Ondansetron hydrochloride tablet and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses an ondansetron hydrochloride tablet and a preparation method thereof.The preparation method comprises the steps that 1, ondansetron hydrochloride and part of first filler are jointly sieved, and a first premix is obtained; (2) sieving the rest first filling agent and the first premix to obtain a second premix; (3) co-sieving the second filler and the second premix to obtain a third premix; (4) mixing the third premix in a mixer; and (5) adding a lubricant, and carrying out total mixing, tabletting and coating. According to the invention, the ondansetron hydrochloride tablet is prepared by a powder direct compression process, mixing uniformity is guaranteed by adopting a manner of premixing through multiple times of co-sieving, and anhydrous lactose is adopted as a filler to reduce the moisture of the product and guarantee the stability of the product; the microcrystalline cellulose and the pregelatinized starch are used as filling agents to ensure that the fluidity and compressibility of total mixed powder are good, and the ondansetron hydrochloride tablet with the dissolution curve similar to that of a reference preparation and stable quality is prepared.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and particularly relates to a stable ondansetron hydrochloride tablet and a preparation method thereof. Background Art

[0002] Ondansetron Hydrochloride, chemically named 2,3-dihydro-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-4(1H)-carbazolone hydrochloride, is a selective 5-hydroxytryptamine 3 (5-HT 3 ), receptor antagonist, which exerts an antiemetic effect by blocking 5-HT 3 receptors. At antiemetic doses, it can also enhance gastric emptying, helping to relieve nausea, and is mainly used for preventing and treating nausea and vomiting caused by chemotherapy, radiotherapy or surgery.

[0003] The ondansetron hydrochloride tablet was first developed by GlaxoSmithKline (GSK) in 1990. The ondansetron hydrochloride tablet contains ondansetron hydrochloride calculated as ondansetron (C 18 H 19 N 3 O) of 8 mg and 4 mg, and the proportion of the active ingredient is low, which is a low drug-loading tablet. The mixing uniformity is a problem to be solved in the preparation process of the ondansetron hydrochloride tablet.

[0004] Patent Application No. US19860877805A discloses the direct powder compression process and the wet granulation process for ondansetron hydrochloride tablets. In the direct powder compression process, the ondansetron hydrochloride raw material is first passed through a 60-mesh sieve, and then directly compressed into tablets after being mixed with calcium hydrogen phosphate, croscarmellose sodium, and magnesium stearate. Among them, the proportion of calcium hydrogen phosphate in the formulation is very high, reaching 74.3% - 92.3%. Calcium hydrogen phosphate has a relatively high hardness, and excessive use may lead to the following results: (1) It affects the compressibility of the tablets, resulting in overly hard tablets, which affects disintegration and dissolution. The friability of the tablets increases and they are prone to breakage; (2) Excessive use of calcium hydrogen phosphate may lead to a decrease in the fluidity of the material, especially in the direct compression process, where uneven filling is likely to occur during tableting, resulting in an increase in tablet weight variation; (3) The porosity of calcium hydrogen phosphate decreases, and excessive use may cause the raw material drug to be encapsulated in a dense excipient matrix, making it difficult to contact the dissolution medium, thereby resulting in incomplete dissolution of the raw material drug; (4) Excessive use of calcium hydrogen phosphate may accelerate the wear of tableting equipment, increase costs, affect the smoothness of the production process, and is not conducive to large-scale commercial production. At the same time, in the direct powder compression process, since the raw and auxiliary materials are not granulated and the powder is relatively fine, sticking to the punch is likely to occur during tableting. In the wet granulation process, the ondansetron hydrochloride raw material is first sieved, mixed with lactose, starch, and pregelatinized starch, and water is added as a binder for wet granulation. After drying, dry screening is carried out, and then the lubricant magnesium stearate is added for total mixing and then tableting. Compared with the direct powder compression process, the wet granulation process is more complex and energy-consuming, resulting in high costs for large-scale commercial production. Therefore, it is necessary to develop a preparation process for ondansetron hydrochloride tablets that is simple, has good mixing uniformity, and stable quality. Summary of the Invention

[0005] Object of the Invention: The technical problem to be solved by the present invention is to provide an ondansetron hydrochloride tablet and its preparation method in view of the deficiencies of the prior art.

[0006] To solve the above technical problems, the present invention discloses the following technical solutions: In a first aspect, the present invention discloses an ondansetron hydrochloride composition.

[0007] In some embodiments, the composition comprises the following components in parts by weight: Ondansetron hydrochloride 8 - 12 parts First filler 158 - 228 parts Second filler 68 - 142 parts Lubricant 0.1 - 7 parts Coating powder 5 - 15 parts The first filler is anhydrous lactose, the second filler is microcrystalline cellulose and pregelatinized starch, and the content of microcrystalline cellulose in the second filler is 55 - 95% wt, preferably 60 - 90% wt, such as 62%, 67%, 72%, 76%, 80%, 85%, 88%.

[0008] In some embodiments, the composition comprises the following components in parts by weight: Ondansetron hydrochloride 9.98 parts The first filler 160 - 226 parts The second filler 72 - 140 parts Lubricant 0.3 - 5 parts Coating powder 5 - 15 parts In some embodiments, the composition comprises the following components in parts by weight: Ondansetron hydrochloride 9.98 parts The first filler 162 - 224 parts The second filler 76 - 138 parts Lubricant 0.5 - 3 parts Coating powder 8 - 12 parts In some embodiments, the lubricant is selected from magnesium stearate, calcium stearate, zinc stearate, sodium fumarate stearate or a combination of any of the foregoing.

[0009] In some embodiments, the particle size D of the ondansetron hydrochloride 90 is 30 - 150 μm; the particle size D of the microcrystalline cellulose in the second filler 50 is 70 - 130 μm; the pregelatinized starch in the second filler with a particle size below 150 μm accounts for more than 90% of its total mass, and the pregelatinized starch with a particle size above 425 μm accounts for less than 0.5% of its total mass.

[0010] In a second aspect, the present invention discloses an ondansetron hydrochloride tablet.

[0011] In some embodiments, the method for preparing the ondansetron hydrochloride tablets from the composition is the direct powder compression method.

[0012] In some embodiments, the method for preparing the ondansetron hydrochloride tablets from the composition comprises the following steps: (1) Ondansetron hydrochloride and a part of the first filler are sieved together to obtain a first premix; (2) The remaining first filler and the first premix are sieved together to obtain a second premix; (3) The second filler and the second premix are sieved together to obtain a third premix; (4) The third premix is mixed in a mixer; (5) A lubricant is added for total mixing, tableting, and coating.

[0013] In some embodiments, the particle size D of ondansetron hydrochloride 90 is 30 - 150 μm; the particle size D of microcrystalline cellulose in the second filler 50 is 70 - 130 μm; the pregelatinized starch with a particle size of less than 150 μm in the second filler accounts for more than 90% of its total mass, and the pregelatinized starch with a particle size of more than 425 μm accounts for less than 0.5% of its total mass.

[0014] In step (1), the partial first filler is 40% - 60% of the total mass of the first filler, such as 50%. In a rotary granulator, the ondansetron hydrochloride raw material and the partial first filler are sieved together; the rotation speed of the rotary granulator is 800 - 1200 rpm, such as 1000 rpm, and the particle size of the sieve mesh in the rotary granulator is 0.6 - 1.4 mm, such as 1.0 mm.

[0015] In step (2), in a rotary granulator, the remaining first filler and the first premix are sieved together; the rotation speed of the rotary granulator is 600 - 1000 rpm, such as 800 rpm, and the particle size of the sieve mesh in the rotary granulator is 0.6 - 1.4 mm, such as 1.0 mm.

[0016] In step (3), in a rotary granulator, the second filler and the second premix are sieved together; the rotation speed of the rotary granulator is 600 - 1000 rpm, such as 800 rpm, and the particle size of the sieve mesh in the rotary granulator is 0.6 - 1.4 mm, such as 1.0 mm.

[0017] In step (4), in a mixer, the obtained premix is mixed; the rotation speed of the mixing is 10 - 20 rpm, such as 15 rpm, and the time is 2 - 7 min, such as 5 min; the loading coefficient of the mixer is 45% - 70%.

[0018] In step (5), in a mixer, a lubricant is added and mixed; the rotation speed of the mixing is 10 - 20 rpm, such as 11 rpm, and the time is 1 - 5 min, such as 2 min; the loading coefficient of the mixer is 45% - 70%.

[0019] In step (5), during the tabletting process, the environmental humidity is controlled below 65%, such as 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, etc.; during the tabletting process, the tablet weight variation is controlled within ±5%, and the hardness is 9.0 - 11.0 kg.

[0020] In step (5), the coating powder is the film coating premix YS - 1 - 12606 - CN from Colorcon.

[0021] The ondansetron hydrochloride tablets of the present invention have the following release characteristics: The dissolution medium is a pH 4.5 phosphate medium. After sampling at 10 minutes, the pH value is adjusted to 6.0 with sodium hydroxide solution. The dissolution conditions are the basket method at 20 rpm. The cumulative dissolution at 5 minutes is 6.9% - 19.5%, the cumulative dissolution at 10 minutes is 39.3% - 60.2%, the cumulative dissolution at 15 minutes is 72.1% - 86.4%, and the cumulative dissolution at 20 minutes is 86.2% - 95.5%. In some embodiments, the cumulative dissolution at 5 minutes is 8% - 12%, the cumulative dissolution at 10 minutes is 45.9% - 49.9%, the cumulative dissolution at 15 minutes is 78% - 82%, and the cumulative dissolution at 20 minutes is 93.1% - 96.1%. In some embodiments, the cumulative dissolution at 5 minutes is 9% - 11%, the cumulative dissolution at 10 minutes is 46.9% - 48.9%, the cumulative dissolution at 15 minutes is 79% - 81%, and the cumulative dissolution at 20 minutes is 94.1% - 96.1%.

[0022] In a third aspect, the present invention discloses a method for preparing the ondansetron hydrochloride tablet described in the second aspect above.

[0023] In some embodiments, the preparation method of the ondansetron hydrochloride tablets comprises the following steps: (1) Ondansetron hydrochloride and a part of the first filler are sieved together to obtain a first premix; (2) The remaining first filler and the first premix are sieved together to obtain a second premix; (3) The second filler and the second premix are sieved together to obtain a third premix; (4) The third premix is mixed in a mixer; (5) A lubricant is added for overall mixing, tabletting, and coating.

[0024] In some embodiments, the particle size D of the ondansetron hydrochloride 90 is 30 - 150 μm, and the ondansetron hydrochloride with this particle size can be obtained by pulverization; the particle size D of the microcrystalline cellulose in the second filler 50 is 70 - 130 μm; the pregelatinized starch with a particle size below 150 μm in the second filler accounts for more than 90% of its total mass, and the pregelatinized starch with a particle size above 425 μm accounts for less than 0.5% of its total mass. In step (1), the part of the first filler is 40% - 60% of the total mass of the first filler, such as 50%. In a rotary granulator, the ondansetron hydrochloride raw material and a part of the first filler are sieved together; the rotation speed of the granulator is 800 - 1200 rpm, such as 1000 rpm, and the particle size of the sieve mesh in the granulator is 0.6 - 1.4 mm, such as 1.0 mm.

[0025] In step (2), in a rotary granulator, the remaining first filler and the first premix are sieved together; the rotation speed of the granulator is 600 - 1000 rpm, such as 800 rpm, and the particle size of the sieve mesh in the granulator is 0.6 - 1.4 mm, such as 1.0 mm.

[0026] In step (3), in a rotary granulator, the second filler and the second premix are sieved together; the rotation speed of the granulator is 600 - 1000 rpm, such as 800 rpm, and the particle size of the sieve mesh in the granulator is 0.6 - 1.4 mm, such as 1.0 mm.

[0027] In step (4), in a mixer, the obtained premix is mixed; the rotation speed of the mixing is 10 - 20 rpm, such as 15 rpm, the time is 2 - 7 min, such as 5 min; the loading coefficient of the mixer is 45% - 70%.

[0028] In step (5), in a mixer, a lubricant is added for mixing; the rotation speed of the mixing is 10 - 20 rpm, such as 11 rpm, the time is 1 - 5 min, such as 2 min; the loading coefficient of the mixer is 45% - 70%.

[0029] In step (5), during the tableting process, the ambient humidity is controlled below 65%, such as 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, etc.; during the tableting process, the tablet weight variation is controlled within ±5%, and the hardness is 9.0 - 11.0 kg.

[0030] In step (5), the coating powder is the film coating premix YS - 1 - 12606 - CN of Colorcon.

[0031] Advantageous effects: The stable ondansetron hydrochloride tablets provided by the present invention are composed of an active ingredient ondansetron hydrochloride, a first filler, a second filler, a lubricant, and a coating material. The present invention crushes the active ingredient ondansetron hydrochloride and prepares ondansetron hydrochloride tablets by a direct powder compression process. By using the method of multiple co - sieving for premixing, the mixing uniformity is ensured. Using anhydrous lactose as a filler to reduce the product moisture and ensure the product stability, and using microcrystalline cellulose and pre - gelatinized starch as fillers to ensure good fluidity and compressibility of the total mixed powder, ondansetron hydrochloride tablets with a dissolution curve similar to that of the reference preparation and stable quality are prepared. Compared with the existing process, the present invention has the advantages of simple, fast preparation process, non - sticking punch during tableting, low energy consumption, low product impurities, excellent stability, and good quality. Description of the drawings

[0032] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become clearer.

[0033] Figure 1 Dissolution curves of the preparations obtained in Examples 1-3, the reference preparation, and Comparative Examples 2-3 in a phosphate medium at pH 4.5-6.0. Specific Embodiments

[0034] The present invention can be better understood according to the following examples. However, those skilled in the art can easily understand that the content described in the examples is only used to illustrate the present invention and should not and will not limit the present invention described in detail in the claims.

[0035] Unless otherwise specified, the experimental methods described in the following examples are all conventional methods; unless otherwise specified, the reagents and materials can be obtained from commercial sources.

[0036] In the following examples, the manufacturer of anhydrous lactose is DFE pharma (model: SuperTab 24AN); the manufacturer of pregelatinized starch is Colorcon (model: 2001-NEC). According to the second method in General Rule 0982 of the Chinese Pharmacopoeia, the amount of the sample passing through a sieve with an inner diameter of 150 μm is not less than 90% of the test sample, and the amount of the sample not passing through a sieve with an inner diameter of 425 μm is not more than 0.5%; the D of microcrystalline cellulose PH 112 is 100 μm, and the D of microcrystalline cellulose PH 200 is 180 μm; the manufacturer of magnesium stearate is Anhui Shanhe (model: SH-YM-M), and the D is 5-30 μm; the D of sodium stearyl fumarate is ≤55.0 μm; the coating powder is the film coating premix YS-1-12606-CN of Colorcon Company, and the formulated components are hydroxypropyl methylcellulose, triacetin, titanium dioxide, and yellow iron oxide. 50 is 100 μm, and the D of microcrystalline cellulose PH 200 50 is 180 μm; the manufacturer of magnesium stearate is Anhui Shanhe (model: SH-YM-M), and the D 50 is 5-30 μm; the D of sodium stearyl fumarate 90 ≤55.0 μm; the coating powder is the film coating premix YS-1-12606-CN of Colorcon Company, and the formulated components are hydroxypropyl methylcellulose, triacetin, titanium dioxide, and yellow iron oxide.

[0037] The solid content described in the present invention is in mass percentage.

[0038] The particle sizes of the active pharmaceutical ingredient, filler, and lubricant in the present invention are all detected according to the method for the determination of particle size and particle size distribution in Part IV of the Chinese Pharmacopoeia 2020 Edition (General Rule 0982, Method 3, Dry Method).

[0039] Example 1 The preparation method of ondansetron hydrochloride tablets, when producing 10,00 tablets, includes the following steps: (1) Weighing and pulverizing: Weigh each raw material and auxiliary material according to the weight ratio. Weigh 9.98 parts of ondansetron hydrochloride, 184 parts of anhydrous lactose, 86 parts of microcrystalline cellulose PH112, 32 parts of pregelatinized starch, 1.8 parts of magnesium stearate, and 10 parts of coating powder. The ondansetron hydrochloride raw material is mechanically pulverized, and the particle size D 90 is 30 - 150 μm.

[0040] (2) Premixing 1: The pulverized ondansetron hydrochloride raw material and 50% anhydrous lactose are sieved together in a rotary granulator at a rotational speed of 1000 rpm, and the particle size of the sieve is 1.0 mm to obtain Premix 1.

[0041] (3) Premixing 2: The remaining anhydrous lactose and Premix 1 obtained in step (2) are sieved together in a rotary granulator at a rotational speed of 800 rpm, and the particle size of the sieve is 1.0 mm to obtain Premix 2.

[0042] (4) Premixing 3: Microcrystalline cellulose, pregelatinized starch and Premix 2 obtained in step (3) are sieved together in a rotary granulator at a rotational speed of 800 rpm, and the particle size of the sieve is 1.0 mm to obtain Premix 3.

[0043] (5) Mixing: Premix 3 obtained in step (4) is added to the hopper and mixed in a mixer at a rotational speed of 15 rpm for 5 min; the loading coefficient of the mixer is 60%.

[0044] (6) Final mixing: The intermediate obtained in step (5) is added with magnesium stearate for final mixing at a rotational speed of 11 rpm for 2 min, and the loading coefficient is 60%.

[0045] (7) Tabletting: The final mixed powder obtained in step (6) is loaded into a mold for tabletting. The environmental humidity is 50%, and the tablet weight to be pressed is calculated according to the result of the final mixed powder content, and the tablet weight difference is controlled within ±5%. The hardness is 9.0 - 11.0 kg.

[0046] (8) Coating: Prepare a 10%wt concentration of coating powder Colorcon's film coating premix YS - 1 - 12606 - CN, and place the plain tablets obtained in step (7) in a coating pan for coating, with a coating weight gain of 3% - 4%.

[0047] (9) Packaging: Use polyvinyl chloride / polyvinylidene chloride solid pharmaceutical composite hard sheet and pharmaceutical aluminum foil for packaging.

[0048] Example 2 Same as Example 1, except for the different dosages of each component, which are as follows: Example 2-1: 9.98 parts of ondansetron hydrochloride, 164 parts of anhydrous lactose, 106 parts of microcrystalline cellulose PH112, 32 parts of pregelatinized starch, 1.8 parts of magnesium stearate, 10 parts of coating powder.

[0049] Example 2-2: 9.98 parts of ondansetron hydrochloride, 224 parts of anhydrous lactose, 46 parts of microcrystalline cellulose PH112, 32 parts of pregelatinized starch, 1.8 parts of magnesium stearate, 10 parts of coating powder.

[0050] Example 2-3: 9.98 parts of ondansetron hydrochloride, 194 parts of anhydrous lactose, 97.3 parts of microcrystalline cellulose PH112, 12 parts of pregelatinized starch, 0.5 parts of magnesium stearate, 10 parts of coating powder.

[0051] Example 2-4: 9.98 parts of ondansetron hydrochloride, 162.8 parts of anhydrous lactose, 86 parts of microcrystalline cellulose PH112, 52 parts of pregelatinized starch, 3 parts of magnesium stearate, 10 parts of coating powder.

[0052] Example 3 Same as Example 1, except that 1.8 parts of magnesium stearate in the components are replaced by 1.8 parts of sodium stearyl fumarate.

[0053] Comparative Example 1 Same as Example 1, except that 184 parts of anhydrous lactose in the components are replaced by 184 parts of lactose monohydrate.

[0054] Comparative Example 2 Same as Example 1, except that 86 parts of microcrystalline cellulose PH112 in the components are replaced by 86 parts of microcrystalline cellulose PH200.

[0055] Comparative Example 3 Same as Example 1, except that 86 parts of microcrystalline cellulose PH112 in the components are replaced by 86 parts of low-substituted hydroxypropyl cellulose.

[0056] Comparative Example 4 Same as Example 1, except that 32 parts of pregelatinized starch in the components are replaced by 32 parts of corn starch.

[0057] Experiment 1 The tablets of Example 1, Example 3, Comparative Example 1 and Comparative Example 4 were inspected for tablet appearance and content uniformity. The experimental results are shown in the following table. The results show that the tablets obtained from Example 1 and Example 3 are complete, smooth, with uniform color, no mottles and no foreign matters, and the RSD is 1.16% and 1.31% respectively, and the content uniformity meets the requirements. In Comparative Example 1 and Comparative Example 4, due to sticking during tableting, the surface of the plain tablets is incomplete and defective, and the appearance inspection is unqualified. At the same time, the content uniformity becomes poor.

[0058] The content uniformity of the above Example 2 was determined. The experimental results showed that the RSD of the determination results of the Example 2 samples was 1.1% - 1.7%, the content uniformity met the requirements, and the appearance inspection of the tablets met the requirements.

[0059] Table 1 Appearance and content uniformity of tablets in each group / (%)

[0060] Test 2 The dissolution curves of the samples prepared from Example 1, Example 2, Example 3, the reference preparation, Comparative Example 2, and Comparative Example 3 were determined. The dissolution medium was selected as pH 4.5 phosphate medium. After sampling at 10 minutes, sodium hydroxide solution was added to adjust the pH value to 6.0. The dissolution conditions were selected as the basket method at 20 rpm, and the first method (basket method) in the "Chinese Pharmacopoeia" for the determination of dissolution and release was used to measure at 37°C. The experimental results are shown in Table 2 and Figure 1 As shown, the dissolution curves of the samples prepared from Example 1, Example 2, and Example 3 of the present invention were similar to the reference preparation, and the F2 value was greater than 50. In Comparative Example 2, the model of microcrystalline cellulose was changed to PH200, and the dissolution rate of the preparation obtained in Comparative Example 2 became slower and was not similar to the reference, with the F2 value less than 50. After the microcrystalline cellulose in Comparative Example 3 was replaced with low-substituted hydroxypropyl cellulose, the dissolution rate of the preparation obtained in Comparative Example 3 became faster and was not similar to the reference, with the F2 value less than 50.

[0061] Table 2 Dissolution rates (%) of the preparations obtained from Examples 1 - 3, the reference preparation, Comparative Example 2, and Comparative Example 3

[0062] Test 3 The coated tablets prepared from the above Example 1 and Comparative Example 1 were simultaneously subjected to stress testing (high temperature 60°C, high humidity RH75%, light 4500 ± 500 lux / h, 90 μW / cm 2) Placement (naked placement) study, comparison of related substances and content. The liquid phase method adopts the method in the Chinese Pharmacopoeia: Determination is carried out according to the high performance liquid chromatography method (General Principles 0512 of the Chinese Pharmacopoeia 2020 Edition). Test solution: Take an appropriate amount of the fine powder of this product (equivalent to about 4 mg of ondansetron), place it in a 10-ml volumetric flask, add the mobile phase to dissolve ondansetron hydrochloride and dilute to the mark, shake well, filter, and take the subsequent filtrate. Control solution: Accurately measure 1 ml of the test solution, place it in a 100-ml volumetric flask, and dilute to the mark with the mobile phase, shake well. Chromatographic conditions: Use cyanopropylsilane-bonded silica gel as the filler; use 0.02 mol / L sodium dihydrogen phosphate solution (adjust the pH value to 5.4 with sodium hydroxide test solution)-acetonitrile (50:50) as the mobile phase; the detection wavelength is 216 nm; the injection volume is 10 μl. System suitability requirements: The number of theoretical plates calculated based on the ondansetron peak is not less than 2000. Determination method: Accurately measure the test solution and the control solution, and inject them into the liquid chromatograph respectively, and record the chromatogram until 4 times the retention time of the main component peak.

[0063] The results show that the properties of the products in Example 1 and Comparative Example 1 at each time point are similar, both are film-coated tablets, showing white or almost white after removing the coating. The change trend of related substances in Example 1 is significantly better than that in Comparative Example 1 on the 15th day and the 30th day. See Table 3 below, where the impurities B-F are recorded in the ondansetron hydrochloride part of the British Pharmacopoeia.

[0064] Table 3

[0065] Other examples and comparative examples were detected according to Test 3, and the results are shown in Table 4. The impurities in Example 2 with changed component dosage, Example 3 with the lubricant replaced by sodium stearyl fumarate, Comparative Example 2 with the microcrystalline cellulose model replaced, Comparative Example 3 with microcrystalline cellulose replaced by low-substituted hydroxypropyl cellulose, and Comparative Example 4 with pregelatinized starch replaced by corn starch were not significantly affected.

[0066] Impurity content of each group / (%)

[0067] The above examples only represent several implementation modes of the present invention, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several deformations and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the invention patent should be subject to the appended claims.

Claims

1. An ondansetron hydrochloride composition, characterized in that The composition comprises the following components in parts by weight: Ondansetron hydrochloride 8-12 parts 158-228 parts of the first filler Second filler 68-142 parts Lubricant 0.1-7 parts Coating powder 5-15 parts The first filler is anhydrous lactose, and the second filler is microcrystalline cellulose and pregelatinized starch.

2. The ondansetron hydrochloride composition according to claim 1, characterized in that The weight parts of each component are as follows: Ondansetron hydrochloride 9.98 parts 160-226 parts of the first filler Second filler 72-140 parts Lubricant 0.3-5 parts 5-15 parts of coating powder.

3. The ondansetron hydrochloride composition according to claim 1, characterized in that The weight parts of each component are as follows: Ondansetron hydrochloride 9.98 parts 162-224 parts of the first filler Second filler 76-138 parts Lubricant 0.5-3 parts Coating powder 8-12 parts The content of microcrystalline cellulose in the second filler is 55-95%wt.

4. The ondansetron hydrochloride composition according to any one of claims 1 to 3, characterized in that The lubricant is selected from magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate or any combination thereof.

5. The ondansetron hydrochloride composition according to any one of claims 1 to 3, characterized in that The particle size D of the ondansetron hydrochloride 90 The particle size D of the microcrystalline cellulose in the second filler is 30-150 μm; 50 The pregelatinized starch in the second filler has a particle size of less than 150 μm, which accounts for more than 90% of its total mass, and a particle size of more than 425 μm, which accounts for less than 0.5% of its total mass.

6. A method for preparing ondansetron hydrochloride tablets, characterized in that: The composition according to any one of claims 1 to 5 is prepared by a powder direct compression method.

7. The preparation method according to claim 6, characterized in that: The preparation method comprises the following preparation steps: (1) sieving ondansetron hydrochloride and a portion of the first filler to obtain a first premix; (2) sieving the remaining first filler and the first premix to obtain a second premix; (3) sieving the second filler and the second premix to obtain a third premix; (4) mixing the third premix in a mixer; (5) Add lubricant for overall mixing, tableting, and coating; In step (1), the portion of the first filler is 40%-60% of the total mass of the first filler.

8. The preparation method according to claim 7, characterized in that: In step (1), the co-sieving is co-sieving in a rotary granulator; the rotation speed of the rotary granulator is 800-1200 rpm, and the particle size of the sieve in the rotary granulator is 0.6-1.4 mm; In step (2), the co-sieving is co-sieving in a rotary granulator; the rotation speed of the rotary granulator is 600-1000 rpm, and the particle size of the sieve in the rotary granulator is 0.6-1.4 mm; In step (3), the co-sieving is co-sieving in a rotary granulator; the rotation speed of the rotary granulator is 600-1000 rpm, and the particle size of the sieve in the rotary granulator is 0.6-1.4 mm; In step (4), the third premix is ​​mixed in a mixer; the mixing speed is 10-20 rpm, the mixing time is 2-7 min; the charging factor of the mixer is 45%-70%; In step (5), a lubricant is added to a mixer for mixing; the mixing speed is 10-20 rpm, and the mixing time is 1-5 min; and the loading factor of the mixer is 45%-70%.

9. An ondansetron hydrochloride tablet, characterized in that: Made by the method described in any one of claims 6 to 8.

10. The ondansetron hydrochloride tablet according to claim 9, characterized in that: The ondansetron hydrochloride tablets have the following release characteristics: The dissolution medium used was pH 4.5 phosphate medium. After sampling at 10 minutes, sodium hydroxide solution was added to adjust the pH value to 6.

0. The dissolution condition used was the basket method at 20rpm. The cumulative dissolution rate was 6.9%-19.5% in 5 minutes, 39.3%-60.2% in 10 minutes, 72.1%-86.4% in 15 minutes, and 86.2%-95.5% in 20 minutes.

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