CN103860486A - Letrozole orally disintegrating tablets and preparation method - Google Patents
Letrozole orally disintegrating tablets and preparation method Download PDFInfo
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- CN103860486A CN103860486A CN201210524897.9A CN201210524897A CN103860486A CN 103860486 A CN103860486 A CN 103860486A CN 201210524897 A CN201210524897 A CN 201210524897A CN 103860486 A CN103860486 A CN 103860486A
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- letrozole
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- sorbitol
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Abstract
The invention belongs to the medicine technical field, and more specifically relates to a letrozole orally disintegrating tablets and a preparation method. The letrozole orally disintegrating tablets comprise a main component letrozole and an auxiliary component such as a disintegrating agent, a filler and a flavouring. The letrozole orally disintegrating tablets have the advantages that disintegration or dissolving can be carried out in oral cavity without water, and have the characteristics of convenient administration, fast absorption and high biology availability, according to the letrozole orally disintegrating tablets and the preparation method, the compliance of drug application for patients can be increased, and the selection of the clinical drug application for different patients can be increased.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of letrozole oral cavity disintegration tablet, also relate to the preparation method of above-mentioned oral cavity disintegration tablet, above-mentioned letrozole oral cavity disintegration tablet is for the treatment of breast in postmenopausal women cancer invalid after tamoxifen and other estrogen antagonist therapy for treating.
Background technology
Breast carcinoma is one of main tumor threatening WomanHealth, and its sickness rate accounts for 30% of Cancer Mortality, and mortality rate accounts for 15%.Clinical statistics demonstration, the sickness rate of breast carcinoma has the development tendency of rejuvenation, urban-rural integration, and pre-preventing and controlling are shouldered heavy responsibilities.
Letrozole is the benzyl triazole derivative of synthetic, is developed by Switzerland's Novartis, within 1996, goes on the market first, within 1997, go on the market in the U.S. in Britain.Two (4-cyano-phenyl) methyl of chemical name: 1-[]-1,2,4 ,-triazole, chemical formula is:
Letrozole is novel high selectivity arimedex, by suppressing aromatase, makes decrease in estrogen, thereby eliminates the stimulation of estrogen to tumor growth.The activity in vivo of letrozole than first generation arimedex aminoglutethimide 150-25 doubly.It is strong that clinical research proves that letrozole has antitumor action, and specificity is high, and toxicity is few.
Between in April, 1998～2000 year April, the international breast carcinoma cooperative groups of letrozole is accepted local late period or metastatic breast cancer patient 907 examples after menopause altogether for medical treatment.This large sample is from the multicenter double blinding III clinical trial phase object of observation at 29 national 201Ge centers.Patient is divided into two groups at random, accepts letrozole therapist 453 examples (letrozole group), every days 2.5 mg.Accept tamoxifen therapist 454 examples (tamoxifen group), every day 20mg.Total effective rate demonstration, letrozole is better than tamoxifen (P<0.001).The toleration of two medicines is all good.This group result shows, postmenopausal women with advanced patient with breast cancer letrozole is obviously better than to tamoxifen as the curative effect of first-line treatment, should serve as first-selected Therapeutic Method.
Oral cavity disintegration tablet (orally disintegrating tablets), is called for short oral cavity disintegration tablet, is that a kind of water that do not need in oral cavity can disintegrate or the tablet of dissolving.The preparation characteristic of oral cavity disintegration tablet is: do not need water or only need use a small amount of water, also without chewing, medicine is placed in oral cavity, meet after the rapid dissolving of saliva or disintegrate, absorb rear onset along with autonomous and involuntary swallowing act of user enters digestive system, be particularly useful for the patient's medication under the special environments such as old man, child, dysphagia or drinking-water inconvenience.Compared with conventional tablet, the advantage of oral cavity disintegration tablet is: rapid-action, bioavailability is high, taking convenience, and reducing medicine stimulates esophagus and gastrointestinal.
The development of oral cavity disintegration tablet starts from late 1970s, has the features such as rapid-action, taking convenience due to it, and existing this veriety of dozens of goes on the market in various countries at present.China SFDA is using oral cavity disintegration tablet as a kind of novel form, and national Yao Shen has accepted at center the application of more than 300 this kind, and this market is developing growth rapidly.
Summary of the invention
The object of this invention is to provide a kind of letrozole oral cavity disintegration tablet and preparation method thereof.
Letrozole oral cavity disintegration tablet of the present invention is made up of the supplementary material medicine of following weight portion:
Letrozole 100, lactose 44-68, sorbitol 128-152, microcrystalline Cellulose 104-128, low-substituted hydroxypropyl cellulose 20-24, saccharin sodium 0.8-2, magnesium stearate 4-5.6.
Preferably, medicine of the present invention is to be made up of the supplementary material medicine of following weight ratio:
Letrozole 100, lactose 44, sorbitol 128, microcrystalline Cellulose 104, low-substituted hydroxypropyl cellulose 20, saccharin sodium 0.8, magnesium stearate 4.
Or: letrozole 100, lactose 68, sorbitol 152, microcrystalline Cellulose 128, low-substituted hydroxypropyl cellulose 24, saccharin sodium 2, magnesium stearate 5.6.
Or: letrozole 100, lactose 56, sorbitol 140, microcrystalline Cellulose 116, low-substituted hydroxypropyl cellulose 22, saccharin sodium 1.4, magnesium stearate 4.8.
Another object of the present invention is to provide the preparation method of this letrozole oral cavity disintegration tablet, and preparation method is as follows:
(1) letrozole, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, sorbitol, magnesium stearate are dried 1 hour in 115 ° of C, pulverize 100 mesh sieves, and it is for subsequent use that lactose and saccharin sodium were pulverized 100 mesh sieves;
(2) take in proportion the low-substituted hydroxypropyl cellulose of letrozole, sorbitol, lactose, saccharin sodium, 1/3 amount, the microcrystalline Cellulose mixing of 1/3 amount, obtain mixed material;
(3) in step (2) gained mixed material, add 50% alcoholic solution, make suitable soft material, granulate with 32 mesh sieves, wet grain is dry in 40 ± 5 ° of C, with 32 mesh sieve granulate;
(4) step (3) gained granule is mixed homogeneously with the microcrystalline Cellulose of surplus, the low-substituted hydroxypropyl cellulose of surplus, the magnesium stearate of proportional quantities; Semi-finished product chemical examinations, tabletting and get final product.
The supplementary material part by weight of letrozole oral cavity disintegration tablet of the present invention and preparation method are through a large amount of strict screening tests, process certification, after stability study, obtain, through screening test, process certification, stability study proved invention supplementary material ratio is reasonable, stable preparation process, finished product preparation is stable, meets the preparation guideline requirement for oral cavity disintegration tablet of galenic pharmacy and State Food and Drug Administration.
After letrozole orally disintegrating tablet preparation of the present invention completes, carry out quality research, work out the method for inspection of indices, and carry out the methodology checking of each index detection method according to the guideline of Chinese Pharmacopoeia and new drug research, all methods all meet analysis of pharmaceutical dosage forms requirement, according to these methods, the letrozole oral cavity disintegration tablet of development are detected and are studied.
Detailed description of the invention
Embodiment 1
Supplementary material weight ratio is: letrozole 100, lactose 56, sorbitol 140, microcrystalline Cellulose 116, low-substituted hydroxypropyl cellulose 22, saccharin sodium 1.4, magnesium stearate 4.8.
Preparation method:
(1) letrozole, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, sorbitol, magnesium stearate are dried 1 hour in 115 ° of C, pulverize 100 mesh sieves, and it is for subsequent use that lactose and saccharin sodium were pulverized 100 mesh sieves;
(2) take in proportion the low-substituted hydroxypropyl cellulose of letrozole, sorbitol, lactose, saccharin sodium, 1/3 amount, the microcrystalline Cellulose mixing of 1/3 amount, obtain mixed material;
(3) in step (2) gained mixed material, add 50% alcoholic solution, make suitable soft material, granulate with 32 mesh sieves, wet grain is dry in 40 ± 5 ° of C, with 32 mesh sieve granulate;
(4) step (3) gained granule is mixed homogeneously with the microcrystalline Cellulose of surplus, the low-substituted hydroxypropyl cellulose of surplus, the magnesium stearate of proportional quantities; Semi-finished product chemical examinations, tabletting and get final product.
Assay: outward appearance: white tablets; Tablet weight variation: conform with the regulations; Disintegration and leach dynamics: conform with the regulations; Dissolution: 99.00%; Related substance: 0.23%; Content: 99.85%.
Embodiment 2
Supplementary material weight ratio is: letrozole 100, lactose 44, sorbitol 128, microcrystalline Cellulose 104, low-substituted hydroxypropyl cellulose 20, saccharin sodium 0.8, magnesium stearate 4.
Preparation method:
(1) letrozole, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, sorbitol, magnesium stearate are dried 1 hour in 115 ° of C, pulverize 100 mesh sieves, and it is for subsequent use that lactose and saccharin sodium were pulverized 100 mesh sieves;
(2) take in proportion the low-substituted hydroxypropyl cellulose of letrozole, sorbitol, lactose, saccharin sodium, 1/3 amount, the microcrystalline Cellulose mixing of 1/3 amount, obtain mixed material;
(3) in step (2) gained mixed material, add 50% alcoholic solution, make suitable soft material, granulate with 32 mesh sieves, wet grain is dry in 40 ± 5 ° of C, with 32 mesh sieve granulate;
(4) step (3) gained granule is mixed homogeneously with the microcrystalline Cellulose of surplus, the low-substituted hydroxypropyl cellulose of surplus, the magnesium stearate of proportional quantities; Semi-finished product chemical examinations, tabletting and get final product.
Assay: outward appearance: white tablets; Tablet weight variation: conform with the regulations; Disintegration and leach dynamics: conform with the regulations; Dissolution: 99.35%; Related substance: 0.26%; Content: 99.36%.
Embodiment 3
Supplementary material weight ratio is: letrozole 100, lactose 68, sorbitol 152, microcrystalline Cellulose 128, low-substituted hydroxypropyl cellulose 24, saccharin sodium 2, magnesium stearate 5.6.
Preparation method:
(1) letrozole, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, sorbitol, magnesium stearate are dried 1 hour in 115 ° of C, pulverize 100 mesh sieves, and it is for subsequent use that lactose and saccharin sodium were pulverized 100 mesh sieves;
(2) take in proportion the low-substituted hydroxypropyl cellulose of letrozole, sorbitol, lactose, saccharin sodium, 1/3 amount, the microcrystalline Cellulose mixing of 1/3 amount, obtain mixed material;
(3) in step (2) gained mixed material, add 50% alcoholic solution, make suitable soft material, granulate with 32 mesh sieves, wet grain is dry in 40 ± 5 ° of C, with 32 mesh sieve granulate;
(4) step (3) gained granule is mixed homogeneously with the microcrystalline Cellulose of surplus, the low-substituted hydroxypropyl cellulose of surplus, the magnesium stearate of proportional quantities; Semi-finished product chemical examinations, tabletting and get final product.
Assay: outward appearance: white tablets; Tablet weight variation: conform with the regulations; Disintegration and leach dynamics: conform with the regulations; Dissolution: 99.10%; Related substance: 0.28%; Content: 99.65%.
Repeat sample assay: according to supplementary material formula and the preparation method of embodiment 1, repeat to prepare three batch samples in a small amount, its quality index is tested, result all conforms with the regulations, inspection detailed results is in table 1.
Table 1 repeats sample assay
Repeated trials confirmation, this prescription is reasonable, and this technique is more stable, can prepare the oral cavity disintegration tablet conforming to quality requirements, and can amplify this technique, further investigates stability and prescription.
[0020] influence factor test: for test sample carries out influence factor's test, experimental condition is 60 DEG C of high temperature taking 100311 batches, 75% high humidity, 4500Lx illumination, go mensuration respectively at 0 day, 5 days, 10 days, and result of the test is in table 2.
Table 2 influence factor result of the test
Conclusion: influence factor's result of the test shows, this product formulation and technology is reasonable, and product is stable.Compound oral cavity disintegration tablet standard.
Get three batch samples and carry out accelerated test 6 months, experimental condition is to place 6 months under 40 DEG C of temperature and relative humidity 75% ± 5% condition, and assay is in table 3.
6 months assays of table 3 three batch sample accelerated tests
The assay that three batch samples keep sample 24 months for a long time, under commercially available product terms of packing, room temperature is placed the assay after 24 months naturally, in table 4.
Table 4 24 months assays that keep sample for a long time
Can be found out by table 3 and table 4 result, letrozole oral cavity disintegration tablet of the present invention indices under extreme storage condition and room temperature nature still conforms with the regulations.Prove letrozole orally disintegrating tablet preparation prescription rationally with this, process stabilizing, is suitable for producing.
Claims (5)
1. a letrozole oral cavity disintegration tablet, is characterized in that this medicine supplementary material weight ratio is: letrozole 100, lactose 44-68, sorbitol 128-152, microcrystalline Cellulose 104-128, low-substituted hydroxypropyl cellulose 20-24, saccharin sodium 0.8-2, magnesium stearate 4-5.6.
2. letrozole oral cavity disintegration tablet according to claim 1, is characterized in that the supplementary material weight ratio of this medicine is: letrozole 100, lactose 44, sorbitol 128, microcrystalline Cellulose 104, low-substituted hydroxypropyl cellulose 20, saccharin sodium 0.8, magnesium stearate 4.
3. letrozole oral cavity disintegration tablet according to claim 1, is characterized in that the supplementary material weight ratio of this medicine is: letrozole 100, lactose 68, sorbitol 152, microcrystalline Cellulose 128, low-substituted hydroxypropyl cellulose 24, saccharin sodium 2, magnesium stearate 5.6.
4. letrozole oral cavity disintegration tablet according to claim 1, is characterized in that the supplementary material weight ratio of this medicine is: letrozole 100, lactose 56, sorbitol 140, microcrystalline Cellulose 116, low-substituted hydroxypropyl cellulose 22, saccharin sodium 1.4, magnesium stearate 4.8.
5. according to the preparation method of the letrozole oral cavity disintegration tablet described in claim 1-4 any one, it is characterized in that this letrozole oral cavity disintegration tablet makes through following steps:
(1) letrozole, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, sorbitol, magnesium stearate are dried 1 hour in 115 ° of C, pulverize 100 mesh sieves, and it is for subsequent use that lactose and saccharin sodium were pulverized 100 mesh sieves;
(2) take in proportion the low-substituted hydroxypropyl cellulose of letrozole, sorbitol, lactose, saccharin sodium, 1/3 amount, the microcrystalline Cellulose mixing of 1/3 amount, obtain mixed material;
(3) in step (2) gained mixed material, add 50% alcoholic solution, make suitable soft material, granulate with 32 mesh sieves, wet grain is dry in 40 ± 5 ° of C, with 32 mesh sieve granulate;
(4) step (3) gained granule is mixed homogeneously with the microcrystalline Cellulose of surplus, the low-substituted hydroxypropyl cellulose of surplus, the magnesium stearate of proportional quantities; Semi-finished product chemical examinations, tabletting and get final product.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210524897.9A CN103860486B (en) | 2012-12-10 | 2012-12-10 | A kind of Lelrozol orally-disintegratintablet tablet and preparation method thereof |
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| CN201210524897.9A CN103860486B (en) | 2012-12-10 | 2012-12-10 | A kind of Lelrozol orally-disintegratintablet tablet and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106983727B (en) * | 2017-05-27 | 2020-04-14 | 江苏苏南药业实业有限公司 | Letrozole tablet and preparation method thereof |
| CN111012752A (en) * | 2019-12-31 | 2020-04-17 | 瀚晖制药有限公司 | Letrozole tablet and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085191A (en) * | 2009-12-08 | 2011-06-08 | 北京以岭生物工程有限公司 | Anastrozole oral disintegrating tablet and preparation method thereof |
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- 2012-12-10 CN CN201210524897.9A patent/CN103860486B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085191A (en) * | 2009-12-08 | 2011-06-08 | 北京以岭生物工程有限公司 | Anastrozole oral disintegrating tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 吴春丽等: ""高效液相色谱法测定来曲唑口腔崩解片的含量及均匀度"", 《中国医院药学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106983727B (en) * | 2017-05-27 | 2020-04-14 | 江苏苏南药业实业有限公司 | Letrozole tablet and preparation method thereof |
| CN111012752A (en) * | 2019-12-31 | 2020-04-17 | 瀚晖制药有限公司 | Letrozole tablet and preparation method thereof |
| CN111012752B (en) * | 2019-12-31 | 2020-09-01 | 瀚晖制药有限公司 | Letrozole tablet and preparation method thereof |
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| CN103860486B (en) | 2016-06-15 |
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