Tablet containing anastrozole as well as application and preparation method of tablet

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to anastrozole-containing tablets, application and a preparation method thereof.The anastrozole-containing tablets are composed of anastrozole, salidroside, glyceryl monostearate, microcrystalline cellulose, xylitol, a disintegrating agent and a lubricant, according to the standard of Chinese Pharmacopoeia 2020 edition, the dissolution rate of the anastrozole-containing tablets in water within 10 min reaches 90% or above, and the dissolution rate of the anastrozole-containing tablets in water within 10 min reaches 90% or above; acceleration tests prove that the content of related substances is low, the tumor cell apoptosis index is remarkably increased in a postmenopausal breast cancer rat model, tumor cell proliferation is effectively inhibited, the synergistic anti-tumor effect is shown, and the pharmaceutical composition is suitable for further application and popularization.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a tablet containing anastrozole, a use thereof and a preparation method thereof. Background Art

[0002] Breast cancer is one of the most common malignant tumors in women worldwide, and its incidence rate is increasing year by year. Especially among elderly women over 65 years old, about 26% will develop breast cancer, and about one-third of the tumor growth depends on high estrogen levels. This type of tumor is called estrogen-dependent breast cancer. Estrogen-dependent breast cancer usually occurs in postmenopausal women. After menopause, the estrogen in women's bodies (such as estradiol and estrone) mainly converts androgens (such as androstenedione and testosterone) from the adrenal glands and ovaries into estrogens through aromatase in peripheral tissues. Inhibiting aromatase and thus reducing the synthesis of estrogen is an effective method for treating postmenopausal estrogen-dependent breast cancer.

[0003] Anastrozole is a highly effective and selective non-steroidal aromatase inhibitor. It is a non-steroidal aromatase inhibitor with the chemical name 2,2'-[5-(1H-1,2,4-Triazol-1-ylmethyl)-1,3-phenylene]bis(2-methylpropa nenitrile). The structural formula is as follows:

[0004]

[0005] The original developer was AstraZeneca, and it was approved by the U.S. FDA in 1995 for the treatment of breast cancer in postmenopausal women. After the patent expired in 2008, many countries around the world approved generic drugs for marketing (such as India, China, Europe, etc.). The current dosage form on the market is tablets.

[0006] Salidroside is an active ingredient extracted from the Rhodiola rosea plant, which has anti-fatigue, anti-oxidation, immunity-enhancing and anti-stress effects. It is often used in the preparation of health products and medicines to help relieve stress, improve physical strength and mental health. The extraction process usually adopts solvent extraction, and after extraction with ethanol or water, salidroside is further separated and purified. It is widely used in traditional medicine and modern health care. As a natural plant extract, it is used to enhance physical strength, improve sleep quality, etc. It has not been found to have a synergistic effect with the anastrozole group to resist tumors.

[0007] As a third-generation aromatase inhibitor, anastrozole plays an important role in the treatment of breast cancer, but its low solubility, bone and joint side effects, and drug resistance limit its long-term use in some patients. Anastrozole has not been used in combination with salidroside and glyceryl monostearate to make tablets. Summary of the invention

[0008] Based on the deficiencies of the prior art, a tablet containing anastrozole is provided, which solves the defects of high content of related substances of anastrozole and low solubility, and is suitable for further expansion of clinical applications.

[0009] Specifically, the inventors solved the problem through the following technical solutions:

[0010] A tablet containing anastrozole, the tablet is composed of anastrozole, salidroside, glyceryl monostearate, microcrystalline cellulose, xylitol, a disintegrant and a lubricant; calculated by weight, specifically as follows:

[0011]

[0012] Furthermore, the microcrystalline cellulose is selected from one or a combination of microcrystalline cellulose V101 and microcrystalline cellulose M112.

[0013] Furthermore, the disintegrant is selected from sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked polyvinyl pyrrolidone. More preferably, the disintegrant is selected from low-substituted hydroxypropyl cellulose.

[0014] Furthermore, the lubricant is selected from one of talc and magnesium stearate; more preferably, the lubricant is selected from magnesium stearate.

[0015] Furthermore, the tablet is composed of anastrozole, salidroside, glyceryl monostearate, microcrystalline cellulose, xylitol, a disintegrant and a lubricant; calculated by weight, specifically as follows:

[0016]

[0017] Furthermore, the tablet preparation process comprises the following steps:

[0018] 1) taking tert-butyl alcohol and adjusting the pH value to 8.0-9.0, adding glyceryl monostearate and salidroside and stirring evenly to obtain a tert-butyl alcohol solution containing the mixture, and setting aside;

[0019] 2) adding anastrozole to the mixed solution, rotary evaporating to dryness, and grinding and sieving to obtain a mixture 1;

[0020] 3) Mix the mixture 1 with colloidal silicon dioxide, microcrystalline cellulose and disintegrant, add the mixture to a wet granulator and stir evenly; add a lubricant and press into tablets to obtain the tablets.

[0021] The weight-to-volume ratio of the tert-butanol is 1:25-45; more preferably, the weight-to-volume ratio of the tert-butanol is 1:35.

[0022] The tablets are composed of anastrozole, salidroside, glyceryl monostearate, microcrystalline cellulose, xylitol, a disintegrant and a lubricant; calculated by weight, specifically as follows:

[0023]

[0024] The preparation process is as follows:

[0025] 1) taking tert-butyl alcohol and adjusting the pH value to 8.5, adding glyceryl monostearate and salidroside and stirring evenly to obtain a tert-butyl alcohol solution containing a mixture, and setting aside; the weight volume ratio of the glyceryl monostearate and salidroside to the tert-butyl alcohol is 1:35;

[0026] 2) adding anastrozole to the mixed solution, rotary evaporating to dryness, and grinding and sieving to obtain a mixture 1;

[0027] 3) Mix the mixture 1 with colloidal silicon dioxide, microcrystalline cellulose and low-substituted hydroxypropyl cellulose and add them to a wet granulator and stir evenly; add magnesium stearate and press into tablets to obtain the product.

[0028] The tablet of the present invention is used in preparing medicine for treating breast cancer.

[0029] Compared with the prior art, the present invention has achieved unexpected technical effects.

[0030] Provided is a tablet of salidroside and anastrozole. The dissolution of the anastrozole tablet in water reaches more than 90% in the 10th minute, which can meet the requirements of the 2020 edition of the Chinese Pharmacopoeia standard. After accelerated experiments, it was found that the content of related substances of anastrozole in Examples 1-3 of the present invention is lower, which is better than other embodiments.

[0031] By adding surfactants such as glyceryl monostearate to improve its solubility in water, and by improving dispersibility and changing dissolution kinetics, the bioavailability of the drug is improved. When salidroside is used in combination with anastrozole, it significantly increases the tumor cell apoptosis index in a postmenopausal breast cancer rat model and effectively inhibits tumor cell proliferation, showing a synergistic anti-tumor effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 : It can be seen from the apoptosis of tumor cells in each group of rats that, compared with the control group, the apoptosis index of each group in the examples and the commercially available group increased (P<0.05), and the increase in the groups in Examples 1-3 was more obvious than that in the groups using each drug alone, and the differences were all statistically significant (P<0.05).

[0033] Figure 2 Comparison of tumor proliferation in each group of rats shows that the proliferation index of Example 1-3 group is significantly lower than that of the control group (P<0.05). The proliferation index of Example 1-3 group is significantly higher than that of Example 1-3 group, and the differences are statistically significant (P<0.05).

[0034] Figure 3 : Comparison of tumor inhibition effects in each group. The tumor growth was slow at the beginning and then grew rapidly in about 5 weeks. The tumor growth delay was observed in each example group, which was significantly different from that in the control group (P<0.05); the tumor inhibition effects of Examples 1-3 were more obvious than those of each single drug (P<0.05), and the tumor growth curve was flat.

[0035] Figure 4 : The four main types of impurities of anastrozole in the accelerated test.

[0036] Figure 5 : The dissolution rate of each embodiment at 0 min, 2 min, 5 min, 10 min, 15 min and 20 min at 0 month.

[0037] Figure 6 : Dissolution of each example at 10 min of the accelerated test at 0, 1, 2, 3, and 6 months.

[0038] Figure 7 : From the comparison of the single impurity content (%) of Examples 1-5 of the present invention and Comparative Examples 1-3 and Comparative Examples 6-7, it can be seen that the single impurity content of the comparative examples is above 0.1% at the 6th month.

[0039] Figure 8 : The total impurity content (%) of Examples 1-5 of the present invention and Comparative Examples 1-3 and Comparative Examples 6-7. It can be seen that the single impurity content of Comparative Examples 1-3 and Comparative Example 6 is above 0.5% at the 6th month.

[0040] Specific embodiment

[0041] The present invention discloses a tablet containing anastrozole, its use and preparation method. Those skilled in the art can refer to the content of this article and appropriately change the process parameters. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through comparative embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0042] Example 1: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0043] Element Weight(g) Anastrozole 1 Salidroside 0.65 Glyceryl Monostearate 0.1 Colloidal Silica 13 Microcrystalline Cellulose V101 100 Xylitol 30 Low substituted hydroxypropyl cellulose 6 Magnesium Stearate 1.35

[0044] Preparation process: Take tert-butanol and adjust the pH value to 8.0, add monostearate glyceryl and salidroside and stir evenly to obtain a tert-butanol solution containing a mixture (the weight volume ratio of the mixture to tert-butanol is 1:25), add anastrozole, rotary evaporate to dryness, grind and sieve to obtain mixture 1; add mixture 1 and microcrystalline cellulose V101, xylitol, cross-linked polyvinyl pyrrolidone and colloidal silicon dioxide into a wet granulator and stir evenly; add magnesium stearate and press into tablets, and finally prepare tablets.

[0045] The stirring speed of the wet granulator was 250 rpm, the cutting speed was 300 rpm, and the mixing was performed for 5 minutes.

[0046] Example 2: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0047]

[0048]

[0049] Preparation process: Take tert-butanol and adjust the pH value to 9.0, add monostearate glyceryl and salidroside and stir evenly to obtain a tert-butanol solution containing a mixture (the weight volume ratio of the mixture to tert-butanol is 1:45), add anastrozole, rotary evaporate to dryness, grind and sieve to obtain mixture 1; add mixture 1 and microcrystalline cellulose V101, xylitol, cross-linked polyvinyl pyrrolidone and colloidal silicon dioxide into a wet granulator and stir evenly; add magnesium stearate and press into tablets, and finally prepare tablets.

[0050] The stirring speed of the wet granulator was 250 rpm, the cutting speed was 300 rpm, and the mixing was performed for 5 minutes.

[0051] Example 3: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0052] Element Weight(g) Anastrozole 1 Salidroside 0.95 Glyceryl Monostearate 0.3 Colloidal Silica 41 Microcrystalline Cellulose V101 135 Xylitol 45 Low substituted hydroxypropyl cellulose 10 Magnesium Stearate 1.95

[0053] Preparation process: Take tert-butanol and adjust the pH value to 8.5, add monostearate glyceryl and salidroside and stir evenly to obtain a tert-butanol solution containing a mixture (the weight volume ratio of the mixture to tert-butanol is 1:35), add anastrozole, rotary evaporate to dryness, grind and sieve to obtain mixture 1; add mixture 1 and microcrystalline cellulose V101, xylitol, cross-linked polyvinyl pyrrolidone and colloidal silicon dioxide into a wet granulator and stir evenly; add magnesium stearate and press into tablets, and finally prepare tablets.

[0054] The stirring speed of the wet granulator was 250 rpm, the cutting speed was 300 rpm, and the mixing was performed for 5 minutes.

[0055] Example 4: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0056] Element Weight(g) Anastrozole 1 Salidroside 0.65 Glyceryl Monostearate 0.1 Colloidal Silica 13 Microcrystalline Cellulose V101 50 Microcrystalline Cellulose M112 50 Xylitol 30 Sodium carboxymethyl starch 6 talcum powder 1.35

[0057] The preparation process is the same as that of Example 3.

[0058] Example 5: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0059] Element Weight(g) Anastrozole 1 Salidroside 0.65 Glyceryl Monostearate 0.1 Colloidal Silica 13 Microcrystalline Cellulose M112 100 Xylitol 30 Low substituted hydroxypropyl cellulose 6 Magnesium Stearate 1.35

[0060] The preparation process is the same as that of Example 3.

[0061] Comparative Example 1: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0062]

[0063]

[0064] The preparation process is the same as that of Example 3.

[0065] Comparative Example 2: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0066] Element Weight(g) Anastrozole 1 Salidroside 0.95 Colloidal Silica 41 Microcrystalline Cellulose V101 135 Xylitol 45 Low substituted hydroxypropyl cellulose 10 Magnesium Stearate 1.95

[0067] The preparation process is the same as that of Example 3.

[0068] Comparative Example 3: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0069] Element Weight(g) Anastrozole 1 Salidroside 2 Glyceryl Monostearate 0.05 Colloidal Silica 70 Microcrystalline Cellulose 101 50 Xylitol 100 Low substituted hydroxypropyl cellulose 10 Magnesium Stearate 2

[0070] The preparation process is the same as that of Example 3.

[0071] Comparative Example 4: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0072] Element Weight(g) Anastrozole 1 Salidroside 0.95 Glyceryl Monostearate 0.3 Colloidal Silica 41 lactose 135 Xylitol 45 Low substituted hydroxypropyl cellulose 10 Magnesium Stearate 1.95

[0073] The preparation process is the same as that of Example 3.

[0074] Comparative Example 5: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0075] Element Weight(g) Anastrozole 1 Salidroside 0.95 Glyceryl Monostearate 0.3 Colloidal Silica 41 Microcrystalline Cellulose V101 135 Xylitol 45 Low substituted hydroxypropyl cellulose 10 Magnesium Stearate 1.95

[0076] The preparation process is the same as that of Example 3.

[0077] Comparative Example 6: A tablet containing anastrozole and a preparation method thereof: 1000 tablets

[0078]

[0079]

[0080] The preparation process is the same as that of Example 3.

[0081] Preparation process: Take ethanol and adjust the pH value to 3.5, add anastrozole, rotate and evaporate to dryness, grind and sieve, add monostearate glyceryl, salidroside microcrystalline cellulose V101, xylitol, cross-linked polyvinyl pyrrolidone and colloidal silicon dioxide into a wet granulator and stir evenly; add magnesium stearate and press into tablets, and finally prepare tablets.

[0082] The stirring speed of the wet granulator was 250 rpm, the cutting speed was 300 rpm, and the mixing was performed for 5 minutes.

[0083] Comparative Example 7: Commercially available product: National Medicine Standard No. H20050328.

[0084] 1. Pharmacological Experiment: Effect of the Drugs of the Embodiments of the Present Invention on the Growth of Breast Cancer in Postmenopausal Rats

[0085] 1. Establishment and grouping of postmenopausal breast cancer rat model:

[0086] The preparation of the postmenopausal breast cancer rat model was based on the literature [Kang XM, Jin S, Zhang QY. Antitumor and anti-an-giogenic activity of soy phytoestrogen on 7, 12-Dimeth-ylbenz[a]anthracene-induced mammary tumors following ovariectomy in Sprague-Dawley rats [J]. J Food Sci, 2009, 74 (7): H237-H242.],

[0087] Sixty six-week-old female Sprague-Dawley rats were fed with a basic diet for one week, and then each rat was gavaged with 1 mL corn oil containing 20 mg of the carcinogen DMBA. The rats were fed with the modified AIN-93G standard diet using corn oil instead of soybean oil to minimize the effect of exogenous phytoestrogens. After six weeks of exposure to the carcinogen, tumors were palpable. When the tumors grew to an acceptable size (300-400 mm3), the rats were bilaterally ovarian removed and randomly divided into a control group (1 mL 0.9% sodium chloride), Example 1 group, Example 2 group, Example 3 group, Comparative Example 1, and a commercially available anastrozole group [dosage: 0.1 mg / (kg·d) dissolved in 1 mL 0.9% sodium chloride] for gavage administration. In terms of anastrozole, 0.1 mg of anastrozole was dissolved in 1 ml of 0.9% sodium chloride, with 10 rats in each group. The rats were fed by gavage every day until the experiment was terminated after 20 weeks of exposure to the carcinogen. Blood was collected by cardiac puncture and centrifuged at 1000 r / min for 10 min to obtain plasma, which was stored at -80°C. All tumor specimens were weighed within 24 h after resection and fixed in 10% formalin, embedded in paraffin, and sliced.

[0088] 2. Result detection

[0089] 2.1 Tumor cell apoptosis detection

[0090] Under the action of terminal deoxyribonucleotidyl transferase (TdT Enzyme), fluorescein-labeled dUTP can connect to the 3'-OH end of the broken DNA in apoptotic cells. According to the instructions of the TUNEL cell apoptosis detection kit, the breakage of nuclear DNA in the process of apoptosis is detected. The apoptotic index is calculated as the percentage of positive cells to the total number of cells. For each tumor, 1000 cells are counted.

[0091] 2.2 Tumor cell proliferation assay

[0092] Cell proliferation was detected by BrdU immunohistochemistry. Each mouse was given 50 mg BrdU / kg intraperitoneally 2 h before being killed. The nuclei labeled with BrdU were recognized by anti-BrdU antibodies. The cell proliferation index was calculated as the percentage of labeled cells to the total number of cells. 1000 cells were counted for each tumor.

[0093] 2.3 Tumor inhibition test

[0094] The long and short diameters of the tumor were measured every 2 weeks for 12 consecutive weeks, and the tumor volume was calculated (formula: V = short diameter 2 × long diameter / 2), and the tumor growth curves of each group were drawn.

[0095] 3. Statistical Analysis

[0096] Graphpad Prism 9.0 software was used for data processing, and the measured data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among multiple groups, and SNK-q was used for pairwise comparison among groups. The difference was considered statistically significant when P < 0.05.

[0097] 4. Results

[0098] 4.1 Tumor cell apoptosis detection and tumor cell proliferation assay

[0099] Apoptosis of tumor cells in rats in each group Figure 1 Compared with proliferation Figure 2 It can be seen that compared with the control group, the apoptosis index of each group in the examples and the commercially available group increased (P<0.05), and the treatment group of Example 1 increased more significantly than the groups using the drug alone (P<0.05); the proliferation index of the groups of Examples 1-3 was significantly lower than that of the control group (P<0.05). Compared with the groups of Examples 1-3, the apoptosis index of Comparative Example 1 and the commercially available product (Comparative Example 7) was lower (P<0.05), and the proliferation index was significantly increased, and the differences were statistically significant (P<0.05).

[0100] 4.2 Tumor inhibition test

[0101] Comparison of tumor inhibition effects among groups ( Figure 3 ) The tumors in each group started to grow slowly, and then grew rapidly in about 5 weeks. The tumor growth delay was observed in each example group, which was significantly different from the tumor growth in the control group (P<0.05); the tumor inhibition effect of Examples 1-3 was more obvious than that of each commercially available product (Comparative Example 7) and Comparative Example 1 (P<0.05), and the tumor growth curve was flat.

[0102] 2. Physical performance testing

[0103] Table 1 Physical properties test results of each embodiment

[0104]

[0105] Reference for dissolution and related substances testing (General Rules of Part Four of the 2020 Edition of the Chinese Pharmacopoeia)

[0106] [Related substance inspection] Determined according to high performance liquid chromatography (General Rule 0512).

[0107] Take an appropriate amount of the product in the test solution, dissolve it in mobile phase A and dilute it to make a solution containing about 2 mg per 1 ml.

[0108] For the control solution, accurately measure an appropriate amount of the test solution and quantitatively dilute it with mobile phase A to make a solution containing 4 μg per 1 ml.

[0109] System suitability solution: Take appropriate amounts of anastrozole, impurity I reference substance and impurity IV reference substance, dissolve in mobile phase A and dilute to make a solution containing approximately 1 mg of anastrozole, 10 μg of impurity I and 10 μg of impurity IV per 1 ml.

[0110] Chromatographic conditions: using octadecylsilane bonded silica gel as filler (Ultimate XB-C column, 4.6mmX250mm, 5μm or equivalent performance column); mobile phase A is acetonitrile-water (40:60), mobile phase B is acetonitrile-water (60:40), linear gradient elution is performed according to the following table; flow rate is 1.0ml per minute; column temperature is 35℃; detection wavelength is 215nm; injection volume is 10μl. Gradient elution is performed according to the following Table 2.

[0111] Table 2

[0112]

[0113] Determination method: Precisely measure the test solution and the control solution, inject them into the liquid chromatograph respectively, and record the chromatogram. If there are chromatographic peaks with the same retention time as impurity II (relative retention time is about 0.8) and impurity I (relative retention time is about 1.2) in the chromatogram of the limit test solution, their peak areas shall not be greater than the main peak area of ​​the control solution (0.2%), and the peak area of ​​other single impurity peaks shall not be greater than 0.5 times (0.1%) of the main peak area of ​​the control solution, and the sum of the peak areas of each impurity shall not be greater than 2.5 times (0.5%) of the main peak area of ​​the control solution. Peaks less than 0.1 times the main peak area of ​​the control solution shall be ignored.

[0114] [Dissolution test] Dissolution and release test method (General Chapter 0931 Method 2 of the 2020 edition of the "Chinese Pharmacopoeia") was used for determination.

[0115] The dissolution conditions were 900 ml of water as solvent and a rotation speed of 50 revolutions per minute. The operation was carried out according to the law and samples were taken after 30 minutes.

[0116] Take an appropriate amount of the dissolution solution of the test sample, filter it, and take the filtrate.

[0117] Reference solution: Take an appropriate amount of anastrozole reference substance, weigh it accurately, add an appropriate amount of acetonitrile to dissolve it, and add water to quantitatively dilute it to make a solution containing about 1.1 μg per 1 ml.

[0118] Chromatographic conditions: octadecylsilane bonded silica gel was used as filler (Ultimate XB-C column, 4.6 mmX250 mm, 5 μm or equivalent performance column); mobile phase A was acetonitrile-water (40:60), mobile phase B was acetonitrile-water (60:40), linear gradient elution was performed according to the following table; flow rate was 1.0 ml per minute; column temperature was 35°C; detection wavelength was 215 nm; injection volume was 100 μl.

[0119] System suitability solution: Take appropriate amounts of anastrozole, impurity I reference substance and impurity IV reference substance, dissolve in mobile phase A and dilute to make a solution containing approximately 1 mg of anastrozole, 10 μg of impurity I and 10 μg of impurity IV per 1 ml.

[0120] The determination method is shown under the content determination item. Calculate the dissolution amount of each tablet. The limit is 85% of the labeled amount, which should comply with the regulations.

[0121] result

[0122] Figure 4 : The four main types of impurities of anastrozole in the accelerated test.

[0123] Figure 5 : The cumulative release of Examples 1-4 of the present invention and Comparative Examples 3-7 at 0 min, 2 min, 5 min, 10 min, 15 min, and 20 min at 0 month, the dissolution medium is water. It can be seen that the dissolution curves of Examples 1-4 are significantly higher than those of Comparative Examples 3-7, and the final dissolution examples are also lower than those of the Comparative Examples.

[0124] Figure 6 : Dissolution of each example at 10 min of the accelerated test at 0, 1, 2, 3, and 6 months.

[0125] Figure 7 : From the comparison of the single impurity content (%) of Examples 1-5 of the present invention and Comparative Examples 1-3 and Comparative Examples 6-7, it can be seen that the single impurity content of the comparative examples is above 0.1% at the 6th month.

[0126] Figure 8 : The total impurity content (%) of Examples 1-5 of the present invention and Comparative Examples 1-3 and Comparative Examples 6-7. It can be seen that the single impurity content of Comparative Examples 1-3 and Comparative Example 6 is above 0.5% at the 6th month.

Claims

1. A tablet containing anastrozole, characterized in that The tablets are composed of anastrozole, salidroside, glyceryl monostearate, microcrystalline cellulose, xylitol, a disintegrant and a lubricant; calculated by weight, specifically as follows:

2. The tablet according to claim 1, characterized in that The microcrystalline cellulose is selected from one or a combination of microcrystalline cellulose V101 and microcrystalline cellulose M112.

3. The tablet according to claim 1, characterized in that The disintegrant is selected from sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked polyvinyl pyrrolidone. More preferably, the disintegrant is selected from low-substituted hydroxypropyl cellulose.

4. The tablet according to claim 1, characterized in that The lubricant is selected from talc and magnesium stearate; more preferably, the lubricant is selected from magnesium stearate.

5. The tablet according to claim 1, characterized in that The tablets are composed of anastrozole, salidroside, glyceryl monostearate, microcrystalline cellulose, xylitol, a disintegrant and a lubricant; calculated by weight, specifically as follows:

6. The tablet according to claim 1, characterized in that The tablet preparation process comprises the following steps: 1) taking tert-butyl alcohol and adjusting the pH value to 8.0-9.0, adding glyceryl monostearate and salidroside and stirring evenly to obtain a tert-butyl alcohol solution containing the mixture, and setting aside; 2) adding anastrozole to the mixed solution, rotary evaporating to dryness, and grinding and sieving to obtain a mixture 1; 3) Mix the mixture 1 with colloidal silicon dioxide, microcrystalline cellulose and disintegrant, add the mixture to a wet granulator and stir evenly; add a lubricant and press into tablets to obtain the tablets.

7. The tablet according to claim 6, characterized in that The weight volume ratio of the tert-butyl alcohol is 1:25-45; More preferably, the weight-to-volume ratio of the tert-butyl alcohol is 1:

35.

8. The tablet according to claim 1, characterized in that The tablets are composed of anastrozole, salidroside, glyceryl monostearate, microcrystalline cellulose, xylitol, a disintegrant and a lubricant; calculated by weight, specifically as follows: The preparation process is as follows: 1) taking tert-butyl alcohol and adjusting the pH value to 8.5, adding glyceryl monostearate and salidroside and stirring evenly to obtain a tert-butyl alcohol solution containing a mixture, and setting aside; the weight volume ratio of the glyceryl monostearate and salidroside to the tert-butyl alcohol is 1:35; 2) adding anastrozole to the mixed solution, rotary evaporating to dryness, and grinding and sieving to obtain a mixture 1; 3) Mix the mixture 1 with colloidal silicon dioxide, microcrystalline cellulose and low-substituted hydroxypropyl cellulose and add them to a wet granulator and stir evenly; add magnesium stearate and press into tablets to obtain the product.

9. Use of the tablet according to any one of claims 1 to 8 in the preparation of a drug for treating breast cancer.

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