Preparation method of polyethylene glycol 3350 electrolyte powder

Abstract

The invention provides a preparation method of polyethylene glycol 3350 electrolyte powder, and particularly relates to the field of medicines. The preparation method comprises the following steps: S1, crushing the saccharin sodium, and sieving with a 40-80-mesh sieve, wherein the D90 particle size of the saccharin sodium is 100-150 microns; s2, dissolving 3-5g of potassium chloride, 16-18g of sodium bicarbonate and 34-36g of sodium chloride into ethanol which is 1-5 times of the total mass of the potassium chloride, the sodium bicarbonate and the sodium chloride to obtain a solution; s3, 1300-1320g of polyethylene glycol 3350 is put into a boiling granulator, the boiling granulator is started, the air inlet frequency ranges from 10 Hz to 45 Hz, and the air inlet temperature ranges from 30 DEG C to 40 DEG C; s4, laterally spraying the solution in the step S2 into a boiling granulator for drying and fluidizing at the temperature of 40-50 DEG C and the rotating speed of a peristaltic pump of 25-35 revolutions per minute; s5, after the solution is completely sprayed, continuously fluidizing for 30-40 minutes, and discharging; and S6, discharging, sieving with a 75-85-mesh sieve, adding 0.8-1.2 g of saccharin sodium salt and 8-12 g of essence in the S1, mixing in a 5L mixer at the rotating speed of 15 rpm for 10-30 minutes, and thus obtaining the target product. The method can solve the problem of poor mixing uniformity of the polyethylene glycol 3350 electrolyte prepared by the existing preparation method.

Description

Technical Field

[0001] The present invention belongs to the field of medicine, and particularly relates to a preparation method of polyethylene glycol 3350 electrolyte powder Background Art

[0002] Polyethylene glycol 3350 electrolyte powder usually obtains a sample with qualified mixing uniformity by pulverizing and sieving each material and adopting the method of geometric dilution for mixing. However, due to the large density difference between each material and the large difference in the particle state of the pulverized materials, it is often very difficult to mix the materials evenly by direct mixing. In view of the deficiencies of the prior art, a method for improving the mixing uniformity of polyethylene glycol 3350 electrolyte powder is now needed Summary of the Invention

[0003] The purpose of the present invention is to provide a preparation method of polyethylene glycol 3350 electrolyte powder, so as to solve the problem of poor mixing uniformity of the polyethylene glycol 3350 electrolyte powder prepared by the existing preparation method

[0004] The present invention provides the following technical solutions

[0005] A preparation method of polyethylene glycol 3350 electrolyte powder, comprising the following steps

[0006] S1. Saccharin sodium is pulverized and sieved through a 40-80 mesh sieve, and the D90 particle size of saccharin sodium is 100 μm - 150 μm

[0007] S2. 3 - 5 g of potassium chloride, 16 - 18 g of sodium bicarbonate, and 34 - 36 g of sodium chloride are dissolved in ethanol with a total mass of potassium chloride, sodium bicarbonate, and sodium chloride of 1 - 5 times to obtain a solution

[0008] S3. 1300 - 1320 g of polyethylene glycol 3350 is put into a fluidized bed granulator, and the air inlet frequency of the fluidized bed granulator is turned on at 10 Hz - 45 Hz, and the air inlet temperature is 30 - 40 °C

[0009] S4. The solution of S2 is sprayed into the fluidized bed granulator for drying and fluidization from the side, and the rotational speed of the peristaltic pump is 25 - 35 revolutions per minute, and the temperature is 40 - 50 °C

[0010] S5: After all the solution is sprayed, continue fluidization for 30 - 40 minutes, and then discharge the material

[0011] S6: After discharging, sieve through a 75 - 85 mesh sieve, add 0.8 - 1.2 g of saccharin sodium and 8 - 12 g of essence in S1, use a 5 L mixer with a rotational speed of 15 rpm, and mix for 10 min - 30 min to obtain the target product

[0012] Preferably, in step S1, saccharin sodium is pulverized and sieved through a 60 mesh sieve, and the D90 particle size of saccharin sodium is 125 μm

[0013] Preferably, in step S2, 4.66 g of potassium chloride, 17.87 g of sodium bicarbonate and 35.07 g of sodium chloride are dissolved in 200 g of ethanol solution.

[0014] Preferably, in step S3, 1312.5 g of polyethylene glycol 3350 is placed in a fluidized bed granulator, and the air inlet of the fluidized bed granulator is turned on at 30 Hz with an air inlet temperature of 35 °C.

[0015] Preferably, in step S4, the solution of S2 is sprayed into the fluidized bed granulator for drying and fluidization, and the peristaltic pump rotates at a speed of 30 revolutions per minute, and the temperature is raised to 45 °C.

[0016] Preferably, in step S5, after all the solution is sprayed, fluidization is continued for 35 minutes and then discharged.

[0017] Preferably, in step S6, after the material is discharged, it is sieved through a 80-mesh sieve, 1 g of saccharin sodium and 10 g of essence are added, the mixer is 5 L, the rotation speed is 15 rpm, and mixing is carried out for 15 min.

[0018] Preferably, the essence is lemon essence or sweet orange essence or lime essence or a mixture of multiple flavors thereof.

[0019] Advantages of the present invention:

[0020] The present invention solves the problem of poor mixing uniformity of polyethylene glycol 3350 electrolyte powder prepared by the existing preparation method through the technology of dissolving inorganic salt components and re-granulating the main component polyethylene glycol 3350. Detailed implementation manners

[0021] Example 1:

[0022] A preparation method of polyethylene glycol 3350 electrolyte powder, comprising the following steps:

[0023] S1. Saccharin sodium is pulverized and sieved through a 40-mesh sieve, and the D90 particle size of saccharin sodium is 100 μm;

[0024] S2. 3 g of potassium chloride, 16 g of sodium bicarbonate and 34 g of sodium chloride are dissolved in 80 g of ethanol to obtain a solution;

[0025] S3. 1300 g of polyethylene glycol 3350 is placed in a fluidized bed granulator, and the air inlet frequency of the fluidized bed granulator is turned on at 10 Hz, and the air inlet temperature is 30 °C;

[0026] S4. The solution of S2 is sprayed into the fluidized bed granulator for drying and fluidization, and the peristaltic pump rotates at a speed of 255 revolutions per minute, and the temperature is 40 °C;

[0027] S5: After all the solution is sprayed, fluidization is continued for 30 minutes and then discharged;

[0028] S6: After discharging, pass through a 75-mesh sieve, add 0.8 g of sodium saccharin in S1, 8 g of essence, a 5-L mixer, rotate at 15 rpm, and mix for 10 min to obtain the target product.

[0029] Take 12 samples of the product prepared in Example 1, numbered 1a - 12a respectively, and the test data are as follows:

[0030] Sampling Number Sodium Bicarbonate Total Chlorine Content Potassium Chloride 1a 96.50％ 97.89％ 100.27％ 2a 100.11％ 100.31％ 101.08％ 3a 96.87％ 97.49％ 97.70％ 4a 103.87％ 104.01％ 101.67％ 5a 96.64％ 97.10％ 97.83％ 6a 98.45％ 99.07％ 99.11％ 7a 97.69％ 99.71％ 100.39％ 8a 98.15％ 100.69％ 97.36％ 9a 102.02％ 101.87％ 101.62％ 10a 97.95％ 100.46％ 100.45％ 11a 96.49％ 97.66％ 97.25％ 12a 96.50％ 97.89％ 100.27％ Mean 98.44％ 99.51％ 99.58％ RSD 2.43％ 2.09％ 1.67％

[0031] Example 2:

[0032] S1. Crush sodium saccharin and pass through a 60-mesh sieve. The D90 particle size of sodium saccharin is 125 μm.

[0033] S2. Dissolve 4.66 g of potassium chloride, 17.87 g of sodium bicarbonate, and 35.07 g of sodium chloride in 200 g of ethanol to obtain a solution.

[0034] S3. Put 1312.5 g of polyethylene glycol 3350 into a fluidized bed granulator, and turn on the inlet air frequency of the fluidized bed granulator at 30 Hz and the inlet air temperature at 35°C.

[0035] S4. Spray the solution of S2 into the fluidized bed granulator for drying and fluidization, with the peristaltic pump rotating at 25 - 35 revolutions per minute and the temperature at 40 - 50°C.

[0036] S5: After all the solution is sprayed, continue fluidizing for 35 minutes and then discharge.

[0037] S6: After discharging, pass through an 80-mesh sieve, add 1 g of sodium saccharin in S1, 10 g of essence, a 5-L mixer, rotate at 15 rpm, and mix for 15 min to obtain the target product.

[0038] Take 12 samples of the product prepared in Example 2, numbered 1b - 12b respectively, and the test data are as follows:

[0039] Sampling Number Sodium Bicarbonate Total Chlorine Content Potassium Chloride 1b 98.36％ 98.54％ 96.32％ 2b 96.79％ 98.36％ 96.39％ 3b 96.36％ 97.58％ 97.66％ 4b 96.31％ 97.25％ 98.55％ 5b 98.74％ 98.11％ 98.85％ 6b 97.31％ 97.82％ 98.33％ 7b 99.48％ 99.45％ 99.00％ 8b 98.81％ 98.38％ 97.58％ 9b 96.41％ 95.91％ 99.34％ 10b 99.50％ 100.77％ 96.33％ 11b 100.03％ 99.24％ 95.70％ 12b 98.52％ 99.87％ 94.34％ Mean 98.05％ 98.44％ 97.37％ RSD 1.38％ 1.31％ 1.59％

[0040] Example 3:

[0041] A preparation method of polyethylene glycol 3350 electrolyte powder, comprising the following steps:

[0042] S1. Crush sodium saccharin and pass through an 80-mesh sieve. The D90 particle size of sodium saccharin is 150 μm.

[0043] S2. Dissolve 5 g of potassium chloride, 18 g of sodium bicarbonate, and 36 g of sodium chloride in 280 g of ethanol to obtain a solution.

[0044] S3. Put 1320 g of polyethylene glycol 3350 into a fluidized bed granulator, and turn on the inlet air frequency of the fluidized bed granulator at 45 Hz and the inlet air temperature at 40°C.

[0045] S4. Spray the solution side of S2 into a fluidized bed granulator for drying and fluidization. The peristaltic pump rotates at 35 revolutions per minute and the temperature is 50 °C;

[0046] S5: After all the solution is sprayed, continue fluidizing for 40 minutes and then discharge the material;

[0047] S6: After discharging, pass through an 85-mesh sieve, add 1.2 g of saccharin sodium and 12 g of essence in S1, use a 5 L mixer, rotate at 15 rpm, and mix for 30 min to obtain the target product.

[0048] Take 12 samples of the product prepared in Example 3, numbered 1c - 12c respectively, and the test data are as follows:

[0049] Sampling Number Sodium Bicarbonate Total Chlorine Content Potassium Chloride 1c 99.89％ 96.05％ 102.26％ 2c 101.50％ 97.23％ 98.70％ 3c 99.87％ 99.22％ 99.84％ 4c 103.28％ 107.78％ 106.06％ 5c 101.34％ 101.11％ 99.86％ 6c 97.70％ 96.02％ 97.43％ 7c 108.41％ 96.49％ 96.70％ 8c 94.44％ 93.42％ 105.59％ 9c 98.51％ 94.23％ 102.19％ 10c 101.15％ 98.51％ 97.09％ 11c 100.71％ 97.72％ 93.63％ 12c 101.34％ 98.26％ 102.26％ Mean 100.68％ 98.00％ 100.13％ RSD 3.31％ 3.81％ 3.70％

[0050] Control group experiment: Conduct three groups of experiments, namely Control Group 1, Control Group 2, and Control Group 3, using existing traditional technologies; different comminution processes are used in Control Group 1 and Control Group 2, and different mixing processes are used in Control Group 1, Control Group 2, and Control Group 3. The specific details are as follows:

[0051] Control Group 1

[0052] Mixing 1: Add 4.66 g of potassium chloride, 17.85 g of sodium bicarbonate, 35.07 g of sodium chloride, and 1 g of saccharin sodium, mix and pass through a 60-mesh sieve, repeat three times.

[0053] Mixing 2: Add 112.5 g of polyethylene glycol 3350, use a 2 L mixer, mix for 30 min, rotate at 15 rpm.

[0054] Mixing 3: Add 200 g of polyethylene glycol 3350, use a 2 L mixer, mix for 30 min, rotate at 15 rpm.

[0055] Mixing 4: Add 300 g of polyethylene glycol 3350, use a 5 L mixer, mix for 30 min, rotate at 15 rpm.

[0056] Mixing 5: Add 700 g of polyethylene glycol 3350, use a 5 L mixer, mix for 30 min, rotate at 15 rpm to obtain the product.

[0057] Take 12 samples of the product prepared in Control Group 1, numbered 1d - 12d respectively, and the test data are as follows:

[0058] Sampling Number Sodium Bicarbonate Total Chlorine Content Potassium Chloride 1d 73.32％ 78.49％ 82.56％ 2d 105.23％ 109.75％ 104.28％ 3d 103.37％ 108.96％ 106.37％ 4d 93.61％ 95.87％ 98.28％ 5d 102.41％ 116.47％ 101.06％ 6d 103.53％ 105.79％ 102.23％ 7d 105.55％ 98.23％ 102.56％ 8d 93.57％ 96.92％ 102.63％ 9d 98.11％ 103.78％ 104.26％ 10d 99.88％ 106.50％ 107.78％ 11d 112.18％ 104.63％ 102.64％ 12d 107.36％ 109.76％ 106.37％ Mean 99.84％ 102.93％ 101.75％ RSD 9.96％ 9.46％ 6.46％

[0059] Control Group 2

[0060] Pretreatment: Crush sodium chloride through an 80-mesh sieve, crush potassium chloride through an 80-mesh sieve, crush sodium bicarbonate through a 60-mesh sieve, and crush saccharin sodium through a 60-mesh sieve.

[0061] Mixture 1: 4.66 g of potassium chloride, 17.85 g of sodium bicarbonate, 35.07 g of sodium chloride, and 1 g of sodium saccharin were added. After mixing, it was passed through a 60-mesh sieve and repeated twice.

[0062] Mixture 2: 60 g of polyethylene glycol 3350 was added. The mixer was 2 L, and the mixture was stirred for 15 min at a speed of 15 rpm.

[0063] Mixture 3: 120 g of polyethylene glycol 3350 was added. The mixer was 2 L, and the mixture was stirred for 15 min at a speed of 15 rpm.

[0064] Mixture 4: 232.5 g of polyethylene glycol 3350 was added. The mixer was 2 L, and the mixture was stirred for 15 min at a speed of 15 rpm.

[0065] Mixture 5: 500 g of polyethylene glycol 3350 was added. The mixer was 5 L, and the mixture was stirred for 15 min at a speed of 15 rpm. The mixing uniformity was sampled and tested.

[0066] Mixture 6: 400 g of polyethylene glycol 3350 was added. The mixer was 5 L, and the mixture was stirred for 15 min at a speed of 15 rpm. The mixing uniformity was sampled and tested.

[0067] Twelve samples were taken from the product prepared in Control Group 2 and numbered 1e - 12e respectively. Among them, the samples from step Mixture 5 were numbered 1e - 6e, and the samples from step Mixture 6 were numbered 7e - 12e. The test data are as follows:

[0068] Sampling Number Sodium Bicarbonate Total Chlorine Content Potassium Chloride 1e 102.77％ 102.34％ 102.63％ 2e 95.63％ 97.42％ 97.43％ 3e 94.47％ 91.91％ 97.37％ 4e 93.39％ 94.30％ 104.82％ 5e 113.57％ 115.73％ 112.02％ 6e 100.03％ 101.90％ 95.22％ 7e 106.47％ 109.01％ 94.53％ 8e 102.90％ 103.78％ 103.86％ 9e 87.71％ 88.74％ 86.72％ 10e 103.85％ 105.99％ 98.18％ 11e 104.46％ 106.74％ 102.75％ 12e 102.71％ 97.72％ 102.26％ Mean 100.66％ 101.30％ 99.82％ RSD 6.85％ 7.59％ 6.39％

[0069] Control Group 3

[0070] Pretreatment: Sodium chloride was crushed and passed through an 80-mesh sieve, potassium chloride was crushed and passed through an 80-mesh sieve, sodium bicarbonate was crushed and passed through a 60-mesh sieve, and sodium saccharin was crushed and passed through a 60-mesh sieve.

[0071] Mixture 1: 4.66 g of potassium chloride, 17.87 g of sodium bicarbonate, 35.07 g of sodium chloride, 1 g of sodium saccharin, and 60 g of polyethylene glycol 3350 were added. The mixer was 2 L, and the mixture was stirred at a speed of 15 rpm for 10 min.

[0072] Screening: Screening was carried out through a lifting granulator with a 1.0-mm screen.

[0073] Mixture 2: 120 g of polyethylene glycol 3350 was added. The mixer was 2 L, and the mixture was stirred at a speed of 15 rpm for 10 min.

[0074] Mixture 3: 232.5 g of polyethylene glycol 3350 was added. The mixer was 2 L, and the mixture was stirred at a speed of 15 rpm for 10 min.

[0075] Mixture 4: Add polyethylene glycol 3350: 500 g, mixer 5 L, rotation speed 15 rpm, mix for 10 min.

[0076] Mixture 5: Add polyethylene glycol 3350: 400 g, mixer 5 L, rotation speed 15 rpm, mix for 15 min to obtain the product

[0077] Take 12 samples of the product prepared in Control Group 3, numbered 1f - 12f respectively, and the test data are as follows:

[0078] Sampling Number Sodium Bicarbonate Total Chlorine Content Potassium Chloride 1f 102.48％ 97.99％ 102.34％ 2f 105.01％ 106.41％ 97.42％ 3f 98.60％ 101.62％ 91.91％ 4f 103.87％ 104.36％ 94.30％ 5f 110.34％ 113.39％ 115.73％ 6f 86.55％ 89.70％ 101.90％ 7f 94.18％ 95.11％ 109.01％ 8f 95.62％ 98.04％ 103.78％ 9f 89.17％ 92.42％ 88.74％ 10f 101.28％ 106.14％ 105.99％ 11f 101.19％ 105.83％ 106.74％ 12f 95.08％ 97.57％ 102.34％ Mean 98.61％ 100.71％ 101.68％ RSD 6.91％ 6.75％ 7.48％

[0079] It can be seen from the experimental results that in the control group, Control 1 - 3 all adopted the equal - increment mixing method. Although it can be seen through the comparison between Control 1 and Control 2 that the mixing uniformity can be optimized after the material is pulverized, the optimized mixing uniformity still has RSD > 5%. Examples 1 - 3 are the improved mixing schemes in the present invention. According to the test results of sodium bicarbonate, total chlorine content and potassium chloride in the prescription, it is found that Examples 1 - 3 can all achieve RSD ≤ 5% of the mixing uniformity. Based on the "Technical Guidelines for the Study of Mixing Uniformity and In - process Dosage Unit Uniformity of Chemical Oral Solid Preparations", the optimization direction of the present invention is successful and effective.

[0080] The above are only the preferred embodiments of the present invention and are not used to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, for those skilled in the art, they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent substitution on some of the technical features. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A preparation method of polyethylene glycol 3350 electrolyte powder, characterized in that, The steps are as follows: S1. Saccharin sodium is crushed and sieved through a 40 - 80 mesh sieve, and the D90 particle size of saccharin sodium is 100μm - 150μm; S2. 3 - 5g of potassium chloride, 16 - 18g of sodium bicarbonate, and 34 - 36g of sodium chloride are dissolved in ethanol with a total mass of potassium chloride, sodium bicarbonate, and sodium chloride being 1 - 5 times, to obtain a solution; S3. 1300 - 1320g of polyethylene glycol 3350 is put into a fluidized bed granulator, and the inlet air frequency of the fluidized bed granulator is turned on at 10Hz - 45Hz, and the inlet air temperature is 30 - 40°C; S4. The solution in S2 is sprayed laterally into the fluidized bed granulator for drying and fluidization, and the peristaltic pump rotates at a speed of 25 - 35 revolutions per minute, and the temperature is 40 - 50°C; S5: After all the solution is sprayed, continue fluidizing for 30 - 40 minutes and then discharge the material; S6: After discharging the material, sieve it through a 75 - 85 mesh sieve, add 0.8 - 1.2g of saccharin sodium in S1, 8 - 12g of essence, a 5L mixer, rotate at a speed of 15rpm, and mix for 10min - 30min to obtain the target product.

2. The preparation method of polyethylene glycol 3350 electrolyte powder according to claim 1, wherein: In step S1, saccharin sodium is crushed and sieved through a 60 - mesh sieve, and the D90 particle size of saccharin sodium is 125μm.

3. The preparation method of polyethylene glycol 3350 electrolyte powder according to claim 1, characterized in that: In step S2, 4.66g of potassium chloride plus 17.87g of sodium bicarbonate plus 35.07g of sodium chloride are dissolved in 200g of ethanol solution.

4. A preparation method of polyethylene glycol 3350 electrolyte powder according to claim 1, characterized in that: In step S3, 1312.5g of polyethylene glycol 3350 is put into the fluidized bed granulator, and the inlet air of the fluidized bed granulator is turned on at 30Hz, and the inlet air temperature is 35°C.

5. A preparation method of polyethylene glycol 3350 electrolyte powder according to claim 1, characterized in that: In step S4, the solution in S2 is sprayed laterally into the fluidized bed granulator for drying and fluidization, and the peristaltic pump rotates at a speed of 30 revolutions per minute, and the temperature is raised to 45°C.

6. A preparation method of polyethylene glycol 3350 electrolyte powder according to any one of claims 1, characterized in that: In step S5, after all the solution is sprayed, continue fluidizing for 35 minutes.

7. A preparation method of polyethylene glycol 3350 electrolyte powder according to any one of claims 1, characterized in that: In step S6, after the material is discharged, sieve it through an 80 - mesh sieve, add 1g of saccharin sodium, 10g of essence, a 5L mixer, rotate at a speed of 15rpm, and mix for 15min.

8. A preparation method of polyethylene glycol 3350 electrolyte powder, as claimed in claim 1, wherein: The essence is lemon essence or sweet orange essence or lime essence or a mixture of its multi - flavor essences.