A tablet containing meloxicam and a method for preparing the same

Abstract

The application relates to the technical field of pharmaceutical compositions, in particular to a meloxicam-containing tablet and a preparation method thereof, wherein the meloxicam-containing tablet comprises the following components in parts by weight: component A is 11-34 parts, starch is 30-60 parts, dextrin is 20-40 parts, and a lubricant is 0.02-0.2 parts. The component A comprises meloxicam 1-4 parts and glucose 10-30 parts, the particle size of the meloxicam is 20-30 microns, and the particle size of the glucose is 50-100 microns. According to the technical scheme, the meloxicam and the glucose are prepared into the component A, and then are mixed with other starch, dextrin and other auxiliary materials, so that the solubility of the meloxicam tablet is obviously improved, and the bioavailability is improved.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical composition technology, and more specifically, to a meloxicam-containing tablet and a method for preparing the same. Background Technology

[0002] Meloxicam is a nonsteroidal anti-inflammatory drug that can be used in animal husbandry and pet breeding. It is widely used to treat joint swelling and pain caused by arthritis, and to relieve pain after orthopedic or soft tissue surgery, with significant efficacy.

[0003] However, meloxicam has poor water solubility, often resulting in low bioavailability of meloxicam formulations. Although existing technologies have developed meloxicam oral solutions and other formulations that have solved the water solubility problem to some extent, their preparation costs are high, and they are inconvenient to transport and administer.

[0004] Therefore, there is an urgent need in the field for a meloxicam-containing tablet and its preparation method to solve the above problems, hence this application is filed. Summary of the Invention

[0005] The purpose of this application is to provide a meloxicam-containing tablet and a method for preparing the same, in order to solve at least one of the technical problems described in the background art.

[0006] Specifically, in a first aspect, this application provides a meloxicam-containing tablet comprising, by weight, the following components:

[0007] Component A consists of 11-34 parts.

[0008] 30-60 parts starch

[0009] 20-40 parts dextrin

[0010] Lubricant 0.02-0.2 parts.

[0011] Component A comprises 1-4 parts meloxicam and 10-30 parts glucose, wherein the particle size of meloxicam is 20-30 μm and the particle size of glucose is 50-100 μm.

[0012] By using the above technical solution, by preparing meloxicam and glucose as component A and mixing it with other excipients such as starch and dextrin, the solubility of meloxicam tablets can be significantly improved and its bioavailability can be increased.

[0013] Preferably, the lubricant is selected from one or a combination of talc, micronized silica gel, and magnesium stearate.

[0014] Preferably, the weight ratio of meloxicam to glucose is 1:5 to 1:10.

[0015] Preferably, the meloxicam-containing tablet further comprises:

[0016] Component B, wherein component B comprises 1-2 parts sodium alginate and 1-2 parts mannitol.

[0017] Preferably, the weight ratio of sodium alginate to mannitol is 1:0.5-1:1.

[0018] Preferably, the hardness of the meloxicam-containing tablets is 6-9 kg / cm². 2 .

[0019] A second aspect of this application provides a method for preparing meloxicam-containing tablets as described in the first aspect of this application, comprising the steps of:

[0020] To prepare starch slurry, take 10-30 parts by weight of purified water and heat it to 90-95℃. Add 2-3 parts by weight of starch while stirring to make starch slurry.

[0021] Granulation: Component A, starch and dextrin as described in the first aspect of this application are added to a wet granulator, followed by starch slurry. The granulator is operated at a speed of 3000-5000 r / min for 6-10 min and then fed into a fluidized bed. The granulator is dried at 75-90℃ for 40-80 min.

[0022] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0023] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0024] Preferably, the starch paste is made of amylose with a molecular weight of 500-800 Da.

[0025] Preferably, in the granulation step, the wet granulator operates at a speed of 4000 r / min for 8 minutes.

[0026] Preferably, in the granulation step, the drying temperature of the fluidized bed is 80°C for 60 minutes.

[0027] Preferably, the preparation method of component A includes the following steps:

[0028] The first step is mixing. Weigh out the required amount of meloxicam and mix it evenly with twice the amount of glucose as meloxicam to obtain the first mixture.

[0029] The second step involves mixing the initial mixture with the remaining glucose by weight to obtain component A.

[0030] A third aspect of this application provides a method for preparing meloxicam-containing tablets as described in the first aspect of this application, comprising the steps of:

[0031] To prepare starch slurry, take 10-30 parts by weight of purified water and heat it to 90-95℃. Add 2-3 parts by weight of starch while stirring to make starch slurry.

[0032] Granulation: Component A, starch, dextrin and component B as described in the first aspect of this application are added to a wet granulator, followed by starch slurry. The granulator is operated at a speed of 3000-5000 r / min for 6-10 min and then fed into a fluidized bed. The granulator is dried at 75-90℃ for 40-80 min.

[0033] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0034] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0035] Preferably, the starch is amylose with a molecular weight of 500-800 Da.

[0036] Preferably, in the granulation step, the wet granulator operates at a speed of 4000 r / min for 8 minutes.

[0037] Preferably, in the granulation step, the drying temperature of the fluidized bed is 80°C for 60 minutes.

[0038] Preferably, the preparation method of component B includes the following steps:

[0039] Dissolve mannitol completely in 10 parts by weight of pure water to obtain a mannitol solution;

[0040] Heat the mannitol solution to 80°C and add sodium alginate while stirring.

[0041] In summary, this application has the following beneficial effects:

[0042] 1. The meloxicam-containing tablets provided in this application, by preparing meloxicam and glucose as component A, and mixing it with other excipients such as starch and dextrin, can significantly improve the solubility of meloxicam tablets and improve their bioavailability;

[0043] 2. The meloxicam-containing tablets provided in this application, by adding component B containing sodium alginate and mannitol, can effectively reduce the effect of meloxicam on pets' appetite and reduce the adverse reactions of meloxicam tablets;

[0044] 3. The method for preparing meloxicam tablets provided in this application, by mixing the components and adding starch slurry, can make the prepared meloxicam tablets have better stability and solubility. Implementation

[0045] Exemplary embodiments will now be described in detail. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with this application. Rather, they are merely examples of apparatuses and methods consistent with some aspects of this application as detailed in the appended claims.

[0046] The terminology used in this application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The singular forms “a,” “the,” and “the” used in this application and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term “and / or” as used herein refers to and includes any or all possible combinations of one or more of the associated listed items.

[0047] The present application will be described in detail below through examples.

[0048] Existing meloxicam tablets often suffer from low bioavailability and reduced therapeutic efficacy due to the poor water solubility of meloxicam. Therefore, this invention aims to provide a meloxicam-containing tablet and its preparation method that solves the aforementioned technical problems. The meloxicam-containing tablet, by weight, comprises: component A (11-34 parts), starch (30-60 parts), dextrin (20-40 parts), and lubricant (0.02-0.2 parts). Component A includes 1-4 parts meloxicam and 10-30 parts glucose, with the meloxicam having a particle size of 20-30 μm and the glucose having a particle size of 50-100 μm. According to this invention, by preparing meloxicam and glucose as component A and mixing it with other excipients such as starch and dextrin, the solubility and bioavailability of the meloxicam tablet can be significantly improved.

[0049] Before introducing the technical solution of this application, the main components involved in this application will be described first. It should be noted that compounds not specifically emphasized in this application can all be purchased commercially, and are not limited to the types described below.

[0050] Sodium alginate: a white or pale yellow powder, almost odorless and tasteless. Sodium alginate is soluble in water but insoluble in organic solvents such as ethanol, ether, and chloroform. It dissolves in water to form a viscous liquid; a 1% aqueous solution has a pH of 6-8. Its viscosity is stable at pH 6-9, and decreases when heated above 80℃. Sodium alginate is non-toxic, with an LD50 > 5000 mg / kg.

[0051] Mannitol: Chemical formula C6H14O6, molecular weight 182.172. White crystalline powder, readily soluble in water, practically insoluble in ethanol and ether. Melting point 166~170°C.

[0052] To better understand the above technical solution, the following will provide a detailed explanation of the technical solution in conjunction with specific implementation methods.

[0053] Experiment Example 1: Solubility Experiment of Meloxicam Tablets

[0054] This embodiment describes the experimental method for the solubility test of the Sino-US loxicam tablets in this application. Unless otherwise specified, the solubility test of the Sino-US loxicam tablets in this application shall be carried out according to the method of this experimental example.

[0055] The specific determination method is as follows: Following the dissolution and release determination method (Chinese Pharmacopoeia 2015 Edition, General Chapter 0931, Method II, Paddle Method), take 900 ml of pH 1.0 hydrochloric acid solution medium, rotate at 75 r / min, and operate according to the method. After 30 min, collect the solution, filter it, and use the resulting filtrate as the test solution. Separately, accurately weigh 20 mg of meloxicam reference standard, place it in a 100 ml volumetric flask, add 10 ml of 0.1 mol / L sodium hydroxide solution, sonicate to dissolve, then dilute to the mark with dissolution medium, shake well, accurately measure 2 mL, place it in a 50 mL volumetric flask, dilute to the mark with dissolution medium, shake well, and use this as the reference solution. Measure the absorbance at a wavelength of 362 nm using ultraviolet-visible spectrophotometry (Chinese Pharmacopoeia 2015 Edition, General Chapter 0401), and calculate the dissolution rate.

[0056] Experiment Example 2: Food Intake Experiment

[0057] This embodiment describes the experimental method for the food intake experiment in this application. Unless otherwise specified, the food intake experiments in this application shall be carried out in accordance with the method of this experimental example.

[0058] Adult beagle dogs with a weight range of 10.50±1kg were selected and administered approximately 7.5mg of meloxicam per 10kg of body weight. The administration was once daily. After administration, the dogs were given 10ml of pure water orally. Food was not introduced until 4 hours after administration.

[0059] Experimental Example 3: Determination of Meloxicam Content

[0060] The determination was performed according to high performance liquid chromatography (Appendix 0512 of the Chinese Veterinary Pharmacopoeia). Chromatographic conditions and system suitability tests were conducted using octadecylsilane-bonded silica gel as the stationary phase; methanol-0.1 mol / L ammonium acetate solution (1:1) as the mobile phase; detection wavelength was 362 nm; and column temperature was 40 °C. The theoretical plate number, calculated based on the guanosine monophosphate peak, was not less than 2000.

[0061] Accurately weigh 20 tablets of this product, grind them into a fine powder, and accurately weigh an appropriate amount (approximately equivalent to 2 mg of meloxicam). Place the powder in a 100 ml volumetric flask, add 70 ml of alkaline methanol solution, sonicate for 15 minutes to dissolve the meloxicam, cool, dilute to the mark with alkaline methanol solution, shake well, filter, accurately measure 5 ml of the filtrate, place it in a 10 ml volumetric flask, quantitatively dilute to the mark with alkaline methanol solution, shake well, and use this as the test solution. Accurately inject 20 μl into the liquid chromatograph and record the chromatogram. Separately, accurately weigh an appropriate amount of meloxicam reference standard, dissolve and dilute it with alkaline methanol solution to prepare a solution containing approximately 10 μg per ml, and determine it using the same method. Calculate the result by peak area using the external standard method.

[0062] Experiment Example 4

[0063] This experimental example examines the effect of different implementation methods on the solubility of meloxicam active pharmaceutical ingredient.

[0064] Option A

[0065] Weigh the components according to the following parts by weight:

[0066] Two parts of meloxicam, with a particle size of 40-60 μm; 20 parts of glucose, with a particle size of 20-30 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0067] Prepare tablets containing meloxicam using the following steps:

[0068] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to prepare starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0069] Granulation: The above meloxicam, glucose, starch and dextrin are added to a wet granulator, followed by starch slurry. The granulation process is carried out at 4000 r / min for 8 min, and then the granulation is carried out in a fluidized bed at 80℃ for 60 min.

[0070] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0071] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0072] Option B

[0073] Similar to Option A, the difference lies in the different components:

[0074] Weigh the components according to the following parts by weight:

[0075] Two parts of meloxicam, with a particle size of 40-60 μm; 20 parts of glucose, with a particle size of 120-150 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0076] Option C

[0077] Similar to Option A, the difference lies in the different components:

[0078] Weigh the components according to the following parts by weight:

[0079] 2 parts meloxicam, with a particle size of 20-30 μm; 20 parts glucose, with a particle size of 20-30 μm; 50 parts starch; 30 parts dextrin; and 0.1 parts magnesium stearate.

[0080] Option D

[0081] Similar to Option A, the difference lies in the different components:

[0082] Weigh the components according to the following parts by weight:

[0083] Two parts of meloxicam, with a particle size of 20-30 μm; 20 parts of glucose, with a particle size of 120-150 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0084] Option E

[0085] Similar to Option A, the difference lies in the different components:

[0086] Weigh the components according to the following parts by weight:

[0087] Two parts of meloxicam, with a particle size of 40-60 μm; 20 parts of glucose, with a particle size of 50-100 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0088] Option F

[0089] Similar to Option A, the difference lies in the different components:

[0090] Weigh the components according to the following parts by weight:

[0091] Two parts of meloxicam, with a particle size of 20-30 μm; 20 parts of glucose, with a particle size of 50-100 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0092] Option G

[0093] Similar to Option A, the difference lies in the different components:

[0094] Weigh the components according to the following parts by weight:

[0095] Two parts of meloxicam, with a particle size of 20-30 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0096] Prepare tablets containing meloxicam using the following steps:

[0097] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to prepare starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0098] Granulation: The above meloxicam, starch and dextrin are added to a wet granulator, followed by starch slurry. The granulation process is carried out at 4000 r / min for 8 min, and then the granulation is carried out in a fluidized bed at 80℃ for 60 min.

[0099] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0100] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0101] Option H

[0102] Similar to scheme F, the difference lies in the preparation method:

[0103] Prepare tablets containing meloxicam using the following steps:

[0104] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0105] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to prepare starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0106] Granulation: Add the above components A, starch and dextrin into a wet granulator, then add starch slurry, operate at 4000 r / min for 8 min, and then enter a fluidized bed to dry at 80℃ for 60 min.

[0107] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0108] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0109] Option I

[0110] Similar to scheme A, the difference lies in the preparation method:

[0111] Prepare tablets containing meloxicam using the following steps:

[0112] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0113] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to prepare starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0114] Granulation: Add the above components A, starch and dextrin into a wet granulator, then add starch slurry, operate at 4000 r / min for 8 min, and then enter a fluidized bed to dry at 80℃ for 60 min.

[0115] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0116] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0117] The meloxicam-containing tablets prepared according to Scheme A-Scheme I were tested for dissolution of meloxicam according to the method in Experimental Example 1. The experimental results are shown in the table below.

[0118] Table 1. Dissolution rates of the saline-amycin component in Schemes A-I

[0119] Group Dissolution rate (%) at 30 min Option A 43 Option B 45 Option C 55 Option D 52 Option E 43 Option F 60 Option G 42 Option H 71 Option I 56 .

[0120] According to Table 1, firstly, for scheme F, the dissolution rate of meloxicam is significantly improved compared to scheme AE. This indicates that, without changes in other components, the particle size relationship between meloxicam and glucose in component A affects the dissolution rate of meloxicam.

[0121] Second, comparing scheme F and scheme G, scheme G does not contain glucose. Although its meloxicam particle size is the same as that of scheme F, its dissolution rate is still significantly lower than that of scheme F, indicating that glucose in scheme F is also an indispensable component for the dissolution of meloxicam.

[0122] Third, comparing schemes H and F, with the same components, the solubility of meloxicam in scheme H is significantly higher than that in scheme F, indicating that the preparation process of component A in scheme H affects the dissolution of meloxicam.

[0123] Fourth, for Scheme I, the components are the same as those in Scheme A. However, although it adopts a component A preparation scheme similar to that in Scheme F, the dissolution rate of meloxicam has not been significantly improved, indicating that the preparation scheme of component A is more suitable for the combination of meloxicam and glucose with a specific particle size.

[0124] Experimental Example 5

[0125] This experiment investigated the effect of administering meloxicam-containing tablets in different formulations on the food intake of broiler dogs.

[0126] Scheme J

[0127] Weigh the components according to the following parts by weight:

[0128] Two parts of meloxicam, with a particle size of 20-30 μm; 20 parts of glucose, with a particle size of 50-100 μm; 50 parts of starch; 30 parts of dextrin; 0.1 parts of magnesium stearate; and 1 part of sodium alginate.

[0129] Prepare tablets containing meloxicam using the following steps:

[0130] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0131] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to prepare starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0132] Granulation: Add the above components A, starch, dextrin and sodium alginate into a wet granulator, then add starch slurry, operate at 4000 r / min for 8 min, enter the fluidized bed, and dry at 80℃ for 60 min.

[0133] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0134] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0135] Option K

[0136] Weigh the components according to the following parts by weight:

[0137] 2 parts meloxicam, with a particle size of 20-30 μm; 20 parts glucose, with a particle size of 50-100 μm; 50 parts starch; 30 parts dextrin; 0.1 parts magnesium stearate; 1 part mannitol.

[0138] Prepare tablets containing meloxicam using the following steps:

[0139] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0140] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to prepare starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0141] Granulation: Add the above components A, starch, dextrin and mannitol into a wet granulator, then add starch slurry, operate at 4000 r / min for 8 min, and then enter a fluidized bed to dry at 80℃ for 60 min.

[0142] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0143] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0144] Option L

[0145] Weigh the components according to the following parts by weight:

[0146] Two parts of meloxicam, with a particle size of 20-30 μm; 20 parts of glucose, with a particle size of 50-100 μm; 50 parts of starch; 30 parts of dextrin; 0.1 parts of magnesium stearate; 1 part of sodium alginate; and 1 part of mannitol.

[0147] Prepare tablets containing meloxicam using the following steps:

[0148] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0149] To prepare component B, mannitol was fully dissolved in 10 parts by weight of pure water to obtain a mannitol solution; the mannitol solution was heated to 80°C, and sodium alginate was added while stirring.

[0150] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to prepare starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0151] Granulation: Add the above components A, starch, dextrin and component B to a wet granulator, then add starch slurry, operate at 4000 r / min for 8 min, enter the fluidized bed, and dry at 80℃ for 60 min.

[0152] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0153] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0154] Option M

[0155] Weigh the components according to the following parts by weight:

[0156] Two parts of meloxicam, with a particle size of 20-30 μm; 20 parts of glucose, with a particle size of 50-100 μm; 50 parts of starch; 30 parts of dextrin; 0.1 parts of magnesium stearate; 1 part of sodium alginate; and 1 part of mannitol.

[0157] Prepare tablets containing meloxicam using the following steps:

[0158] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0159] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to prepare starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0160] Granulation: Add the above components A, starch, dextrin, mannitol and sodium alginate into a wet granulator, then add starch slurry, operate at 4000 r / min for 8 min, enter the fluidized bed, and dry at 80℃ for 60 min.

[0161] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0162] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

[0163] The meloxicam-containing tablets prepared according to schemes A, F, H, J-M were used to determine the daily food intake of beagle dogs according to the method in Experimental Example 2. The experimental results are shown in the table below.

[0164] Table 2. Food intake of experimental dogs after administration of meloxicam tablets in regimens A, F, H, J-M

[0165] Group Average food intake (g) in the 7 days prior to the experiment Average daily food intake (g) during the experiment Average daily food intake (g) in the first 3 days after the experiment Average daily food intake (g) 4-7 days after the experiment Option A 177 108 133 179 Option F 186 102 130 185 Option H 192 98 127 180 Scheme J 188 106 130 182 Option K 180 100 139 178 Option L 169 122 155 171 Option M 171 109 144 170 .

[0166] As shown in Table 2, after adopting scheme L, the experimental dogs exhibited better food intake both during the experiment and for the first three days afterward. This indicates that the meloxicam tablets prepared according to scheme L caused milder adverse reactions of anorexia in the test animals, thus reducing the likelihood of other derivative diseases. Comparing scheme L and scheme M, scheme L showed better anti-anorexia effects than scheme M, indicating that the preparation method of component B provided in this application has a positive impact on the adverse reactions of anorexia in experimental dogs. Example 1

[0167] Weigh the components according to the following parts by weight:

[0168] 1 part meloxicam, with a particle size of 20-30 μm; 10 parts glucose, with a particle size of 50-100 μm; 30 parts starch; 20 parts dextrin; and 0.02 parts magnesium stearate.

[0169] Prepare tablets containing meloxicam using the following steps:

[0170] To prepare starch slurry, take 10 parts of purified water and heat it to 90°C. Add 2 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0171] Granulation: The above meloxicam, glucose, starch and dextrin are added to a wet granulator, followed by starch slurry. The mixture is operated at 3000 r / min for 6 min and then fed into a fluidized bed. It is dried at 75℃ for 40 min.

[0172] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0173] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Example 2

[0174] Weigh the components according to the following parts by weight:

[0175] Two parts of meloxicam, with a particle size of 20-30 μm; 20 parts of glucose, with a particle size of 50-100 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0176] Prepare tablets containing meloxicam using the following steps:

[0177] To prepare starch slurry, take 15 parts of purified water and heat it to 92°C. Add 2.5 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0178] Granulation: The above meloxicam, glucose, starch and dextrin are added to a wet granulator, followed by starch slurry. The granulation process is carried out at 4000 r / min for 8 min, and then the granulation is carried out in a fluidized bed at 80℃ for 60 min.

[0179] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0180] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Example 3

[0181] Weigh the components according to the following parts by weight:

[0182] The mixture contains 4 parts meloxicam with a particle size of 20-30 μm; 30 parts glucose with a particle size of 50-100 μm; 60 parts starch; 40 parts dextrin; and 0.2 parts magnesium stearate.

[0183] Prepare tablets containing meloxicam using the following steps:

[0184] To prepare starch slurry, take 20 parts of purified water and heat it to 95°C. Add 3 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0185] Granulation: The above meloxicam, glucose, starch and dextrin are added to a wet granulator, followed by starch slurry. The granulation process is carried out at 5000 r / min for 10 min, and then the granulation process is carried out in a fluidized bed and dried at 90℃ for 80 min.

[0186] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0187] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Example 4

[0188] Weigh the components according to the following parts by weight:

[0189] 1 part meloxicam, with a particle size of 20-30 μm; 10 parts glucose, with a particle size of 50-100 μm; 30 parts starch; 20 parts dextrin; and 0.02 parts magnesium stearate.

[0190] Prepare tablets containing meloxicam using the following steps:

[0191] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0192] To prepare starch slurry, take 10 parts of purified water and heat it to 90°C. Add 2 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0193] Granulation: Add the above components A, starch and dextrin into a wet granulator, then add starch slurry, operate at 3000 r / min for 6 min, and then enter a fluidized bed to dry at 75℃ for 40 min.

[0194] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0195] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Example 5

[0196] Weigh the components according to the following parts by weight:

[0197] Two parts of meloxicam, with a particle size of 20-30 μm; 20 parts of glucose, with a particle size of 50-100 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0198] Prepare tablets containing meloxicam using the following steps:

[0199] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0200] To prepare starch slurry, take 15 parts of purified water and heat it to 92°C. Add 2.5 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0201] Granulation: Add the above components A, starch and dextrin into a wet granulator, then add starch slurry, operate at 4000 r / min for 8 min, and then enter a fluidized bed to dry at 80℃ for 60 min.

[0202] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0203] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Example 6

[0204] Weigh the components according to the following parts by weight:

[0205] The mixture contains 4 parts meloxicam with a particle size of 20-30 μm; 30 parts glucose with a particle size of 50-100 μm; 60 parts starch; 40 parts dextrin; and 0.2 parts magnesium stearate.

[0206] Prepare tablets containing meloxicam using the following steps:

[0207] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0208] To prepare starch slurry, take 20 parts of purified water and heat it to 95°C. Add 3 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0209] Granulation: Add the above components A, starch and dextrin into a wet granulator, then add starch slurry, operate at 5000 r / min for 10 min, enter the fluidized bed, and dry at 90℃ for 80 min;

[0210] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0211] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Example 7

[0212] Weigh the components according to the following parts by weight:

[0213] 1 part meloxicam, with a particle size of 20-30 μm; 10 parts glucose, with a particle size of 50-100 μm; 30 parts starch; 20 parts dextrin; 0.02 parts magnesium stearate; 1 part sodium alginate; 1 part mannitol.

[0214] Prepare tablets containing meloxicam using the following steps:

[0215] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0216] To prepare component B, mannitol was fully dissolved in 10 parts by weight of pure water to obtain a mannitol solution; the mannitol solution was heated to 80°C, and sodium alginate was added while stirring.

[0217] To prepare starch slurry, take 10 parts of purified water and heat it to 90°C. Add 2 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0218] Granulation: Add the above components A, starch, dextrin and component B to a wet granulator, then add starch slurry, operate at 3000 r / min for 6 min, enter the fluidized bed, and dry at 75℃ for 40 min.

[0219] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0220] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Example 8

[0221] Weigh the components according to the following parts by weight:

[0222] 2 parts meloxicam, with a particle size of 20-30 μm; 20 parts glucose, with a particle size of 50-100 μm; 50 parts starch; 30 parts dextrin; 0.1 parts magnesium stearate; 1.5 parts sodium alginate; and 1.5 parts mannitol.

[0223] Prepare tablets containing meloxicam using the following steps:

[0224] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0225] To prepare component B, mannitol was fully dissolved in 10 parts by weight of pure water to obtain a mannitol solution; the mannitol solution was heated to 80°C, and sodium alginate was added while stirring.

[0226] To prepare starch slurry, take 20 parts of purified water and heat it to 92°C. Add 2.5 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0227] Granulation: Add the above components A, starch, dextrin and component B to a wet granulator, then add starch slurry, operate at 4000 r / min for 8 min, enter the fluidized bed, and dry at 80℃ for 50 min.

[0228] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0229] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Example 9

[0230] Weigh the components according to the following parts by weight:

[0231] Meloxicam 4 parts, with a particle size of 20-30 μm; glucose 30 parts, with a particle size of 50-100 μm; starch 60 parts; dextrin 40 parts; magnesium stearate 0.2 parts; sodium alginate 2 parts; mannitol 2 parts.

[0232] Prepare tablets containing meloxicam using the following steps:

[0233] Preparation of component A: Step 1: Weigh out meloxicam according to the required weight parts and mix it evenly with 2 times the weight parts of glucose to obtain the first mixture; Step 2: Mix the first mixture evenly with the remaining weight parts of glucose to obtain component A;

[0234] To prepare component B, mannitol was fully dissolved in 10 parts by weight of pure water to obtain a mannitol solution; the mannitol solution was heated to 80°C, and sodium alginate was added while stirring.

[0235] To prepare starch slurry, take 30 parts of purified water and heat it to 95°C. Add 3 parts of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da.

[0236] Granulation: Add the above components A, starch, dextrin and component B to a wet granulator, then add starch slurry, operate at 5000 r / min for 10 min, then enter a fluidized bed and dry at 90℃ for 80 min.

[0237] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0238] For tableting, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets, controlling the tablet weight to 2 mg. Comparative Example 1

[0239] Weigh the components according to the following parts by weight:

[0240] Two parts of meloxicam, with a particle size of 20-30 μm; 50 parts of starch; 30 parts of dextrin; and 0.1 parts of magnesium stearate.

[0241] Prepare tablets containing meloxicam using the following steps:

[0242] To prepare starch slurry, take 20 parts by weight of purified water and heat it to 90°C. Add 2 parts by weight of starch while stirring to make starch slurry.

[0243] Granulation: The above meloxicam, starch and dextrin are added to a wet granulator, followed by starch slurry. The granulation process is carried out at 4000 r / min for 8 min, and then the granulation is carried out in a fluidized bed at 80℃ for 60 min.

[0244] Sieve the particles obtained in the previous step through a 40-mesh sieve.

[0245] To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets. Comparative Example 2

[0246] Meloxicam tablets are sold in a certain city. Comparative Example 3

[0247] The preparation method is basically the same as that in Example 4, except that:

[0248] The starch paste is made from linear starch with a molecular weight of 1000-2000 Da.

[0249] Detection Example 1

[0250] Meloxicam tablets prepared according to the methods of Examples 1-9 and Comparative Examples 1-3 were tested for dissolution and content (yield) according to the methods in Experimental Examples 1 and 3. It is understood that the same batch of product was used for experiments in the same group. The experimental results are shown in Table 3.

[0251] Table 3. Results of meloxicam dissolution and yield tests in Examples 1-9 and Comparative Examples 1-3

[0252] Group Dissolution rate at 30 min (%) Yield (%) Example 1 58.9 99.5 Example 2 60.1 99.6 Example 3 60.4 99.3 Example 4 72.3 100.4 Example 5 69.5 99.9 Example 6 70.8 100.5 Example 7 71.5 99.0 Example 8 70.8 99.3 Example 9 70.4 100.1 Comparative Example 1 43.6 99.6 Comparative Example 2 50.2 99.4 Comparative Example 3 66.0 99.2 .

[0253] According to Table 3, firstly, the meloxicam tablets prepared in the embodiments of this application all have a content of 99%-101%, which meets the requirements of product quality standards; secondly, the meloxicam tablets obtained by the preparation method of the embodiments of this application have a significantly higher dissolution rate than commercially available products, which is more conducive to the absorption of meloxicam in the body.

[0254] Comparing Examples 4-6 with Examples 1-3, with essentially the same components, the dissolution rate of Examples 4-6 is significantly higher than that of Examples 1-3, indicating that the preparation method of component A proposed in this application has a beneficial effect on the dissolution of meloxicam.

[0255] Compared with Comparative Example 5 and Comparative Example 3, when higher molecular weight amylose is used in the starch slurry during the preparation process, it will affect the dissolution of the final product.

[0256] Further experiments by the applicant revealed that the hardness of the meloxicam-containing tablets prepared in this application was 6-9 kg / cm². 2When outside the specified range, the dissolution rate of the product, meloxicam, showed a decreasing trend at 30 minutes. Therefore, product hardness should also be considered as one of the quality control indicators in this application.

[0257] In summary, the meloxicam-containing tablets and their preparation method provided in this application can achieve the following technical effects on the basis of obtaining qualified products: (1) improving the dissolution rate of meloxicam; and (2) reducing the intensity of adverse reactions to meloxicam. Therefore, the meloxicam-containing tablets and their preparation method provided in this application have good technical effects and promising prospects for industrial application.

[0258] It should be noted that talc, micronized silica gel, and magnesium stearate have similar properties and can be substituted for each other without affecting the conclusion of this application.

[0259] For those skilled in the art, the technical features in the above embodiments can be freely combined, and the resulting technical solutions also belong to the embodiments disclosed in this application.

[0260] Furthermore, without departing from the principles of this application, several improvements and modifications may be made to this application, and these improvements and modifications also fall within the protection scope of the claims of this application.

Claims

1. A tablet containing meloxicam, characterized in that, By weight, including components: Component A consists of 11-34 parts. Component B, 30-60 parts starch 20-40 parts dextrin Lubricant 0.02-0.2 parts, Component A comprises 1-4 parts meloxicam and 10-30 parts glucose, wherein the particle size of meloxicam is 20-30 μm and the particle size of glucose is 50-100 μm; Component B comprises 1-2 parts sodium alginate and 1-2 parts mannitol. The preparation method of component A includes the following steps: First step mixing: weigh meloxicam according to the required weight parts, and mix it evenly with 2 times the weight parts of glucose to obtain a first mixture; Second step mixing: mix the first mixture evenly with the remaining weight parts of glucose to obtain component A. The preparation method of component B includes the following steps: dissolving mannitol fully in 10 parts by weight of pure water to obtain a mannitol solution; heating the mannitol solution to 80°C and adding sodium alginate while stirring.

2. The meloxicam-containing tablet according to claim 1, characterized in that: The weight ratio of meloxicam to glucose is 1:5 to 1:

10.

3. The meloxicam-containing tablet according to claim 1, characterized in that: The weight ratio of sodium alginate to mannitol is 1:0.5-1:

1.

4. The meloxicam-containing tablet according to claim 1, characterized in that: The tablets containing meloxicam have a hardness of 6-9 kg / cm². 2 .

5. A method for preparing meloxicam-containing tablets as described in any one of claims 1-4, characterized in that, Including the following steps: To prepare starch slurry, take 10-30 parts by weight of purified water and heat it to 90-95℃. Add 2-3 parts by weight of starch while stirring to make starch slurry. The starch slurry is made of amylose with a molecular weight of 500-800 Da. Granulation: Component A, starch, dextrin and component B as described in any one of claims 1-4 are added to a wet granulator, followed by starch slurry. The granulator is operated at a speed of 3000-5000 r / min for 6-10 min and then fed into a fluidized bed. The granulator is dried at 75-90℃ for 40-80 min. Sieve the particles obtained in the previous step through a 40-mesh sieve. To compress the tablets, add the granules obtained in the previous step to magnesium stearate, mix, and compress into tablets.

6. The method for preparing meloxicam-containing tablets according to claim 5, characterized in that: In the granulation step, the wet granulator operates at a speed of 4000 r / min for 8 minutes.