A method for preparing desloratadine tablets

Abstract

The present application relates to a kind of preparation methods of desloratadine tablets, which includes pre-gelatinized starch slurry and desloratadine mixing, fluidized bed granulation, whole grain, total mixing, tabletting, coating and the like steps.The present application precisely controls the key process parameters in preparation process, so that the impurity content of product is less, and the product quality is improved.The preparation process of the method of the present application is relatively simple, easy to operate, easy to popularize and apply, and the formula of the method is relatively simple, and the cost is controllable.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a method for preparing desloratadine tablets. Background Technology

[0002] Desloratadine, chemical name: 8-chloro-6,11-dihydro-11-(4-piperidinyl)-5H-benzo[5,6]-cycloheptano[1,2-b]pyridine, structural formula: Molecular formula: C 19 H 19 ClN2, molecular weight: 310.82. Desloratadine is the active metabolite of loratadine, originally developed by Sepracor in the United States, and marketed under various brand names. and

[0003] Desloratadine is a secondary amine compound that is sensitive to high temperatures, high humidity, acidity, and sugars (stearic acid, lactose, etc.), readily producing impurities such as formyl-based loratadine. These conditions are often unavoidable during tablet manufacturing. Researchers have attempted to reduce the impact of acidic excipients or sugars on desloratadine by adding alkaline salts and resins; however, the addition of these excipients increases production costs and has limited effectiveness. Summary of the Invention

[0004] In view of the shortcomings of the prior art, the present invention provides a method for preparing desloratadine tablets.

[0005] The technical solution of this invention is as follows:

[0006] A method for preparing desloratadine tablets includes the following steps:

[0007] ① Add 70%–76% of the prescribed amount of water to the mixing tank, add pregelatinized starch, and prepare a pregelatinized starch slurry; add desloratadine to the mixing tank, and after the addition is complete, continue stirring and sieve; maintain stirring.

[0008] ② Fluidized bed granulation:

[0009] Preheating: Divide the microcrystalline cellulose into two parts, namely microcrystalline cellulose A and microcrystalline cellulose B; add microcrystalline cellulose A and calcium hydrogen phosphate dihydrate into the fluidized bed granulation dryer in sequence, preheat the material to 50-55℃ and then start granulation;

[0010] Granulation: The liquid material obtained in step ① is atomized by a nozzle and sprayed onto the powder in a fluidized state. The droplets come into contact with the powder to form particle nuclei. At the same time, the continuously sprayed droplets fall onto the particle nuclei to produce an adhesive bridging effect, so that the particles and particle nuclei, and the particles themselves, combine with each other to gradually form larger particles.

[0011] The granulation conditions are as follows: atomization pressure 0.1-0.3 MPa, turn on the spray gun for granulation, control the liquid supply rate 50-150 rpm, and keep the liquid obtained in step ① under stirring during the granulation process;

[0012] After granulation, the pellets are dried.

[0013] ③ Whole grains;

[0014] ④ General mixing: Add the granulated granules, microcrystalline cellulose B, corn starch and talc to the mixer in sequence and mix. After mixing, discharge the mixture.

[0015] ⑤ Tableting: Control the hardness of the unprocessed tablets to 4.5–8 kg;

[0016] ⑥ Coating: Add the remaining water from the prescription to the mixing tank, turn on the compressed air, and add the components of the film coating premix while stirring. After the addition is complete, continue stirring. Place the uncoated tablets in the coating pan and preheat to a tablet bed temperature of 40-50℃. Coat the tablets, controlling the tablet bed temperature at 35-55℃ during the coating process. Dry the tablets after coating. After drying, turn off the heating and wait until the tablet bed temperature is ≤35℃ before removing the tablets.

[0017] Preferably, the formulation also includes glycerin.

[0018] Preferably, glycerol is added in step ①, step ④, or step ⑥.

[0019] This invention further improves the preparation method of desloratadine tablets, which includes the following steps:

[0020] ① Divide the microcrystalline cellulose into two portions, namely microcrystalline cellulose A and microcrystalline cellulose B; add 70%–76% of the prescribed amount of water to a mixing tank, add pregelatinized starch to prepare a pregelatinized starch slurry, add microcrystalline cellulose B and calcium hydrogen phosphate dihydrate, heat at 80–150 r / min and 80–85℃ for 30–45 min, then add glycerol and stir for 1–1.5 h, let stand and cool to below 40℃; add desloratadine to the mixing tank, after the addition is complete, continue stirring; sieve; maintain stirring.

[0021] ② Fluidized bed granulation:

[0022] Preheating: Add microcrystalline cellulose A to the fluidized bed granulation dryer and preheat the material to 50-55°C before starting granulation;

[0023] The granulation conditions are as follows: atomization pressure 0.1-0.3 MPa, turn on the spray gun for granulation, control the liquid supply rate 50-150 rpm, and keep the liquid obtained in step ① under stirring during the granulation process;

[0024] After granulation, the pellets are dried.

[0025] ③ Whole grains;

[0026] ④ Total Mixing:

[0027] Add the granulated granules, corn starch, and talcum powder to the mixer in sequence, seal the container, mix, and then discharge the mixture after mixing is complete.

[0028] ⑤ Tableting: Tableting is performed using a tablet press, with the hardness of the raw tablets controlled at 4.5-8 kg.

[0029] No stratification occurred during the total particle transport and tableting process.

[0030] ⑥ Coating: Add the remaining water from the prescription to the mixing tank, turn on the compressed air, and add the components of the film coating premix while stirring. After the addition is complete, continue stirring. Place the uncoated tablets in the coating pan and preheat to a tablet bed temperature of 40-50℃. Coat the tablets, controlling the tablet bed temperature at 35-55℃ during the coating process. Dry the tablets after coating. After drying, turn off the heating and wait until the tablet bed temperature is ≤35℃ before removing the tablets.

[0031] Preferably, the film coating premix comprises hydroxypropyl methylcellulose, lactose, titanium dioxide, polyethylene glycol 600, and colorant.

[0032] Preferably, the formulation of the desloratadine tablets is as follows:

[0033] Tablet core: 5-6 parts by weight of desloratadine, 50-53 parts by weight of dicalcium phosphate dihydrate, 3-5 parts by weight of corn starch, 4-5 parts by weight of pregelatinized starch, 11-17 parts by weight of microcrystalline cellulose A, 10-14 parts by weight of microcrystalline cellulose B, 8-10 parts by weight of talc, and 0-4 parts by weight of glycerin.

[0034] Film coating premix: 1-1.5 parts by weight of hydroxypropyl methylcellulose, 1.5-2 parts by weight of lactose, 1-2 parts by weight of titanium dioxide, 0.7-1.7 parts by weight of polyethylene glycol 600, 0.3-1 parts by weight of colorant, and 0-4 parts by weight of glycerin.

[0035] Preferably, the formulation of the desloratadine tablets is as follows:

[0036] Tablet core: 5.0 parts by weight of desloratadine, 53 parts by weight of calcium hydrogen phosphate dihydrate, 3 parts by weight of corn starch, 4 parts by weight of pregelatinized starch, 13 parts by weight of microcrystalline cellulose A, 14 parts by weight of microcrystalline cellulose B, 8 parts by weight of talc, and 2 parts by weight of glycerin.

[0037] Film coating premix: 1 part by weight hydroxypropyl methylcellulose, 1.5 parts by weight lactose, 1 part by weight titanium dioxide, 1.7 parts by weight polyethylene glycol 600, and 0.3 parts by weight colorant.

[0038] Compared with the prior art, the beneficial results of the present invention are as follows:

[0039] This invention first optimizes the excipient formulation, which is suitable for fluidized bed wet granulation. Furthermore, this invention divides the excipients into internal and external additives, adding them step-by-step, and precisely controlling key process parameters during preparation, resulting in fewer impurities generated under granulation conditions of approximately 50°C.

[0040] In a further optimized version, the present invention adds microcrystalline cellulose B and calcium hydrogen phosphate dihydrate to the pregelatinized starch slurry, heats it at 80-150 r / min and 80-85°C for 30-45 min, then adds glycerol and stirs for 1-1.5 h, resulting in a slurry with good film-forming properties. Mixing this slurry with desloratadine provides a certain barrier protection effect, and the modified slurry can also act as an adhesion modifier, improving the contact between the mixture and excipients and coatings. Desloratadine tablets processed using this method have a lower impurity content. Detailed Implementation

[0041] To enable those skilled in the art to better understand the technical content of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0042] Several preferred formulations are provided below, along with explanations of their preparation effects in conjunction with the preparation methods.

[0043]

[0044]

[0045] Note: Each tablet (deloratadine): 5mg

[0046] Example 1 – Preparation process of desloratadine tablets

[0047] This embodiment uses the formulation of prescription 1.

[0048] ① Add 76% of the prescribed amount of purified water to the mixing tank. Adjust the stirring speed to quickly disperse the powder in the vortex without splashing. Use a spatula to slowly and evenly add the prescribed amount of pregelatinized starch, controlling the addition time to about 10 minutes. Stir to prepare a pregelatinized starch slurry. Slowly add the prescribed amount of desloratadine to the mixing tank. During the addition process, control the stirring speed to quickly disperse the powder in the vortex. After the addition is complete, control the stirring speed to create a vortex in the liquid and continue stirring for about 30 minutes. Pass through a 40-mesh sieve. Maintain the stirring state.

[0049] ② Fluidized bed granulation:

[0050] Preheating: Microcrystalline cellulose A and dicalcium phosphate dihydrate are added sequentially to the fluidized bed granulation dryer. The materials are preheated to 50-55°C before granulation begins.

[0051] Granulation:

[0052] The granulation conditions are as follows: atomization pressure 0.1MPa, granulation is performed by turning on the spray gun, the liquid supply rate is controlled at 150rpm, and the liquid obtained in step ① is kept in a stirring state during the granulation process.

[0053] Drying: After granulation, turn off the spray gun atomization and protective gas, and start drying until the material moisture content is ≤2.0%.

[0054] ③ Whole grains:

[0055] Granulation is performed using a high-speed granulator with a screen aperture of [missing information].

[0056] ④ Total Mixing:

[0057] Add the granulated granules, microcrystalline cellulose B, corn starch and talc to the mixer in sequence, seal the mixer, set the mixing speed to 10 rpm, and mix for 900 seconds (mixing for 900 seconds can ensure uniform mixing). After mixing is completed, discharge the material.

[0058] ⑤ Tableting: Tableting is performed using a tablet press, with the hardness of the raw tablet controlled at 4.5 kg.

[0059] No stratification occurred during the total particle transport and tableting process.

[0060] ⑥ Coating:

[0061] Preparation of coating solution: Add the remaining purified water from the prescription to the mixing tank, turn on the compressed air, and slowly add each component of the film coating premix while stirring. After the addition is complete, continue stirring for at least 45 minutes. Place the uncoated tablets in the coating pan, preheat to a tablet bed temperature of 40–50°C, and then perform coating. During the coating process, control the tablet bed temperature at 35–55°C. After coating, dry for 5–15 minutes. After drying, turn off the heating and wait until the tablet bed temperature is ≤35°C before unloading the tablets.

[0062] ⑦ Aluminum-plastic packaging: The inner packaging uses aluminum foil for pharmaceutical packaging and solid pharmaceutical composite rigid sheets formed by cold stamping of polyamide / aluminum / polyvinyl chloride.

[0063] Example 2 – Preparation process of desloratadine tablets

[0064] This embodiment uses the formulation of prescription 1.

[0065] ① Add 70% of the prescribed amount of purified water to the mixing tank. Adjust the stirring speed to quickly disperse the powder in the vortex without splashing. Use a spatula to slowly and evenly add the prescribed amount of pregelatinized starch, controlling the addition time to about 10 minutes. Stir to prepare a pregelatinized starch slurry. Slowly add the prescribed amount of desloratadine to the mixing tank. During the addition process, control the stirring speed to quickly disperse the powder in the vortex. After the addition is complete, control the stirring speed to create a vortex in the liquid and continue stirring for about 30 minutes. Pass through a 40-mesh sieve. Maintain the stirring state.

[0066] ② Fluidized bed granulation:

[0067] Preheating: Microcrystalline cellulose A and dicalcium phosphate dihydrate are added sequentially to the fluidized bed granulation dryer. The materials are preheated to 50-55°C before granulation begins.

[0068] Granulation:

[0069] The granulation conditions are as follows: atomization pressure 0.3MPa, granulation is performed by turning on the spray gun, the liquid supply rate is controlled at 50rpm, and the liquid obtained in step ① is kept in a stirring state during the granulation process.

[0070] Drying: After granulation, turn off the spray gun atomization and protective gas, and start drying until the material moisture content is ≤2.0%.

[0071] ③ Whole grains:

[0072] Granulation is performed using a high-speed granulator with a screen aperture of [missing information].

[0073] ④ Total Mixing:

[0074] Add the granulated granules, microcrystalline cellulose B, corn starch and talc to the mixer in sequence, seal the mixer, set the mixing speed to 10 rpm, and mix for 900 seconds (mixing for 900 seconds can ensure uniform mixing). After mixing is completed, discharge the material.

[0075] ⑤ Tableting: Tableting is performed using a tablet press, and the hardness of the raw tablets is controlled at 8kg.

[0076] No stratification occurred during the total particle transport and tableting process.

[0077] ⑥ Coating:

[0078] Preparation of coating solution: Add the remaining purified water from the prescription to the mixing tank, turn on the compressed air, and slowly add each component of the film coating premix while stirring. After the addition is complete, continue stirring for at least 45 minutes. Place the uncoated tablets in the coating pan, preheat to a tablet bed temperature of 40–50°C, and then perform coating. During the coating process, control the tablet bed temperature at 35–55°C. After coating, dry for 5–15 minutes. After drying, turn off the heating and wait until the tablet bed temperature is ≤35°C before unloading the tablets.

[0079] ⑦ Aluminum-plastic packaging: The inner packaging uses aluminum foil for pharmaceutical packaging and solid pharmaceutical composite rigid sheets formed by cold stamping of polyamide / aluminum / polyvinyl chloride.

[0080] Example 3 – Preparation process of desloratadine tablets

[0081] This embodiment uses Formula 2.

[0082] ① Add 76% of the prescribed amount of purified water to the mixing tank. Adjust the stirring speed to quickly disperse the powder in the vortex without splashing. Use a spatula to slowly and evenly add the prescribed amount of pregelatinized starch, controlling the addition time to about 10 minutes. Stir to prepare a pregelatinized starch slurry. Slowly add the prescribed amount of desloratadine to the mixing tank. During the addition process, control the stirring speed to quickly disperse the powder in the vortex. After the addition is complete, control the stirring speed to create a vortex in the liquid and continue stirring for about 30 minutes. Pass through a 40-mesh sieve. Maintain the stirring state.

[0083] ② Fluidized bed granulation:

[0084] Preheating: Microcrystalline cellulose A and dicalcium phosphate dihydrate are added sequentially to the fluidized bed granulation dryer. The materials are preheated to 50-55°C before granulation begins.

[0085] Granulation:

[0086] The granulation conditions are as follows: atomization pressure 0.1MPa, granulation is performed by turning on the spray gun, the liquid supply rate is controlled at 150rpm, and the liquid obtained in step ① is kept in a stirring state during the granulation process.

[0087] Drying: After granulation, turn off the spray gun atomization and protective gas, and start drying until the material moisture content is ≤2.0%.

[0088] ③ Whole grains:

[0089] Granulation is performed using a high-speed granulator with a screen aperture of [missing information].

[0090] ④ Total Mixing:

[0091] Add the granulated granules, microcrystalline cellulose B, corn starch and talc to the mixer in sequence, seal the mixer, set the mixing speed to 10 rpm, and mix for 900 seconds (mixing for 900 seconds can ensure uniform mixing). After mixing is completed, discharge the material.

[0092] ⑤ Tableting: Tableting is performed using a tablet press, with the hardness of the raw tablet controlled at 4.5 kg.

[0093] No stratification occurred during the total particle transport and tableting process.

[0094] ⑥ Coating:

[0095] Preparation of coating solution: Add the remaining purified water from the prescription to the mixing tank, turn on the compressed air, and slowly add each component of the film coating premix while stirring. After the addition is complete, continue stirring for at least 45 minutes. Place the uncoated tablets in the coating pan, preheat to a tablet bed temperature of 40–50°C, and then perform coating. During the coating process, control the tablet bed temperature at 35–55°C. After coating, dry for 5–15 minutes. After drying, turn off the heating and wait until the tablet bed temperature is ≤35°C before unloading the tablets.

[0096] ⑦ Aluminum-plastic packaging: The inner packaging uses aluminum foil for pharmaceutical packaging and solid pharmaceutical composite rigid sheets formed by cold stamping of polyamide / aluminum / polyvinyl chloride.

[0097] Example 4 – Preparation process of desloratadine tablets

[0098] This embodiment uses prescription 3.

[0099] ① Add 76% of the prescribed amount of purified water to the mixing tank. Adjust the stirring speed to quickly disperse the powder in the vortex without splashing. Use a spatula to slowly and evenly add the prescribed amount of pregelatinized starch, controlling the addition time to about 10 minutes. Stir to prepare a pregelatinized starch slurry. Slowly add the prescribed amount of desloratadine to the mixing tank. During the addition process, control the stirring speed to quickly disperse the powder in the vortex. After the addition is complete, control the stirring speed to create a vortex in the liquid and continue stirring for about 30 minutes. Pass through a 40-mesh sieve. Maintain the stirring state.

[0100] ② Fluidized bed granulation:

[0101] Preheating: Microcrystalline cellulose A and dicalcium phosphate dihydrate are added sequentially to the fluidized bed granulation dryer. The materials are preheated to 50-55°C before granulation begins.

[0102] Granulation:

[0103] The granulation conditions are as follows: atomization pressure 0.1MPa, granulation is performed by turning on the spray gun, the liquid supply rate is controlled at 150rpm, and the liquid obtained in step ① is kept in a stirring state during the granulation process.

[0104] Drying: After granulation, turn off the spray gun atomization and protective gas, and start drying until the material moisture content is ≤2.0%.

[0105] ③ Whole grains:

[0106] Granulation is performed using a high-speed granulator with a screen aperture of [missing information].

[0107] ④ Total Mixing:

[0108] Add the granulated granules, microcrystalline cellulose B, corn starch, glycerin and talc to the mixer in sequence, seal the mixer, set the mixing speed to 10 rpm, and mix for 900 seconds (mixing for 900 seconds can ensure uniform mixing). After mixing is completed, discharge the material.

[0109] ⑤ Tableting: Tableting is performed using a tablet press, with the hardness of the raw tablet controlled at 4.5 kg.

[0110] No stratification occurred during the total particle transport and tableting process.

[0111] ⑥ Coating:

[0112] Preparation of coating solution: Add the remaining purified water from the prescription to the mixing tank, turn on the compressed air, and slowly add each component of the film coating premix while stirring. After the addition is complete, continue stirring for at least 45 minutes. Place the uncoated tablets in the coating pan, preheat to a tablet bed temperature of 40–50°C, and then perform coating. During the coating process, control the tablet bed temperature at 35–55°C. After coating, dry for 5–15 minutes. After drying, turn off the heating and wait until the tablet bed temperature is ≤35°C before unloading the tablets.

[0113] ⑦ Aluminum-plastic packaging: The inner packaging uses aluminum foil for pharmaceutical packaging and solid pharmaceutical composite rigid sheets formed by cold stamping of polyamide / aluminum / polyvinyl chloride.

[0114] Example 5 – Preparation process of desloratadine tablets

[0115] This embodiment uses prescription 3.

[0116] ① Add 76% of the prescribed amount of purified water to the mixing tank. Adjust the stirring speed to ensure the powder is quickly dispersed in the vortex without splashing. Slowly and evenly add the prescribed amount of pregelatinized starch using a spatula, controlling the addition time to about 10 minutes. Stir to prepare a pregelatinized starch slurry. Add microcrystalline cellulose B and calcium hydrogen phosphate dihydrate. Heat at 80-150 r / min (preferably 150 rpm) and 80-85℃ (preferably 80℃) for 30-45 minutes (preferably 30 minutes). Then add glycerol and stir for 1-1.5 hours (preferably 1 hour). Let it stand and cool to below 40℃. Slowly add the prescribed amount of desloratadine to the mixing tank. During the addition process, control the stirring speed to ensure the powder is quickly dispersed in the vortex. After the addition is complete, control the stirring speed to create a vortex in the liquid and continue stirring for about 30 minutes. Pass through a 40-mesh sieve. Maintain stirring.

[0117] ② Fluidized bed granulation:

[0118] Preheating: Add microcrystalline cellulose A to the fluidized bed granulation dryer and preheat the material to 50-55°C before starting granulation.

[0119] Granulation:

[0120] The granulation conditions are as follows: atomization pressure 0.1MPa, granulation is performed by turning on the spray gun, the liquid supply rate is controlled at 150rpm, and the liquid obtained in step ① is kept in a stirring state during the granulation process.

[0121] Drying: After granulation, turn off the spray gun atomization and protective gas, and start drying until the material moisture content is ≤2.0%.

[0122] ③ Whole grains:

[0123] Granulation is performed using a high-speed granulator with a screen aperture of [missing information].

[0124] ④ Total Mixing:

[0125] Add the granulated granules, corn starch, and talcum powder to the mixer in sequence, seal the machine, set the mixing speed to 10 rpm, and mix for 900 seconds (mixing for 900 seconds ensures uniform mixing). After mixing is complete, discharge the mixture.

[0126] ⑤ Tableting: Tableting is performed using a tablet press, with the hardness of the raw tablet controlled at 4.5 kg.

[0127] No stratification occurred during the total particle transport and tableting process.

[0128] ⑥ Coating:

[0129] Preparation of coating solution: Add the remaining purified water from the prescription to the mixing tank, turn on the compressed air, and slowly add each component of the film coating premix while stirring. After the addition is complete, continue stirring for at least 45 minutes. Place the uncoated tablets in the coating pan, preheat to a tablet bed temperature of 40–50°C, and then perform coating. During the coating process, control the tablet bed temperature at 35–55°C. After coating, dry for 5–15 minutes. After drying, turn off the heating and wait until the tablet bed temperature is ≤35°C before unloading the tablets.

[0130] ⑦ Aluminum-plastic packaging: The inner packaging uses aluminum foil for pharmaceutical packaging and solid pharmaceutical composite rigid sheets formed by cold stamping of polyamide / aluminum / polyvinyl chloride.

[0131] Example 6 – Preparation process of desloratadine tablets

[0132] This embodiment uses the formulation of prescription 1.

[0133] ① Add 76% of the prescribed amount of purified water to the mixing tank. Adjust the stirring speed to quickly disperse the powder in the vortex without splashing. Use a spatula to slowly and evenly add the prescribed amount of pregelatinized starch, controlling the addition time to about 10 minutes. Stir to prepare a pregelatinized starch slurry. Slowly add the prescribed amount of desloratadine to the mixing tank. During the addition process, control the stirring speed to quickly disperse the powder in the vortex. After the addition is complete, control the stirring speed to create a vortex in the liquid and continue stirring for about 30 minutes. Pass through a 40-mesh sieve. Maintain the stirring state.

[0134] ② Fluidized bed granulation:

[0135] Preheating: Microcrystalline cellulose A, calcium hydrogen phosphate dihydrate, microcrystalline cellulose B, corn starch and talc are added to the fluidized bed granulation dryer in sequence. The materials are preheated to 50-55°C before granulation begins.

[0136] Granulation:

[0137] The granulation conditions are as follows: atomization pressure 0.1MPa, granulation is performed by turning on the spray gun, the liquid supply rate is controlled at 150rpm, and the liquid obtained in step ① is kept in a stirring state during the granulation process.

[0138] Drying: After granulation, turn off the spray gun atomization and protective gas, and start drying until the material moisture content is ≤2.0%.

[0139] ③ Whole grains:

[0140] Granulation is performed using a high-speed granulator with a screen aperture of [missing information].

[0141] ④ Tableting: Tableting is performed using a tablet press, and the hardness of the raw tablets is controlled at 4.5 kg.

[0142] No stratification occurred during the total particle transport and tableting process.

[0143] ⑤ Coating:

[0144] Preparation of coating solution: Add the remaining purified water from the prescription to the mixing tank, turn on the compressed air, and slowly add each component of the film coating premix while stirring. After the addition is complete, continue stirring for at least 45 minutes. Place the uncoated tablets in the coating pan, preheat to a tablet bed temperature of 40–50°C, and then perform coating. During the coating process, control the tablet bed temperature at 35–55°C. After coating, dry for 5–15 minutes. After drying, turn off the heating and wait until the tablet bed temperature is ≤35°C before unloading the tablets.

[0145] ⑥ Aluminum-plastic packaging: The inner packaging uses aluminum foil for pharmaceutical packaging and solid pharmaceutical composite rigid sheets formed by cold stamping of polyamide / aluminum / polyvinyl chloride.

[0146] Sample testing

[0147] Three batches of samples were prepared according to the methods of each of the above embodiments. Commercially available tablets were used as a reference, and impurities were detected by high-performance liquid chromatography (HPLC). The chromatographic conditions were as follows: C18 column; mobile phase: 0.06 mol / L potassium dihydrogen phosphate solution (pH adjusted to 3.3 with phosphoric acid) – acetonitrile – methanol (60:25:15); flow rate: 1.0 mL / min; column temperature: 30 °C; detection wavelength: 236 nm; injection volume: 20 μL. The test solution and impurity reference solution were injected separately into the HPLC system, and the chromatograms were recorded. The impurity content was calculated based on peak area using the external standard method. The detection results are shown in the table below:

[0148] Loratadine with formyl base Other largest single hybrids Total impurities Reference formulation (trade name: AERIUS) 0.077％～0.086％ 0.037％～0.040％ 0.132％～0.136％ Example 1 0.011％～0.012％ 0.031％～0.033％ 0.080％～0.085％ Example 2 0.010％～0.011％ 0.030％～0.032％ 0.082％～0.086％ Example 3 0.011％～0.012％ 0.030％～0.031％ 0.085％～0.088％ Example 4 0.011％～0.012％ 0.030％～0.032％ 0.081％～0.083％ Example 5 Not detected 0.016％～0.021％ 0.025％～0.031％ Example 6 0.030％～0.033％ 0.042％～0.047％ 0.102％～0.107％

[0149] The results showed that the self-made tablets of the present invention had low impurity content. The formyl-based loratadine and total impurity content of Examples 1 to 6 were significantly lower than those of the reference preparation, with Example 5 showing the best effect.

[0150] Other notes: Dissolution rate, moisture content, and other properties were tested. The self-made formulations were basically the same as the reference formulations.

[0151] The above description is only a partial embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing desloratadine tablets, characterized in that, Includes the following steps: ① Add 70%~76% of the prescribed amount of water to the mixing tank, add pregelatinized starch, and prepare a pregelatinized starch slurry; add desloratadine to the mixing tank, and after the addition is complete, continue stirring and sieve; maintain stirring. ② Fluidized bed granulation: Preheating: Divide the microcrystalline cellulose into two portions, namely microcrystalline cellulose A and microcrystalline cellulose B; add microcrystalline cellulose A and calcium hydrogen phosphate dihydrate into the fluidized bed granulation dryer in sequence, preheat the material to 50~55℃ and then start granulation; Granulation: The liquid material obtained in step ① is atomized by a nozzle and sprayed onto the powder in a fluidized state; The granulation conditions are as follows: atomization pressure 0.1~0.3MPa, turn on the spray gun for granulation, control the liquid supply rate 50~150rpm, and keep the liquid obtained in step ① in a stirring state during the granulation process; After granulation, the pellets are dried. ③ Whole grains; ④ General mixing: Add the granulated granules, microcrystalline cellulose B, corn starch and talc to the mixer in sequence and mix. After mixing, discharge the mixture. ⑤ Tableting: Control the hardness of the unprocessed tablets to 4.5–8 kg; ⑥ Coating: Add the remaining water from the prescription to the mixing tank, turn on the compressed air, and add the components of the film coating premix while stirring. After the addition is complete, continue stirring. Place the uncoated tablets in the coating pan and preheat to a tablet bed temperature of 40-50℃. Coat the tablets, controlling the tablet bed temperature at 35-55℃ during the coating process. Dry the tablets after coating. After drying, turn off the heating and wait until the tablet bed temperature is ≤35℃ before unloading the tablets. The formulation of the desloratadine tablets is as follows: Core ingredients: 5-6 parts by weight of desloratadine, 50-53 parts by weight of dicalcium phosphate dihydrate, 3-5 parts by weight of corn starch, 4-5 parts by weight of pregelatinized starch, 11-17 parts by weight of microcrystalline cellulose A, 10-14 parts by weight of microcrystalline cellulose B, 8-10 parts by weight of talc, 0-4 parts by weight of glycerin; Film coating premix: 1-1.5 parts by weight of hydroxypropyl methylcellulose, 1.5-2 parts by weight of lactose, 1-2 parts by weight of titanium dioxide, 0.7-1.7 parts by weight of polyethylene glycol 600, 0.3-1 parts by weight of colorant, and 0-4 parts by weight of glycerin; glycerin is added in step ①, step ④, or step ⑥.

2. A method for preparing desloratadine tablets, characterized in that, Includes the following steps: ① Divide the microcrystalline cellulose into two portions, namely microcrystalline cellulose A and microcrystalline cellulose B; add 70%~76% of the prescribed amount of water to the mixing tank, add pregelatinized starch to prepare a pregelatinized starch slurry, add microcrystalline cellulose B and calcium hydrogen phosphate dihydrate, heat at 80~150 r / min and 80~85℃ for 30~45 min, then add glycerol and stir for 1~1.5 h, let stand and cool down to below 40℃; add desloratadine to the mixing tank, after the addition is complete, continue stirring; sieve; maintain stirring. ② Fluidized bed granulation: Preheating: Add microcrystalline cellulose A to the fluidized bed granulation dryer and preheat the material to 50~55℃ before starting granulation; Granulation: The liquid material obtained in step ① is atomized by a nozzle and sprayed onto the powder in a fluidized state; The granulation conditions are as follows: atomization pressure 0.1~0.3MPa, turn on the spray gun for granulation, control the liquid supply rate 50~150rpm, and keep the liquid obtained in step ① in a stirring state during the granulation process; After granulation, the pellets are dried. ③ Whole grains; ④ Total Mixing: Add the granulated granules, corn starch, and talcum powder to the mixer in sequence, seal the container, mix, and discharge the mixture after mixing is complete. ⑤ Tableting: Tableting is performed using a tablet press, controlling the hardness of the raw tablets to be 4.5~8kg; ⑥ Coating: Add the remaining water from the prescription to the mixing tank, turn on the compressed air, and add the components of the film coating premix while stirring. After the addition is complete, continue stirring. Place the uncoated tablets in the coating pan and preheat to a tablet bed temperature of 40-50℃. Coat the tablets, controlling the tablet bed temperature at 35-55℃ during the coating process. Dry the tablets after coating. After drying, turn off the heating and wait until the tablet bed temperature is ≤35℃ before unloading the tablets. The formulation of the desloratadine tablets is as follows: Core ingredients: 5-6 parts by weight of desloratadine, 50-53 parts by weight of dicalcium phosphate dihydrate, 3-5 parts by weight of corn starch, 4-5 parts by weight of pregelatinized starch, 11-17 parts by weight of microcrystalline cellulose A, 10-14 parts by weight of microcrystalline cellulose B, 8-10 parts by weight of talc, 0-4 parts by weight of glycerin; Film coating premix: 1-1.5 parts by weight of hydroxypropyl methylcellulose, 1.5-2 parts by weight of lactose, 1-2 parts by weight of titanium dioxide, 0.7-1.7 parts by weight of polyethylene glycol 600, 0.3-1 parts by weight of colorant, and 0-4 parts by weight of glycerin.

3. The method for preparing desloratadine tablets according to claim 1 or claim 2, characterized in that, The formulation of the desloratadine tablets is as follows: Tablet core: 5 parts by weight of desloratadine, 53 parts by weight of dicalcium phosphate dihydrate, 3 parts by weight of corn starch, 4 parts by weight of pregelatinized starch, 13 parts by weight of microcrystalline cellulose A, 14 parts by weight of microcrystalline cellulose B, 8 parts by weight of talc, and 2 parts by weight of glycerin; Film coating premix: 1 part by weight hydroxypropyl methylcellulose, 1.5 parts by weight lactose, 1 part by weight titanium dioxide, 1.7 parts by weight polyethylene glycol 600, and 0.3 parts by weight colorant.

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