CN100358517C - Tamoxifen citrate oral disintegrating tablet and its preparation method - Google Patents
Tamoxifen citrate oral disintegrating tablet and its preparation method Download PDFInfo
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- CN100358517C CN100358517C CNB2004100357782A CN200410035778A CN100358517C CN 100358517 C CN100358517 C CN 100358517C CN B2004100357782 A CNB2004100357782 A CN B2004100357782A CN 200410035778 A CN200410035778 A CN 200410035778A CN 100358517 C CN100358517 C CN 100358517C
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Abstract
The present invention relates to a tamoxifen citrate oral disintegrating tablet which is composed of tamoxifen citrate, disintegrating agents, drying adhesives, fillers, glidants, lubricants, corrigents, etc. The tamoxifen citrate, sodium carboxymethyl starch, cellulose microcrystalline, lactose, micro-powdery silica gel, magnesium stearate and the corrigents are respectively crushed and sieved with a 100-mesh sieve and then uniformly blended; the oral disintegrating tablet can be finally obtained through a direct powder tablet compressing method. The oral disintegrating tablet can be disintegrated rapidly in oral cavities without water, and the disintegrating time in oral cavities is within 20 seconds; the disintegrating time outside human bodies is less than one minute; the present invention has the advantages of high dissolution speed and high bioavailability; the dissolution in 15 minutes reaches over 89.4% and is equivalent to the dissolution of a common tablet in 30 minutes.
Description
Affiliated technical field:
The present invention relates to contain the pharmaceutical composition of Tamoxifen Citrate, is the improvement technology about a kind of Tamoxifen Citrate oral formulations.
Technical background:
Tamoxifen Citrate is a kind of nonsteroidal anti-estrogens medicine, since coming out the seventies, always as the standard care medicine of breast carcinoma hormonotherapy, in clinical, be used for various and treatment each primary breast cancer patient, in recent years, Tamoxifen Citrate is a still line medication of endocrinotherapy for breast cancer not, also is used for the breast carcinoma prophylactic treatment, and the whole world has 4,500,000 patients to use tamoxifen treatment breast carcinoma every year approximately.
Tamoxifen Citrate is insoluble in water, and bioavailability and dissolution in vitro characteristic have certain dependency in its body.The Tamoxifen Citrate preparation that uses clinically at present is the Tamoxifen Citrate ordinary tablet.Wang Ruiqin etc. had once investigated the disintegration of Tamoxifen Citrate sheet of domestic 4 manufacturer production and dissolution (referring to " China Dispensary ", 2002,13 (7): 431-432), though 4 kinds of products all meet " the regulation of Chinese pharmacopoeia, but because it is different with technology to produce prescription, its disintegration time does not wait from 1.87 ± 0.18min to 9.07 ± 2.10min, causes the Tamoxifen Citrate dissolution to have significant difference.Existing preparation has influenced this drug absorption and bioavailability because dissolution rate is slow.
Summary of the invention:
The object of the present invention is to provide a kind of taking convenience, absorb the Tamoxifen Citrate orally disintegrating tablet preparation fast, that bioavailability is high.
For the medicine that is insoluble in water, bioavailability and external dissolution characteristic have certain dependency in its body.Because Tamoxifen Citrate is insoluble in water, therefore, the present invention promotes the absorption of human body to Tamoxifen Citrate to shorten the disintegration of tablet time, to improve its dissolution speed and start with, make Tamoxifen Citrate can reach effective blood drug concentration fast, onset rapidly.In addition, Tamoxifen Citrate also is used for the putting of tumor, chemotherapy process, the common untoward reaction of patient is vomiting, solution of the present invention is that Tamoxifen Citrate is mixed with a kind of Tamoxifen Citrate oral cavity disintegration tablet that does not need water to get final product rapid disintegrate in the oral cavity, both can accelerate dissolution rate, be applicable to the chemotherapy of tumors patient that water breakthrough is promptly vomitted again, and the patient under old people and the special environment that can not obtain water.
Oral cavity disintegration tablet is that a kind of water that do not need in the oral cavity can disintegrate or dissolved tablet.Do not need water when taking such preparation or only need use low amounts of water, also need not to chew, tablet places lingual surface to meet the rapid disintegrate of saliva, borrows swallowing act to go into the stomach onset.Tamoxifen Citrate is made oral cavity disintegration tablet, disintegration time is obviously shortened, dissolution rate improves, and absorbs soon, and the bioavailability height improves the compliance of clinical application.
The technical essential of preparation oral cavity disintegration tablet is to make the quick disintegrate of tablet, has good mouthfeel again, does not have grittiness in the oral cavity, so the nature difference of principal agent is for mouthfeel with have largely influence disintegration.Tamoxifen Citrate is white or off-white color crystalline powder, odorless.Behind its micronization, in the oral cavity, there is no grittiness, no special odor, but have bitterness.According to these characteristics, adopted correctives that its mouthfeel is adjusted.
The content of Tamoxifen Citrate in every is 15.2mg, and is little in the ratio that whole tablet Chinese traditional medicine accounts for, and the flowability of raw material itself and compressibility are less to the influence of direct compression, and the flowability of mixed-powder and compressibility depend mainly on the performance of filler.Therefore, select proper supplementary material kind and ratio for use, make the disintegration rate of oral cavity disintegration tablet fast, suitable hardness is arranged, preparation process is easy to large-scale production.
Oral cavity disintegration tablet of the present invention is made up of components such as Tamoxifen Citrate, disintegrating agent carboxymethyl base Starch Sodium, dry adhesive microcrystalline Cellulose, magnesium stearate lubricant and correctives mannitol.Its constituent content, be by weight percentage: the Tamoxifen Citrate of 20.0-40.0wt%, the carboxymethyl starch sodium of 5.0-10.0wt%, the microcrystalline Cellulose of 45.0-55.0wt%, the micropowder silica gel of 5.0-10.0wt%, the magnesium stearate of 1.0-2.0wt%, the lactose of 1.0-3.0wt%, the aspartame of 0.1-0.5wt%.
The disintegration of oral cavity disintegration tablet and disintegrating agent performance are closely related.The mechanism of action of disintegrating agent is still not exclusively clear and definite, and it is generally acknowledged to be subjected to the effect of following two aspects to make disintegration of tablet: (1) expansion: disintegrating agent mostly is the high molecular weight hydrophilic material, after the compacting in flakes, meets water and is easy to wetted and expands by self make disintegration of tablet; (2) capillarity: the adjuvant of some disintegrating agents and filler, particularly direct compression mostly is spheroidal hydrophilic aggregation body, form countless holes and capillary tube adding to depress, have intensive water absorption, hydrone is entered rapidly among the tablet, make whole tablet moistening and disintegrate.Suction back powder expands and does not dissolve, and does not form colloid solution, is unlikely to hinder the continuation infiltration of hydrone, makes the further disintegrate of tablet.The present invention is a disintegrating agent with the carboxymethyl starch sodium, and carboxymethyl starch sodium is formed by glucose polymerisation, and the introducing of carboxymethyl has starch relatively poor to draw moist and imbibition.Its degree of exchange of the carboxymethyl starch sodium of selecting for use among the present invention is generally about 0.3-0.5, and swellbility is 5ml/g, all can use as commercial goods Primojel, Explotab or DST etc.
Microcrystalline Cellulose is mobile and compressibility is good, is suitable for direct compression, plays a part dry adhesive in direct compression technology.Secondly, microcrystalline Cellulose also has good disintegration, also helps disintegrate in this product, but its swellbility lower (3.4ml/g), and along with the increase of microcrystalline cellulose cellulose content, is the trend of prolongation disintegration.Reason may be that variation has taken place the tablet internal structure, the mutual chimeric compact texture that formed of the particulate concaveconvex shape of microcrystalline Cellulose, and hole is difficult for by moistening tablet by compression failure.Microcrystalline Cellulose is the straight-chain polysaccharide that is made of pyranoid ring D-glucose, and its degree of polymerization is 200, and swellbility is 3.4ml/g, all can use as commercially available Avicel, PH-101, PH-102, PH-103 etc.
Lubricant and fluidizer are selected magnesium stearate, micropowder silica gel etc. for use, and correctives can be selected aspartame, saccharin sodium, stevioside, essence etc. for use, and consumption is 0.1-0.5%.
The present invention is a leading indicator with the disintegration, has done the selection of disintegrating agent carboxymethyl base Starch Sodium and dry adhesive microcrystalline Cellulose consumption.
Test method: the amount weighing supplementary material by the design prescription, sieve, mixing adopts direct powder compression to prepare test specimen, measures the disintegration time of quadrat sampling product everywhere respectively.
The assay method of disintegration is: add 37 ℃ ± 1 ℃ water 2ml in the 10ml graduated cylinder, get 1 oral cavity disintegration tablet, add in the entry, tablet should disintegrate rapidly in water, and the granule after the disintegrate should be able to be by 40 mesh sieves (internal diameter be 441um).6 of recheckings, the disintegrate situation of observing tablet, record complete disintegrate of tablet and granule are by the time of screen cloth.
Test data with the results are shown in Table 1, table 2.
The screening of table 1 microcrystalline Cellulose consumption
| The test lot number | 1 | 2 | 3 | 4 | 5 |
| Tamoxifen Citrate, (g) carboxymethyl starch sodium, (g) microcrystalline Cellulose, (g) micropowder silica gel, (g) magnesium stearate, (g) aspartame, (g) | 1.52 1.5 4.5 0.5 0.1 0.05 | 1.52 1.5 4.0 0.5 0.1 0.04 | 1.52 1.5 3.5 0.5 0.1 0.03 | 1.52 1.5 3.0 0.5 0.1 0.02 | 1.52 1.5 2.5 0.5 0.1 0.01 |
| Disintegration (second) | 97±21 | 57±10 | 45±5 | 48±11 | 65±10 |
| Mouthfeel | No grittiness flavor is too sweet | No grittiness flavor is sweet | No grittiness flavor is sweet | No grittiness good mouthfeel | No grittiness bitter in the mouth |
As can be seen from Table 1, the microcrystalline Cellulose consumption of test lot number 3 is comparatively suitable, selects the consumption of disintegrating agent carboxymethyl base Starch Sodium on this basis, and according to the result of table 1, the consumption of aspartame is adjusted, and test data sees Table 2.
The screening of table 2 disintegrating agent carboxymethyl base Starch Sodium consumption
| The test lot number | 6 | 7 | 8 | 9 | 10 |
| Tamoxifen Citrate, (g) carboxymethyl starch sodium, (g) microcrystalline Cellulose, (g) micropowder silica gel, (g) magnesium stearate, (g) aspartame, (g) | 1.52 0.5 3.5 0.5 0.1 0.02 | 1.52 1.0 3.5 0.5 0.1 0.02 | 1.52 1.5 3.5 0.5 0.1 0.02 | 1.52 2.0 3.5 0.5 0.1 0.02 | 1.52 2.5 3.5 0.5 0.1 0.02 |
| Disintegration (second) | 36±5 | 29±6 | 33±6 | 45±4 | 49±9 |
| Mouthfeel | No grittiness good mouthfeel | No grittiness good mouthfeel | No grittiness good mouthfeel | No grittiness good mouthfeel | No grittiness good mouthfeel |
As can be seen from Table 2, the supplementary product consumption of test lot number 7 is best.
Better for the outward appearance fineness that makes tablet, add a small amount of lactose, its consumption screening sees Table 3.
The screening of table 3 lactose consumption
| The test lot number | 11 | 12 | 13 | 14 | 15 |
| Tamoxifen citrate (g) sodium carboxymethyl starch (g) microcrystalline cellulose (g) superfine silica gel powder (g) dolomol (g) Aspartame (g) lactose (g) | 1.52 0.5 3.5 0.5 0.1 0.02 0.07 | 1.52 1.0 3.5 0.5 0.1 0.02 0.14 | 1.52 1.5 3.5 0.5 0.1 0.02 0.21 | 1.52 2.0 3.5 0.5 0.1 0.02 0.28 | 1.52 2.5 3.5 0.5 0.1 0.02 0.35 |
| Disintegration (second) | 41±3 | 36±5 | 39±4 | 51±6 | 54±11 |
| Mouthfeel | No grittiness good mouthfeel | No grittiness good mouthfeel | No grittiness good mouthfeel | No grittiness good mouthfeel | No grittiness good mouthfeel |
| Tablet appearance | Fineness is good | Fineness is good | Fineness is good | Fineness as | Fineness is good |
As can be seen from Table 3, the adding of lactose can improve the outward appearance of tablet, overall merit, and addition the best of test lot number 12, its disintegration of Tamoxifen Citrate oral cavity disintegration tablet, the mouthfeel that make all adhere to specification.Therefore the present invention is 5.0-10.0wt% by the component content of testing selected carboxymethyl starch sodium, the component content of microcrystalline Cellulose is 45.0-55.0wt%'s, the component content of micropowder silica gel is 5.0-10.0wt%, the component content of magnesium stearate is 1.0-2.0wt%, the component content of lactose is 1.0-3.0wt%, and the component content of aspartame is 0.1-0.5wt%.
In technique of direct powder compression, owing to directly carry out tabletting without the particulate process of preparation, the flowability of powder art and compressibility are the indexs of outbalance, are related to the feasibility of carrying out suitability for industrialized production.If mixed-powder is mobile bad, can have influence on tabletting speed aborning, or the drawbacks such as tablet weight difference is big of compacting; If the compressibility of powder is bad, the tablet mechanical strength of making is not high, and is damaged easily in transportation and storage.In this research, for the flowability and the further checking of test of compressibility of mixed-powder, to guarantee the integrity of tablet in suitability for industrialized production product quality homogeneity, controllability and the Product transport.
Usually with angle of repose of powder as a kind of index of representing powder flowbility, the angle of repose of powder is more little, shows that the flowability of powder is good more.
For verifying repeatability between each batch, prepare 040103,040104,040105 batch sample, measure the indexs such as flowability, compressibility and disintegration of material respectively, see Table 4.
The test of table 43 batch sample physical performance indexs
| Lot number | 040103 | 040104 | 040105 |
| Mixed-powder friability angle of repose test (subtracting weight loss %) disintegration time (second) | 30.5° 1.2 35±4 | 31.2° 1.1 33±4 | 29.8° 1.1 40±5 |
As can be seen from Table 4, the technology of direct powder compression is carried out the preparation of sample, and the mixed-powder of supplementary material has good flowability, and the compressibility of mixed-powder is good, and the tablet that is pressed under less pressure has good hardness.
For further verifying the flowability of material, measure the tablet weight variation of 3 batch samples, see Table 5.
Table 5 tamoxifen oral cavity disintegration tablet weight differential check result
As can be seen from Table 5, the good fluidity of mixed-powder, good reproducibility between each batch, the suitability for industrialized production of suitable direct compression.
Be relatively assay method and the intraoral disintegration situation of disintegration, the oral cavity disintegration tablet of 3 lot numbers carried out volunteer's intraoral disintegration and test,, see Table 6 with the assay method that contrasts external disintegration and the dependency of intraoral disintegration situation.
External disintegration of table 6 and intraoral disintegration time limit
| Lot number | Disintegration (second) | The intraoral disintegration time limit (second) |
| 040206 | 37.3±4.9 | 17.0±1.0 |
| 040207 | 38.0±5.4 | 18.7±0.6 |
| 040208 | 38.3±5.6 | 18.3±0.6 |
As can be seen from Table 6, three batch samples are in external all disintegrates in 1 minute, are equivalent in the oral cavity 20 seconds with interior disintegrate.In the reason of intraoral disintegration time weak point, supposition may be because be disintegrate under the static environment external, and intraoral disintegration has due to the tongue motion.
For showing progressive of the present invention, we have also done the dissolution test of Tamoxifen Citrate oral cavity disintegration tablet of the present invention, and contrast with ordinary tablet.Ordinary tablet is selected from the Tamoxifen Citrate sheet that commercially available Yangtze River Medicine Industry Group Co Ltd, Jiangsu produces, batch number: 030412No.023.Assay method adopts two appendix XC second methods of Chinese Pharmacopoeia version in 2000, is dissolution medium with 0.02mol/L hydrochloric acid solution 1000ml, and rotating speed is that per minute 100 changes, and measures at the 275nm place according to spectrophotography, presses the absorptance (E of tamoxifen
1% 1cm) be 311 calculating, result of the test sees Table 7.
Table 7 Tamoxifen Citrate oral cavity disintegration tablet stripping uniformity test measurement result (%)
| Lot number | Time (minute) | 1 | 2 | 3 | 4 | 5 | 6 | On average ± SD (%) |
| 040206 | 5 10 20 30 45 | 90.0 89.4 97.1 98.7 97.7 | 92.9 95.5 96.8 96.1 96.1 | 85.5 89.7 97.4 98.1 97.7 | 90.0 95.8 96.8 97.4 95.8 | 89.4.9 90.4 93.6 95.5 96.5 | 94.9 96.5 95.2 96.8 97.4 | 90.4±3.2 92.9±3.3 96.1±1.4 97.1±1.2 96.9±0.8 |
| 040207 | 5 10 20 30 45 | 86.8 92.3 95.8 97.4 96.8 | 90.4 92.9 96.1 96.5 94.9 | 88.1 91.3 95.5 97.1 95.8 | 89.1 89.7 92.0 97.7 95.5 | 89.7 91.6 93.2 94.9 94.2 | 92.3 94.2 95.5 96.8 96.5 | 89.4±1.9 92.0±1.5 94.7±1.6 96.7±0.99 95.6±1.0 |
| 040208 | 5 10 20 30 45 | 84.6 90.4 92.6 94.9 97.7 | 93.6 92.9 92.3 96.5 98.1 | 91.0 90.4 92.9 96.8 97.7 | 87.1 90.7 93.6 97.1 96.8 | 90.7 91.6 93.2 96.8 97.7 | 94.5 94.2 95.2 98.4 98.7 | 90.2±3.3 91.7±1.6 93.3±1.0 96.7±1.1 97.8±0.6 |
| The Tamoxifen Citrate ordinary tablet | 5 10 20 30 45 | 31.5 64.6 75.6 81.0 82.0 | 26.4 60.5 78.5 83.0 84.2 | 25.4 66.6 86.8 88.7 88.4 | 18.0 62.1 89.1 80.1 84.6 | 16.7 54.0 85.2 82.3 86.5 | 15.8 54.3 81.7 85.2 86.8 | 22.3±6.4 60.3±5.2 82.8±5.2 83.4±3.1 85.6±2.3 |
According to the regulation of Chinese Pharmacopoeia, the qualified limit of ordinary tablet stripping is to reach 75% of labelled amount in 30 minutes.As can be seen from Table 7, the dissolution homogeneity of the present invention's three batch samples is good, individual variation is little in batch, favorable reproducibility between batch, the all more commercially available ordinary tablet of the dissolution of three batches of oral cavity disintegration tablets is obviously accelerated, dissolution promptly reached more than 89.4% in 5 minutes, had improved 67.1% than the dissolution of ordinary tablet 5 minutes the time.So advantage of the present invention is clearly, its taking convenience, be that a kind of water that do not need in the oral cavity can disintegrate or dissolved tablet, absorb fast, bioavailability is high suitable with oral suspensions, for the old people of dysphagia with gulp down the cancer patient that water is promptly vomitted, and the patient under the special environment that can not obtain water is especially suitable.
The specific embodiment:
The invention will be further described with by way of example more below, provides implementation detail of the present invention, but be not to be intended to limit protection scope of the present invention.
Tamoxifen Citrate, microcrystalline Cellulose, carboxymethyl starch sodium, micropowder silica gel, magnesium stearate, lactose etc. are all crossed 100 mesh sieves.
Take by weighing Tamoxifen Citrate 15.2 grams, earlier with 10 gram carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 35 gram microcrystalline Cellulose, add 1.32 gram lactose, 5 gram micropowder silica gels, 1 gram magnesium stearate and aspartame 0.2 gram then successively, mixing.Detect the percentage composition of Tamoxifen Citrate in the mixed powder, after the calculating sheet was heavy, compacting in flakes.So can suppress 1000 Tamoxifen Citrate oral cavity disintegration tablets.
Its disintegration time is 35 seconds, and dissolution was 93.0% in 15 minutes.
The several examples of following reuse further specify the present invention.Following example is to produce the Formulation Example of 1000 oral cavity disintegration tablets.
Embodiment 1
Tamoxifen Citrate 15.2g
Carboxymethyl starch sodium 6.7g
Little product cellulose 37g
Lactose 2.0g
Micropowder silica gel 5.4g
Magnesium stearate 0.8g
Aspartame 0.2 gram
Make 1000
Tamoxifen Citrate, microcrystalline Cellulose, carboxymethyl starch sodium, micropowder silica gel, magnesium stearate, lactose etc. are all crossed 100 mesh sieves.
Take by weighing Tamoxifen Citrate 15.2 grams, earlier with 6.7 gram carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 37 gram microcrystalline Cellulose, add 2.0 gram lactose, 5.4 gram micropowder silica gels, 0.8 gram magnesium stearate and aspartame 0.2 gram then successively, mixing.Detect the percentage composition of Tamoxifen Citrate in the mixed powder, after the calculating sheet was heavy, compacting in flakes.So can suppress 1000 Tamoxifen Citrate oral cavity disintegration tablets.
Its disintegration time is 38 seconds, and dissolution was 92.3% in 15 minutes.
Embodiment 2
Tamoxifen Citrate 30.4g
Carboxymethyl starch sodium 7g
Microcrystalline Cellulose 35g
Lactose 0.8g
Micropowder silica gel 4.0g
Magnesium stearate 1.2g
Aspartame 0.4 gram
Make 1000
Tamoxifen Citrate, microcrystalline Cellulose, carboxymethyl starch sodium, micropowder silica gel, magnesium stearate, lactose etc. are all crossed 100 mesh sieves.
Take by weighing Tamoxifen Citrate 30.4 grams, earlier with 7 gram carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 35 gram microcrystalline Cellulose, add 0.8 gram lactose, 4.0 gram micropowder silica gels, 1.2 gram magnesium stearate and aspartame 0.4 gram then successively, mixing.Detect the percentage composition of Tamoxifen Citrate in the mixed powder, after the calculating sheet was heavy, compacting in flakes.So can suppress 1000 Tamoxifen Citrate oral cavity disintegration tablets.
Its disintegration time is 40 seconds, and dissolution was 93.2% in 15 minutes.
Embodiment 3
Tamoxifen Citrate 15.2g
Carboxymethyl starch sodium 13.8g
Microcrystalline Cellulose 31.0g
Lactose 0.7g
Micropowder silica gel 6.8g
Magnesium stearate 0.8g
Aspartame 0.2 gram
Make 1000
Tamoxifen Citrate, microcrystalline Cellulose, carboxymethyl starch sodium, micropowder silica gel, magnesium stearate, lactose etc. are all crossed 100 mesh sieves.
Take by weighing Tamoxifen Citrate 15.2 grams, earlier with 13.8 gram carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 31.0 gram microcrystalline Cellulose, add 0.7 gram lactose, 6.8 gram micropowder silica gels, 0.8 gram magnesium stearate and aspartame 0.2 gram then successively, mixing.Detect the percentage composition of Tamoxifen Citrate in the mixed powder, after the calculating sheet was heavy, compacting in flakes.So can suppress 1000 Tamoxifen Citrate oral cavity disintegration tablets.
Its disintegration time is 40 seconds, and dissolution was 92.8% in 15 minutes.
Claims (3)
1. Tamoxifen Citrate oral cavity disintegration tablet, form by Tamoxifen Citrate, disintegrating agent, dry adhesive, filler, fluidizer, lubricant and correctives, the composition content that it is characterized in that said oral cavity disintegration tablet, be by weight percentage: the Tamoxifen Citrate of 20.0-40.0wt%, the carboxymethyl starch sodium of 5.0-10.0wt%, the microcrystalline Cellulose of 45.0-55.0wt%, the micropowder silica gel of 5.0-10.0wt%, the magnesium stearate of 1.0-2.0wt%, the lactose of 1.0-3.0wt%, the aspartame of 0.1-0.5wt%.
2. according to the compound method of the described oral cavity disintegration tablet of claim 1, it is characterized in that comprising following main preparation steps:
(1) Tamoxifen Citrate, microcrystalline Cellulose, carboxymethyl starch sodium, micropowder silica gel, magnesium stearate, lactose, aspartame pulverize separately are crossed 100 mesh sieves;
(2) the first mixing with carboxymethyl starch sodium of Tamoxifen Citrate sieved, mixing, again with the microcrystalline Cellulose mixing, add lactose, micropowder silica gel, magnesium stearate and aspartame more then successively, mix homogeneously, adjustment sheet is heavy to make the described Tamoxifen Citrate oral cavity disintegration tablet of claim 1 with the pressure tabletting.
3. according to the described oral cavity disintegration tablet compound method of claim 2, it is characterized in that adopting direct powder compression.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6245352B1 (en) * | 1999-04-27 | 2001-06-12 | Eli Lilly And Company | Pharmaceutical formulation |
| CN1389199A (en) * | 2002-06-27 | 2003-01-08 | 北京北大药业有限公司 | Slow-releasing Tamoxifen citrate tablet |
| CN1450895A (en) * | 2000-07-06 | 2003-10-22 | 惠氏公司 | Pharmaceutical compositions of estrogenic agents |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6245352B1 (en) * | 1999-04-27 | 2001-06-12 | Eli Lilly And Company | Pharmaceutical formulation |
| CN1450895A (en) * | 2000-07-06 | 2003-10-22 | 惠氏公司 | Pharmaceutical compositions of estrogenic agents |
| CN1389199A (en) * | 2002-06-27 | 2003-01-08 | 北京北大药业有限公司 | Slow-releasing Tamoxifen citrate tablet |
Non-Patent Citations (1)
| Title |
|---|
| 4厂家产枸橼酸他莫昔芬片的溶出度考察. 王瑞芹.中国药房，第13卷第7期. 2002 * |
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