydroxypropyl methylcellulose, or their mixture, excipient and disintegrant. Its disintegrating speed in saliva is shorter than 30 s.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition, be specifically related to a kind of quick oral cavity disintegration tablet that contains the active component paroxetine.
Background technology
Oral cavity rapid disintegration tablet (orally fast-disintegrating tablet, or orallyrapidly-disintegrating tablet) is a kind of new pharmaceutical preparation of rising both at home and abroad over past ten years, has taking convenience, disintegrate is rapid, rapid-action, bioavailability is high characteristics.The oral cavity rapid disintegration tablet can not need water, but only just administration under the effect of a small amount of saliva.In general, the oral cavity fast disintegrant contacts disintegrate in 1 minute after the saliva in the oral cavity.After the disintegrate, absorption has been accelerated in medicine stripping promptly or be dispersed into granule, makes onset rapid.This dosage form is applicable to: (1) has patient such as the child and the elderly patients of dysphagia; (2) digestive tract disease patient, they can't swallow or swallowing act causes serious vomiting reaction; (3) bed patient or work busy personage or traveller are especially when can't obtaining water; (4) in the time of need making the rapid onset of medicine, some disease such as cardiovascular disease, asthma, allergy, pain etc. all require quick administration.
The oral cavity rapid disintegration tablet is mainly by freeze-drying and pressing preparation.It is that active constituents of medicine and various adjuvant or additive are made solution or suspension that freeze-drying prepares oral rapidly disintegrating chip technology (Zydis), inject the mould of definite shape then, be frozen into solid rapidly, decompression makes water sublimed again, thereby forms the tablet with loose structure.This kind tablet configuration is loose, and small spaces is rich in inside, and the dissolving that can absorb water rapidly generally can be in 10 seconds in intraoral disintegration time.Adopt the drug main of the oral cavity rapid disintegration tablet that this technology makes to comprise: oxazepam, lorazepam, piroxicam, loperamide, famotidine, loratadine, enalapril, phenylpropanolamine/brompheniramine, ondansetron, Lizakuputan benzoate (Rizatriptan Benzoate), domperidone, nitroglycerin, isosorbidi dinitras, nifedipine, difenidol hydrochloride, meclozine hydrochloride etc. are (referring to J Pharm Pharmacol, 1998,50:375; PLA's Acta Pharmaceutica Sinica, 2000,16:206).But this method needs special freeze drying equipment, complex process, and the cost height, the tablet mechanical strength that makes is relatively poor.
The oral cavity rapid disintegration tablet porosity of pressing preparation is little, and disintegrate is slow slightly, but preparation technology is simple, and mechanical strength is better.The medicine that adopts pressing to make fast disintegrating oral tablet mainly contains Zolmitriptan (zomitriptan), that Puli of rice, baclofen, carbidopa/levodopa, carisoprodol (carisprodol) etc.
The disintegration time of the rapid disintegration tablet of pressing preparation depends mainly on selected disintegrating agent.Now normal adopt cross-linked carboxymethyl cellulose sodium with good disintegrating property, polyvinylpolypyrrolidone etc. (foreign medical science pharmacy fascicle, 1998,25:293).The consumption of filler and disintegrating agent has material impact to its disintegration time, and the consumption of disintegrating agent reaches as high as more than 15% of tablet weight.Filler is used lactose, mannitol, microcrystalline Cellulose etc. always.
Medicine with bitterness can adopt the powder coating method earlier medicine to be hidden flavor, and repress is made oral cavity quick disintegrating slice (specifically referring to the Chinese invention patent ublic specification of application, publication number CN1328446A, its full content is with reference to being incorporated into this).For the bad sense of taste being arranged, adopt powder coating technology can reach the purpose of taste masking as medicines such as numb, puckery, bitter, peppery, excitements.Powder coating technology commonly used has spray drying method and fluid bed boiling coating method etc., and wherein fluid bed boiling coating has coating efficient height, characteristics such as easy amplification.
Paroxetine (paroxetine, paxil, trade name seroxat Seroxat, the formal name used at school Paroxetine, be phenylpiperidine compound) have the height selectivity 5-hydroxy tryptamine (5-HT) reuptake retardation, its antidepressant effect intensity is similar to tricyclic antidepressant (TCA), and side effect then is evident as little than TCA, belongs to third generation antidepressant new drug.Paroxetine once carried out repeatedly having the clinical trial of contrast, proved the out-patient treatment that is applicable to slight or moderate depressive patients patient, and treatment effectiveness far wins placebo.Compare with tricyclic antidepressant, the curative effect in 6 weeks of administration is effective equally, and treatment effectiveness does not wane more than 1 year, and applicable to gerontal patient or patient that tricyclic antidepressant has been developed immunity to drugs.Quite a few is arranged in the patients with depression is the gerontal patient, and normal in addition spiritedness is depressed, and the performance of look asthenia is difficult for accepting to taking conventional tablet.In addition, paroxetine has intensive fiber crops, astringent taste feels, oral have a strong impulse sense.
Therefore, need a kind of new medicinal tablet of paroxetine as active component that comprise at present, it can improve the compliance of paroxetine for depressive patients, and it is more convenient that the patient is taken, and improves therapeutic quality.
Summary of the invention
The object of the present invention is to provide a kind of oral cavity rapid disintegration tablet that contains the active component paroxetine, to make things convenient for administration.Described paroxetine Orally-disintegrating tablet does not have bitterness basically, and disintegrate fast.
The invention provides a kind of oral cavity disintegration tablet, it comprises the paroxetine coated granule for the treatment of effective dose, and pharmaceutically acceptable excipient and disintegrating agent, the coating material of described paroxetine coated granule is selected from acrylic resin, hypromellose and composition thereof.
In a preferred embodiment of the present invention, described excipient is selected from filler, sweeting agent, binding agent, lubricant, coloring agent, aromatic or its mixture.
In another preferred embodiment of the present invention, described disintegrating agent is selected from polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch, low-substituted hydroxypropyl cellulose and composition thereof.
In another preferred embodiment of the present invention, the content of described paroxetine coated granule is 15%-65%, and preferred 20%-50% is in the gross weight of tablet.
In another preferred embodiment of the present invention, the content of described excipient is 30%-80%, and preferred 50%-75% is in the tablet total weight amount.
In another preferred embodiment of the present invention, the content of described disintegrating agent is 2%-25%, is preferably 5%-20%, in the gross weight of tablet.
In another preferred embodiment of the present invention, the coating material content in the described paroxetine coated granule is 2%～50%, is preferably 5%～25%, in the gross weight of tablet.
In another preferred embodiment of the present invention, the weight ratio of described excipient and paroxetine is 1-50, preferred 5-10.
In another preferred embodiment of the present invention, the mean diameter of described paroxetine coated granule is the 50-500 micron.
The present invention also provides a kind of method for preparing oral cavity disintegration tablet of the present invention, and it comprises:
A) active component paroxetine coated granule and various excipient and disintegrating agent were pulverized 80 eye mesh screens,
B) press recipe quantity precision weighing Paroxetine coated granule, disintegrating agent, various excipient after, with paroxetine coated granule and filler, disintegrating agent, solubilizing agent, sweeting agent, coloring agent mix homogeneously, add binding agent or wetting agent, make wet granular,
C) above-mentioned wet granular must be done granule after the uniform temperature drying, adds lubricant, and compacting obtains the described oral cavity disintegration tablet of claim 1.
The oral cavity rapid disintegration tablet of the paroxetine that the present invention relates to, the preparation of employing pressing, for reaching the effect that the effect that utilizes saliva in the oral cavity is a disintegratable, adopt the optimizing prescriptions in the pharmaceutics, make it can be in the oral cavity not reach disintegrate fast in time of 1 minute, be preferably less than 30 seconds with saliva.When the advantage of disintegrating tablet of the present invention is to take, need not drink water, only the effect by saliva just can make disintegration of tablet.Simultaneously, Paroxetine Orally-disintegrating tablet of the present invention does not have bitterness basically.
The specific embodiment
The invention provides to comprise the oral cavity rapid disintegration tablet of paroxetine a kind of, it comprises the paroxetine coated granule for the treatment of effective dose, pharmaceutically acceptable excipient and disintegrating agent, and the coating material of described paroxetine coated granule is selected from acrylic resin and hypromellose.
In tablet of the present invention, the paroxetine granule is the coated granule by the preparation of powder coating technology.Because the paroxetine bitter and puckery flavor, mouthfeel is bad, can cause not compliance of patient, but causes disintegrate slow behind the coating easily, the requirement that does not reach oral cavity disintegration tablet.So coating material of the present invention is selected from water solublity coating materials such as acrylic resin, hypromellose and composition thereof.The consumption of described coating material is the 2%-50% of tablet total amount, is preferably 5%-25%.
In tablet of the present invention, the paroxetine coated granule accounts for the 15%-65% of tablet weight, preferred 20%-50%.
Preferably, the mean diameter of described paroxetine coated granule is the 50-500 micron.
In tablet of the present invention, described disintegrating agent can be a disintegrating agent commonly used in the oral cavity disintegration tablet, is preferably selected from polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch, low-substituted hydroxypropyl cellulose and composition thereof.Described disintegrating agent is met the hundred times that can expand rapidly behind the water, reaches the effect that tablet is burst apart.The disintegration time of tablet shortens with the consumption increase of disintegrating agent.In the present invention, the consumption of described disintegrating agent is the 2%-25% of tablet total weight, is preferably 5%-20%.
Also comprise pharmaceutically acceptable excipient or its mixture in the tablet of the present invention, play respectively and hide flavor, keep the sheet weight, sheet shape, solubilising, bonding, painted, moistening, flavored action.The weight ratio of paroxetine coated granule and excipient is 1-50, is preferably 5-10.Usually, described excipient accounts for the 30%-80% of described tablet total weight amount, preferred 50%-75%.
Excipient in the tablet of the present invention can be a excipient that pharmaceutically can be thorny commonly used in the preparation oral cavity disintegration tablet, for example pharmaceutically acceptable filler, sweeting agent, binding agent, lubricant, coloring agent, aromatic or its mixture etc.
In tablet of the present invention, described pharmaceutically acceptable filler can be a filler commonly used in the oral cavity disintegration tablet.In a preferred embodiment of the present invention, described filler can be microcrystalline Cellulose, mannitol, lactose, xylitol, sucrose, glucose, starch, pregelatinized Starch, calcium sulfate, calcium carbonate, calcium phosphate, light magnesium oxide and composition thereof.In another preferred embodiment of the present invention, described filler is a microcrystalline Cellulose, because microcrystalline Cellulose has the effect of filler, disintegrating agent, binding agent, lubricant concurrently, adds the compressibility that proper proportion can improve the tablet powder body in the tablet.In another preferred embodiment of the present invention, described filler can also be a lactose, because bright and clean with the tablet appearance of lactose preparation, compressibility is good, and tablet can reach suitable hardness.Also have in the preferred embodiment of the present invention, described filler can be a mannitol, because can absorb heat during the mannitol dissolving, has sweet flavor, therefore has refrigerant tasty and refreshing sensation in the oral cavity.
Consumption for described filler does not have concrete restriction, but from the disintegrate of tablet, the stripping of active component paroxetine, the mouldability of tablet and the viewpoint of tablet appearance, filler preferably accounts for the 30%-75% of tablet total weight, is preferably 40-70%.
In tablet of the present invention, described pharmaceutically acceptable binding agent or wetting agent can be conventional binding agent or wetting agent in the preparation Orally-disintegrating tablet.Described binding agent can be the dry filler with adhesion characteristic, is suitable for becoming tablet with the direct compression prepared, and also can be aqueous rubber cement, solution, have bonding or wetting action.In a preferred embodiment of the present invention, described binding agent or wetting agent are selected from starch slurry, polyvidone rubber cement, hypromellose rubber cement, methylcellulose (sodium) rubber cement, carboxymethyl cellulose (sodium) rubber cement, water, ethanol and composition thereof.
Do not have concrete restriction for described adhesive consumption, but the 0.5%-5% of the common tablet total weight amount of described binding agent is preferably 1%-3%, in solid content.
Contain pharmaceutically acceptable sweeting agent and optional pharmaceutically acceptable coloring agent, aromatic, lubricant in the pharmaceutically acceptable excipient of tablet of the present invention.
In tablet of the present invention, described pharmaceutically acceptable sweeting agent can be a sweeting agent commonly used in the oral cavity disintegration tablet.In a preferred embodiment of the present invention, described sweeting agent is selected from aspartame, acesulfame potassium, saccharin sodium, Neohesperidin Dihydrochalcone and composition thereof.In the present invention, for the not concrete restriction of the consumption of sweeting agent.In a preferred embodiment of the present invention, the consumption of described sweeting agent is the 1%-10% of tablet total weight, is preferably 2%-5%.
In tablet of the present invention, also can choose the additive that is usually used in preparing tablet in the pharmaceuticals industries such as comprising pharmaceutically acceptable coloring agent, aromatic, lubricant wantonly.
In the present invention, for the not concrete restriction of the consumption of coloring agent, aromatic and lubricant, it can be the conventional amount used in this area, and for example coloring agent, aromatic and lubricant account for the 0.5-5% of tablet total weight respectively, preferred 1-3%.
Tablet of the present invention has suitable hardness, can tolerate the various processing under the routine operation condition and its character is not produced bigger influence.The hardness of common described tablet is between 20-70 newton.
Tablet of the present invention can this area routine the method preparation.The following method of a kind of preferable methods: earlier active component paroxetine coated granule and various excipient and disintegrating agent were pulverized 80 eye mesh screens, after pressing the recipe quantity precision weighing, with paroxetine coated granule and filler, disintegrating agent, solubilizing agent, sweeting agent, coloring agent mix homogeneously, add suitable amount of adhesive or wetting agent, make wet granular, must do granule after the uniform temperature drying, add lubricant, compacting forms.
Major advantage of the present invention is:
Oral cavity disintegration tablet of the present invention does not reach disintegrate fast in time of 1 minute with saliva in the oral cavity, be preferably less than 30 seconds.Being also advantageous in that when taking of disintegrating tablet of the present invention need do not drunk water, and only the effect by saliva just can make disintegration of tablet.Simultaneously, Paroxetine Orally-disintegrating tablet of the present invention does not have bitterness basically.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, or the condition of advising according to manufacturer.Unless otherwise indicated, otherwise % is weight percentage, and umber is parts by weight.
Embodiment
Universal method:
Slaking test:
The mensuration of disintegration time according to document (Powder Technology, 2002,122:188-198) report carry out.During mensuration, will be contained in the gram of 900 in flask water preheat to 37 ℃ of constant temperature, described flask is equipped with agitating device, and stirs water with certain speed.Oral cavity disintegration tablet is placed in the basket with netting on top that the aperture is No. 2 sieve apertures, and immerses together in the water, till granule behind the disintegration of tablet is all by the basket with netting on top eyelet.Granule is all counted disintegration time by the time of basket with netting on top eyelet behind the disintegration of tablet from immerse water.
Dissolution test
Carry out dissolution test according to two appendix XC of Pharmacopoeia of the People's Republic of China version in 2000 dissolution method.Oral cavity disintegration tablet is put under constant temperature and stable the stirring 900 milliliters, the dilute hydrochloric acid solution of 0.1 mol, in the time of the 3rd, 5,15,30,45 minute, get 5 milliliters of samples.With 0.45 micron filtering with microporous membrane sample, use ultraviolet spectrophotometer (293 nanometer) (Tianjin, island UV-2401 type) to measure absorbance then, calculate stripping medicament contg according to standard curve method, calculate stripping percent according to total dose again.Stir speed (S.S.) is 50 rev/mins, and thermostat temperature is 37 ± 0.5 ℃.
Preparation example 1 preparation paroxetine coated granule A1
Take by weighing 150 gram Eudragit Es 100 (German Rohm GmbH, Eudragit E100) and join in the 850 gram ethanol, stir up to forming homogeneous solution.With 500 gram paroxetine hydrochloride semihydrates (Zhejiang Prov JianFeng Pharmaceutical Co., Ltd), as 10% polyvidone of binding agent (the international special product of ISP company, PVP
K30) solution, as the micropowder silica gel (Ahua Pharmaceutical Co., Ltd., Liaocheng, Shandong) of fluidizer and above-mentioned homogeneous solution with GPCG1.1 boiling coating machine (Glatt company, GPCG1.1) disposable granulation.Carry out coating by top spray method, obtain paroxetine coated granule A1, coated granule weightening finish 180%.
Preparation example 2 preparation paroxetine coated granule A2
Take by weighing 50 gram hypromelloses (Shanghai Colorcon Coating Technology Co., Ltd, HPMC E50) and join in the 950 gram water, stir up to forming homogeneous solution.Carry out coating with the method identical, preparation paroxetine coated granule A2 with preparation example 1.
Preparation example 3 preparation paroxetine coated granule A3
Directly get commercially available Aquacoat (Shanghai Colorcon Coating Technology Co., Ltd, Surelease
).Carry out coating with the method identical, preparation paroxetine coated granule A3 with preparation example 1.
Embodiment 1
Take by weighing paroxetine hydrochloride coated granule, lactose (New Zealand lactose company), polyvinylpolypyrrolidone (the international special product of ISP company), A Siba sweet (The NutraSweet Company), the ferrum oxide (Shanghai Iron Oxide Pigment Factory) of quantity shown in the table 1, progressively increase method with paroxetine hydrochloride coated granule and various adjuvant mix homogeneously by equivalent.The mixture of gained is crossed 40 mesh sieves twice, and the gained material is placed appropriate containers.10% of adding 4.5 grams starch slurry (with pure amylometer) is made soft material in described container.Described soft material is crushed to wet granular by 20 mesh sieves.Described wet granular is placed in the dried enamel tray, and puts into the air blast thermostatic drying chamber together, 70 ℃ of dryings 2 hours.The weight of weighing dried particles, ratio (in dried particles weight) in 1 weight % adds magnesium stearate, be pressed into 1000 with ZDY-8 type single punch tablet machine (Far East, Shanghai pharmaceutical machine factory, ZDY-8 type) behind the mixing, obtain containing the oral cavity disintegration tablet of paroxetine.
Embodiment 2-3
Prepare oral cavity disintegration tablet with the method identical with embodiment 1, different is that its component that comprises and each components contents are as shown in table 1.
Table 1
| Embodiment 1 | Embodiment 2 | Embodiment 3 | |
| Paroxetine hydrochloride coated granule (hydrochloric paroxetine semihydrate), gram | A1，53.73 (22.76) | A2，51.86 (22.76) | A3，54.20 (22.76) |
| Lactose, gram | 158.6 | 158.6 | 158.6 |
| Polyvinylpolypyrrolidone, gram | 44.16 | 44.16 | 44.16 |
| A Siba is sweet, gram | 5 | 5 | 5 |
| Ferrum oxide, gram | 0.4 | 0.4 | 0.4 |
| 10% starch slurry, gram, | (4.5 with amylometer) | (4.5 with amylometer) | (4.5 with amylometer) |
| Magnesium stearate | 1 weight % | 1 weight % | 1 weight % |
Embodiment 4
Measure the disintegration time of 6 prepared disintegrating tablets of embodiment 1-3 respectively according to slaking test of the present invention, the results are shown in the following table 2.
Measure the stripping percent of 6 prepared disintegrating tablets of embodiment 1-3 respectively according to dissolution test of the present invention, the result is listed in respectively among the following table 3-5.
Table 2
| Numbering | Disintegration time, embodiment 1 (second) | Disintegration time, embodiment 2 (second) | Disintegration time, embodiment 3 (second) |
| 1 | 18 | 39 | 55 |
| 2 | 26 | 45 | 76 |
| 3 | 20 | 30 | 61 |
| 4 | 20 | 32 | 66 |
| 5 | 24 | 43 | 50 |
| 6 | 16 | 37 | 71 |
| Meansigma methods | 20.67±3.72 | 37.67±5.92 | 63.17±9.77 |
The stripping percent (%) of table 3 embodiment 1 gained disintegrating tablet
| Time (branch) | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| 3 | 82.51 | 81.34 | 86.03 | 83.51 | 76.27 | 81.34 | 81.84±3.23 |
| 5 | 94.24 | 95.52 | 97.69 | 98.19 | 96.10 | 94.24 | 96.00±1.68 |
| 15 | 97.84 | 97.92 | 100.9 | 97.22 | 100.0 | 97.69 | 98.60±1.5 |
| 30 | 99.04 | 100.2 | 101.0 | 100.6 | 99.58 | 101.1 | 100.2±0.81 |
| 45 | 101.0 | 99.97 | 100.5 | 102.4 | 98.11 | 101.7 | 100.6±1.5 |
The stripping percent (%) of table 4 embodiment 2 gained disintegrating tablets
| Time (branch) | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| 3 | 53.73 | 56.99 | 57.76 | 57.68 | 58.50 | 59.08 | 57.29±1.89 |
| 5 | 45.06 | 67.71 | 68.76 | 69.45 | 69.57 | 70.42 | 65.161±9.89 |
| 15 | 90.06 | 98.62 | 97.76 | 93.89 | 93.85 | 92.56 | 94.46±3.22 |
| 30 | 101.4 | 99.31 | 101.1 | 100.9 | 102.4 | 93.35 | 99.73±3.28 |
| 45 | 101.4 | 99.66 | 100.4 | 102.6 | 100.2 | 100.5 | 100.8±1.07 |
The stripping percent (%) of table 5 embodiment 2 gained disintegrating tablets
| Time (branch) | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 15 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 30 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 45 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
As show shown in the 2-5, coating material has bigger influence to the disintegrate and the stripping of paroxetine hydrochloride oral cavity disintegration tablet.By comparing disintegration time and stripping percent, preferably use acrylic resin and ethyl cellulose as coating material.
Embodiment 5-7
Prepare oral cavity disintegration tablet with the method identical with embodiment 1, each component that different is in the oral cavity disintegration tablet is as shown in table 6.Average every of the disintegrating tablet that obtains heavily is 250mg-275mg, and tensile strength is 20-50 newton.
Table 6
| Component | Embodiment 5 | Embodiment 6 | Embodiment 7 |
| Paroxetine coated granule A1, mg | 54.84 | 54.84 | 54.84 |
| Microcrystalline Cellulose, mg | 60 | 80 | 100 |
| Mannitol, mg | 100.00 | 100.00 | 100.00 |
| Polyvinylpolypyrrolidone, mg | 10 | 10 | 10 |
| Aspartame, mg | 5.00 | 5.00 | 5.00 |
| Ferrum oxide (red), mg | 0.4 | 0.4 | 0.4 |
| 5% starch slurry, mg | 8 (with amylometers) | 8 (with amylometers) | 8 (with amylometers) |
| Magnesium stearate, mg | 2.2 | 2.2 | 2.2 |
Stripping percent according to dissolution test measurement embodiment 5-7 gained oral cavity disintegration tablet of the present invention the results are shown in the following table 7.
The stripping percent (%) of table 7 embodiment 5-7 gained disintegrating tablet
| Time (minute) | Numbering | Meansigma methods | ||
| Embodiment 5 | Embodiment 6 | Embodiment 7 | ||
| 3 | 82.35 | 82.78 | 83.16 | 82.76±0.41 |
| 5 | 91.34 | 88.87 | 87.55 | 89.25±1.92 |
| 15 | 95.77 | 92.49 | 91.82 | 93.36±2.11 |
| 45 | 94.85 | 92.46 | 91.52 | 92.94±1.72 |
Embodiment 8-10
Make oral cavity disintegration tablet with the method identical with embodiment 1, the component of different is described oral cavity disintegration tablet is as shown in table 8 below.Average every of gained oral cavity disintegration tablet heavily is 190mg-370mg, and tensile strength is 20-50 newton.Because mannitol heat absorption when dissolving has the algefacient sensation when Orally disintegrating, help to improve the taste of tablet.
Table 8
| Component | Embodiment 8 | Embodiment 9 | Embodiment 10 |
| Paroxetine hydrochloride coated granule A1, mg | 25.00 | 50.00 | 75.00 |
| Mannitol, mg | 110.00 | 170.00 | 200.00 |
| Polyvinylpolypyrrolidone, mg | 25.00 | 40.00 | 60.00 |
| Aspartame, mg | 8.00 | 8.00 | 8.00 |
| Citric acid, mg | 5.00 | 5.00 | 5.00 |
| Sodium bicarbonate, mg | 6.00 | 6.00 | 6.00 |
| Poloxamer, mg | 2.00 | 2.00 | 2.00 |
| Ferrum oxide (red), mg | 0.3 | 0.4 | 0.4 |
| 5% starch slurry, mg | 6 (with amylometers) | 8 (with amylometers) | 8 (with amylometers) |
| Magnesium stearate, mg | 1.8 | 2.8 | 3.6 |
Disintegration time and stripping percent according to slaking test of the present invention and dissolution test measurement embodiment 8-10 gained oral cavity disintegration tablet the results are shown in the table 9.
The disintegration time and the stripping percent of table 9 embodiment 8-10 gained disintegrating tablet
| Embodiment 8 | Embodiment 9 | Embodiment 10 | |
| Disintegration time (second) | 18.48±3.37 | 26.89±2.66 | 30.12±4.62 |
| 3 minutes dissolutions | ＞80％ | ＞80％ | ＞80％ |
Embodiment 11-13
Make oral cavity disintegration tablet with the method identical with embodiment 1, the component of different is described oral cavity disintegration tablet is as shown in table 10 below.Average every of gained oral cavity disintegration tablet heavily is about 230mg, and tensile strength is 20-50 newton.
Table 10
| Component | Embodiment 11 | Embodiment 12 | Embodiment 13 |
| Paroxetine hydrochloride coated granule A2, mg | 50.00 | 50.00 | 50.00 |
| Glucose, mg | 50.00 | 25.00 | 75.00 |
| Pregelatinized Starch, mg | 50.00 | 75.00 | 25.00 |
| Carboxymethyl starch sodium, mg | 40.00 | 40 | 40 |
| Aspartame, mg | 8.00 | 8.00 | 8.00 |
| Citric acid, mg | 5.00 | 5.00 | 5.00 |
| Sodium bicarbonate, mg | 6.00 | 6.00 | 6.00 |
| Poloxamer, mg | 2.00 | 2.00 | 2.00 |
| Ferrum oxide (red), mg | 0.3 | 0.3 | 0.3 |
| 5% starch slurry, mg | 6 (with amylometers) | 6 (with amylometers) | 6 (with amylometers) |
| Magnesium stearate, mg | 2.3 | 2.3 | 2.3 |
Disintegration time and stripping percent according to slaking test of the present invention and dissolution test measurement embodiment 11-13 gained oral cavity disintegration tablet the results are shown in the table 11.
The disintegration time and the stripping percent of table 11 embodiment 11-13 gained oral cavity disintegration tablet
| Embodiment 11 | Embodiment 12 | Embodiment 13 | |
| Disintegration time (second) | 35.25±1.65 | 43.79±2.08 | 27.68±3.92 |
| 3 minutes dissolutions | ＞80％ | ＞80％ | ＞80％ |
Embodiment 14
Make oral cavity disintegration tablet with the method identical with embodiment 1, the component of different is described oral cavity disintegration tablet is as shown in table 12 below.Average every of gained oral cavity disintegration tablet heavily is about 300mg, and tensile strength is 20-50 newton.
Table 12
| Component | Embodiment 14 |
| Paroxetine hydrochloride coated granule A1 | 50.00mg |
| Microcrystalline Cellulose | 70.00mg |
| Low-substituted hydroxypropyl cellulose | 150.00mg |
| Saccharin sodium | 10.00mg |
| Tartaric acid | 5.00mg |
| Magnesium carbonate | 6.00mg |
| Poloxamer | 2.00mg |
| Ferrum oxide (red) | 4mg |
| 5% starch slurry | 8mg (with amylometer) |
| Magnesium stearate | 3mg |
Measure the disintegration time and the stripping percent of embodiment 14 gained disintegrating tablets according to slaking test of the present invention, the disintegration time that obtains is about 32.37 ± 3.35 seconds, and dissolution 3 minutes is greater than 80%.
Embodiment 15
Make oral cavity disintegration tablet with the method identical with embodiment 1, the component of different is described oral cavity disintegration tablet is as shown in table 13 below.Average every of gained oral cavity disintegration tablet heavily is about 300mg, and tensile strength is 20-50 newton.
Table 13
| Raw material and adjuvant | Embodiment 15 |
| Paroxetine hydrochloride coated granule A1 | 50.00mg |
| Microcrystalline Cellulose | 70.00mg |
| Low-substituted hydroxypropyl cellulose | 150.00mg |
| Saccharin sodium | 10.00mg |
| Tartaric acid | 5.00mg |
| Magnesium carbonate | 6.00mg |
| Sodium lauryl sulphate | 4.00mg |
| Ferrum oxide (red) | 4mg |
| 5% starch slurry | 8mg (with amylometer) |
| Magnesium stearate | 3mg |
Measure the disintegration time and the stripping percent of embodiment 15 gained disintegrating tablets according to slaking test of the present invention, the disintegration time that obtains is about 26.55 ± 3.40 seconds, and dissolution 3 minutes is greater than 80%.
Embodiment 16:
The bitterness of evaluation Paroxetine Orally-disintegrating tablet
Paroxetine Orally-disintegrating tablet to preparation among the embodiment 1 carries out subjective appreciation.Subjective appreciation personnel 20 age 18-40 by name year volunteer, the evaluation place is pharmaceutical college of a Fudan University pharmaceutics laboratory.Standards of grading are as follows:
| Scoring | Bitterness is described |
| 8～10 | There is not bitterness fully |
| 6～8 | Basically there is not bitterness |
| 4～6 | Little hardship |
| 2～4 | Very bitter, but can swallow |
| 0～2 | Very bitter, be difficult to swallow |
The paroxetine Orally-disintegrating tablet scoring statistical table that embodiment 1 makes
| Evaluation personnel number | 1# | 2# | 3# | 4# | 5# | 6# | 7# | 8# | 9# | 10# |
| Score | 8 | 10 | 9 | 8 | 10 | 7 | 8 | 9 | 9 | 8 |
| Evaluation personnel number | 11# | 12# | 13# | 14# | 15# | 16# | 17# | 18# | 19# | 20# |
| Score | 9 | 9 | 10 | 8 | 9 | 7 | 9 | 8 | 9 | 9 |
After analyzing by statistics, the bitterness score value that obtains Paroxetine Orally-disintegrating tablet of the present invention is 8.65 ± 0.86, generally believes that this compositions does not have bitterness basically.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (10)
1. oral cavity disintegration tablet, it comprises the paroxetine coated granule for the treatment of effective dose, and pharmaceutically acceptable excipient and disintegrating agent, and the coating material of described paroxetine coated granule is selected from acrylic resin, hypromellose and composition thereof.
2. disintegrating tablet as claimed in claim 1 is characterized in that described excipient is selected from filler, sweeting agent, binding agent, lubricant, coloring agent, aromatic or its mixture.
3. disintegrating tablet as claimed in claim 1 is characterized in that described disintegrating agent is selected from polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch, low-substituted hydroxypropyl cellulose and composition thereof.
4. disintegrating tablet as claimed in claim 1, the content that it is characterized in that described paroxetine coated granule is 15%-65%, preferred 20%-50% is in the gross weight of tablet.
5. disintegrating tablet as claimed in claim 1, the content that it is characterized in that described excipient is 30%-80%, preferred 50%-75% is in the tablet total weight amount.
6. disintegrating tablet as claimed in claim 1 is characterized in that the content of described disintegrating agent is 2%-25%, is preferably 5%-20%, in the gross weight of tablet.
7. disintegrating tablet as claimed in claim 1 is characterized in that the coating material content in the described paroxetine coated granule is 2%～50%, is preferably 5%～25%, in the gross weight of tablet.
8. disintegrating tablet as claimed in claim 1, the weight ratio that it is characterized in that described excipient and paroxetine is 1-50, preferred 5-10.
9. disintegrating tablet as claimed in claim 1, the mean diameter that it is characterized in that described paroxetine coated granule is the 50-500 micron.
10. method for preparing the described oral cavity disintegration tablet of claim 1, it comprises:
A) active component paroxetine coated granule and various excipient and disintegrating agent were pulverized 80 eye mesh screens,
B) press recipe quantity precision weighing Paroxetine coated granule, disintegrating agent, various excipient after, with paroxetine coated granule and filler, disintegrating agent, solubilizing agent, sweeting agent, coloring agent mix homogeneously, add binding agent or wetting agent, make wet granular,
C) above-mentioned wet granular must be done granule after the uniform temperature drying, adds lubricant, and compacting obtains the described oral cavity disintegration tablet of claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510025445A CN100588400C (en) | 2005-04-27 | 2005-04-27 | Fast disintegrant containing paroxetine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510025445A CN100588400C (en) | 2005-04-27 | 2005-04-27 | Fast disintegrant containing paroxetine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1853631A true CN1853631A (en) | 2006-11-01 |
| CN100588400C CN100588400C (en) | 2010-02-10 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200510025445A Expired - Fee Related CN100588400C (en) | 2005-04-27 | 2005-04-27 | Fast disintegrant containing paroxetine |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011012018A (en) * | 2009-07-02 | 2011-01-20 | Towa Yakuhin Kk | Pharmaceutical composition for oral administration of paroxetine hydrochloride hydrate, having inhibited retardation of disintegration |
| CN102302453A (en) * | 2011-09-14 | 2012-01-04 | 海南美大制药有限公司 | Paroxetine hydrochloride liposome solid preparation |
| CN102429883A (en) * | 2011-12-29 | 2012-05-02 | 天津市嵩锐医药科技有限公司 | Fluoxetine hydrochloride oral cavity disintegrating pharmaceutical composition |
| CN102525966A (en) * | 2010-12-13 | 2012-07-04 | 江苏万全特创医药生物技术有限公司 | Tablet containing paroxetine and preparation method thereof |
| CN102631329A (en) * | 2012-04-12 | 2012-08-15 | 无锡万全医药技术有限公司 | Oral paroxetine disintegrating tablet and preparation process thereof |
| CN108938580A (en) * | 2017-05-26 | 2018-12-07 | 万全万特制药江苏有限公司 | Paroxetine hydrochloride oral disintegrating tablet |
| CN111643474A (en) * | 2020-07-20 | 2020-09-11 | 华益药业科技(安徽)有限公司 | Preparation process of paroxetine film coated tablet |
| CN111803460A (en) * | 2020-07-20 | 2020-10-23 | 华益药业科技(安徽)有限公司 | Production process of paroxetine tablets |
| CN112137970A (en) * | 2019-06-28 | 2020-12-29 | 北京万全德众医药生物技术有限公司 | Paroxetine hydrochloride orally disintegrating tablet and preparation process thereof |
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- 2005-04-27 CN CN200510025445A patent/CN100588400C/en not_active Expired - Fee Related
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011012018A (en) * | 2009-07-02 | 2011-01-20 | Towa Yakuhin Kk | Pharmaceutical composition for oral administration of paroxetine hydrochloride hydrate, having inhibited retardation of disintegration |
| CN102525966A (en) * | 2010-12-13 | 2012-07-04 | 江苏万全特创医药生物技术有限公司 | Tablet containing paroxetine and preparation method thereof |
| CN102302453A (en) * | 2011-09-14 | 2012-01-04 | 海南美大制药有限公司 | Paroxetine hydrochloride liposome solid preparation |
| CN102302453B (en) * | 2011-09-14 | 2012-11-21 | 海南美大制药有限公司 | Paroxetine hydrochloride liposome solid preparation |
| CN102429883A (en) * | 2011-12-29 | 2012-05-02 | 天津市嵩锐医药科技有限公司 | Fluoxetine hydrochloride oral cavity disintegrating pharmaceutical composition |
| CN102631329A (en) * | 2012-04-12 | 2012-08-15 | 无锡万全医药技术有限公司 | Oral paroxetine disintegrating tablet and preparation process thereof |
| CN108938580A (en) * | 2017-05-26 | 2018-12-07 | 万全万特制药江苏有限公司 | Paroxetine hydrochloride oral disintegrating tablet |
| CN108938580B (en) * | 2017-05-26 | 2022-09-27 | 万全万特制药江苏有限公司 | Paroxetine hydrochloride oral disintegrating tablet |
| CN112137970A (en) * | 2019-06-28 | 2020-12-29 | 北京万全德众医药生物技术有限公司 | Paroxetine hydrochloride orally disintegrating tablet and preparation process thereof |
| CN111643474A (en) * | 2020-07-20 | 2020-09-11 | 华益药业科技(安徽)有限公司 | Preparation process of paroxetine film coated tablet |
| CN111803460A (en) * | 2020-07-20 | 2020-10-23 | 华益药业科技(安徽)有限公司 | Production process of paroxetine tablets |
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|---|---|
| CN100588400C (en) | 2010-02-10 |
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