Calcium acetate raw material medicine with characteristic powder science and preparation method of preparation of calcium acetate raw material medicine
By adjusting the particle size of calcium acetate raw materials and the ratio of ethanol wetting agents, controlling the tap density of the total mixed particles, the problems of difficulty in filling existing calcium acetate preparations and large wear of equipment are solved, and the easy swallowing of calcium acetate capsules is achieved Improvement of performance and productivity.
Patent Information
- Application Number
- CN202411416392.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-11
- Publication Date
- 2024-12-20
AI Technical Summary
The wet particle tap density of existing calcium acetate preparations is too low, resulting in loose overall mixed particles, making it difficult to fill with small capsule shells, and the equipment is worn greatly, which affects the convenience of swallowing and production efficiency.
By adjusting the particle size distribution of calcium acetate raw materials and the ratio of ethanol wetting agent, controlling the wet mixing time and liquid addition amount, ensuring that the tap density of the total mixed particles is between 0.85-0.95, and stirring during dry mixing and wet mixing is used. Frequency and time, combined with drying and whole-particle steps, prepare easy-to-fille calcium acetate capsule preparations.
It realizes the swallowability and equipment protection of calcium acetate capsule preparation, meets the filling needs of smaller capsule shells, reduces equipment wear and improves production efficiency.
Smart Images
Figure CN119157901A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the technical field of pharmaceutical manufacturing, and in particular to a method for preparing a calcium acetate raw material drug having characteristic powder properties and a preparation thereof. Background Art
[0002] Calcium is one of the most important mineral nutrients in the human body. It is distributed in the blood, muscles, nerves, and bones throughout the body. People must take in enough calcium every day to ensure the stability of calcium concentration in the blood and maintain the normal physiological function of nerve cells. Capsules made of calcium acetate particles are mainly used to prevent and treat calcium deficiency diseases such as osteoporosis, tetany, bone dysplasia, rickets, and calcium supplementation for children, pregnant and lactating women, menopausal women, and the elderly.
[0003] When the relevant technology is used to make soft materials, it is found that the tap density of the prepared wet granules is between 0.58-0.66, and the tap density of the total mixed granules of the capsules after the whole granules are mixed is between 0.83-0.85. The powder of the tap density of the total mixed granules is loose as a whole, and the proportion of fine powder is large. Therefore, a larger capsule shell is required for filling to reach the labeled content of the calcium acetate preparation. The use of a larger capsule shell is not convenient for swallowing, and the use of a small capsule shell cannot reach the labeled content of the calcium acetate preparation, and the equipment will also be worn more.
[0004] Therefore, it is necessary to provide a method for preparing a calcium acetate preparation that is easy to swallow. Summary of the invention
[0005] In order to solve or partially solve the problems existing in the related art, the present application provides a method for preparing a calcium acetate API and a preparation thereof with characteristic powder science. The preparation method can make the tap density of the total mixed particles of the calcium acetate preparation range from 0.85 to 0.95, which can meet the need of using a smaller capsule shell in the capsule preparation process, making the prepared calcium acetate capsule preparation easier to swallow.
[0006] The present application provides a calcium acetate API with characteristic powder physics.
[0007] The cumulative particle size distribution of calcium acetate raw material is D10 of 8-19 μm, D50 of 28-44 μm, and D90 of 61-92 μm.
[0008] The bulk density of calcium acetate raw material is 0.32-0.35 g / ml, the angle of repose is 25°-40°, and the moisture content is 5%-6%.
[0009] A method for preparing a preparation,
[0010] The calcium acetate raw materials are dry-mixed, and after the dry-mixing is completed, an ethanol wetting agent is continuously added for wet-mixing to obtain wet granules;
[0011] The mass of calcium acetate raw material is 3.71 kg; the amount of ethanol wetting agent added is 1.55 kg, the ethanol wetting agent addition time is 190 seconds, and the wet mixing time is 500 seconds;
[0012] Or the mass of calcium acetate raw material is 3.71 kg; the amount of ethanol wetting agent added is 1.4 kg; the ethanol wetting agent addition time is 135 seconds, and the wet mixing time is 500 seconds;
[0013] Or the mass of calcium acetate raw material is 3.71 kg; the amount of ethanol wetting agent added is 1.35 kg; the ethanol wetting agent addition time is 190 seconds, and the wet mixing time is 500 seconds;
[0014] The calcium acetate bulk drug is the above-mentioned calcium acetate bulk drug.
[0015] Optionally, the dry mixing includes pelletizing and stirring at 35 Hz, and the dry mixing time is 70-90 s.
[0016] Optionally, the wet mixing has a stirring frequency of 35 Hz.
[0017] Optionally, the following steps are also included:
[0018] The wet granules are granulated, dried, and then granulated again, magnesium stearate is added for total mixing to obtain total mixed granules, and the total mixed granules are filled into capsules to obtain calcium acetate capsules.
[0019] Optionally, the drying temperature is 80°C and the drying time is 90-120 minutes.
[0020] Optional, drying time of 90 minutes.
[0021] Optionally, the tap density of the total mixed particles is 0.85-0.95.
[0022] The technical solution provided by this application may have the following beneficial effects:
[0023] In the present application, calcium acetate API with a cumulative particle size distribution of d(0.1) of 8-19 μm, d(0.5) of 28-44 μm, and d(0.9) of 61-92 μm is used as a raw material to prepare a calcium acetate preparation, and the ratio of the calcium acetate raw material to the amount of ethanol wetting agent added, the time of adding the ethanol wetting agent, and the wet mixing time are reasonably selected, so that the tap density of the prepared total mixed granules is 0.85-0.95, and the proportion of powder particles and fine powder in the tap density is balanced, the equipment wear is small in the subsequent granulation process, and the filling is convenient, which can meet the needs of using a smaller capsule shell in the capsule preparation process, so that the prepared calcium acetate capsule preparation is easier to swallow.
[0024] It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present application. BRIEF DESCRIPTION OF THE DRAWINGS
[0025] The above and other objects, features and advantages of the present application will become more apparent through a more detailed description of exemplary embodiments of the present application in conjunction with the accompanying drawings, wherein the same reference numerals generally represent the same components in the exemplary embodiments of the present application.
[0026] Figure 1 It is a schematic diagram of the preparation process of calcium acetate capsules shown in the present application. DETAILED DESCRIPTION
[0027] The embodiments of the present application will be described in more detail below with reference to the accompanying drawings. Although the embodiments of the present application are shown in the accompanying drawings, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments described herein. On the contrary, these embodiments are provided to make the present application more thorough and complete, and to fully convey the scope of the present application to those skilled in the art.
[0028] Example 1
[0029] A method for preparing calcium acetate capsules comprises the following steps:
[0030] 1) Granulation
[0031] The particle size distribution of calcium acetate API is as follows: API particle size cumulative distribution D10 is 16.824 μm; API particle size cumulative distribution D50 is 41.901 μm; API particle size cumulative distribution D90 is 89.851 μm;
[0032] The bulk density of the calcium acetate raw material is 0.32-0.35 g / ml; the angle of repose of the calcium acetate raw material is 25°-40°; the moisture content of the calcium acetate raw material is 5%-6%; and the hygroscopicity of the calcium acetate raw material is 2%-4%.
[0033] 3.71 kg (calculated as C4H6CaO4·H2O) of each calcium acetate raw material having the above-mentioned characteristic powder physics was placed in a rapid wet mixing granulator, stirring was turned on for dry mixing, granulation and stirring were set to 35 Hz, and the dry mixing time was 70 s; after the dry mixing was completed, the granulation and stirring frequency was maintained at 35 Hz, and 1.55 kg of ethanol wetting agent was continuously added for wet mixing, the ethanol concentration was 48%, and the ethanol wetting agent was controlled to be added within 190 s, and stirring was continued to 500 s (wet mixing time) to obtain wet granules.
[0034] 2) Wet granulation
[0035] The wet granules are sized by a swing granulator equipped with a 4.5 mm stainless steel sieve. During the operation, the tightness of the granules should be consistent. The sized wet granules are continuously sucked into the boiling dryer through the vacuum pipe.
[0036] 3) Drying
[0037] Turn on the boiling dry granulator, set the inlet air temperature to 80℃, preheat to the set temperature, turn off the heating, suck all the wet granules after granulation into the boiling dryer, turn on the heating power of the boiling dryer again for heating, record the initial inlet air temperature and material temperature, and record them every 30 minutes during the drying process, and dry for 90 minutes.
[0038] After drying, stop heating, take samples from the sampling port, and use a rapid moisture analyzer to determine that the moisture content should be less than 1.0%. Pull the material out of the fluidized bed and discharge it.
[0039] 4) Whole grain
[0040] After drying, the granules are sized using a swing granulator equipped with a 1.3mm stainless steel sieve plate. After granulation, the granules are collected in a plastic barrel lined with a clean plastic bag and the materials are properly labeled.
[0041] Particle moisture control method: Rapid moisture meter. The moisture content of the particle should be less than 1.0% when measured by a rapid moisture meter.
[0042] 5) Total Mixing
[0043] The granules and magnesium stearate after granulation in step 4) are put into a two-dimensional motion mixer, the equipment is started, and the mixture is mixed for 20 minutes to obtain the total mixed granules, and the tap density of the total mixed granules is 0.873. The total mixed granules are discharged and placed in a plastic barrel lined with a clean plastic bag, the plastic bag is tied tightly, and the barrel cover is covered.
[0044] 6) Capsule filling
[0045] Capsule filling can be carried out after the total mixed particles pass the inspection.
[0046] The moisture content was detected to be 0.86%, less than 1%, which improved the stability of the calcium acetate API. The tap density of the wet granules and the tap density of the total mixed granules were detected to be 0.758 and 0.932, respectively. The tap density of the total mixed granules reached the preset range of 0.85-0.95, which is conducive to capsule filling.
[0047] Example 2
[0048] The difference between Example 2 and Example 1 is that the particle size distribution of the calcium acetate bulk drug is: the cumulative distribution D10 of the bulk drug particle size is 16.786 μm; the cumulative distribution D50 of the bulk drug particle size is 43.431 μm; the cumulative distribution D90 of the bulk drug particle size is 91.131 μm; and other conditions remain unchanged.
[0049] The moisture content was tested to be 0.83%, less than 1%. The tap density of the wet particles and the tap density of the total mixed particles were tested to be 0.68 and 0.864, respectively. The tap density of the total mixed particles reached the preset range of 0.85-0.95, which is conducive to capsule filling.
[0050] Example 3
[0051] The difference between Example 3 and Example 1 is that the particle size distribution of the calcium acetate bulk drug is: the cumulative distribution D10 of the bulk drug particle size is 18.195 μm; the cumulative distribution D50 of the bulk drug particle size is 38.100 μm; the cumulative distribution D90 of the bulk drug particle size is 71.851 μm; and other conditions remain unchanged.
[0052] The moisture content was tested to be 0.77%, less than 1%. The tap density of the wet particles and the tap density of the total mixed particles were tested to be 0.68 and 0.871, respectively. The tap density of the total mixed particles reached the preset range of 0.85-0.95, which is conducive to capsule filling.
[0053] Example 4
[0054] The difference between Example 4 and Example 1 is that in Example 2, the amount of ethanol wetting agent added is 1.4 kg; the ethanol wetting agent addition time is 135 s, and the wet mixing time is 500 s; other conditions remain unchanged.
[0055] The moisture content was tested to be 0.79%, less than 1%. The tap density of the wet particles and the tap density of the total mixed particles were tested to be 0.68 and 0.873 respectively. The tap density of the total mixed particles reached the preset range of 0.85-0.95, which is conducive to capsule filling.
[0056] Example 5
[0057] The difference between Example 5 and Example 1 is that the amount of ethanol wetting agent added is 1.35 kg; the ethanol wetting agent addition time is 190 s, and the wet mixing time is 500 s; other conditions remain unchanged.
[0058] The moisture content was tested to be 0.88%, less than 1%. The tap density of the wet particles and the tap density of the total mixed particles were tested to be 0.68 and 0.856 respectively. The tap density of the total mixed particles reached the preset range of 0.85-0.95, which is conducive to capsule filling.
[0059] Comparative Example 1
[0060] The difference between Comparative Example 1 and Example 1 is that the amount of ethanol added is reduced from 1.55 Kg to 1.35 Kg, and the wet mixing time is extended from 500 s to 800 s.
[0061] The moisture content was detected to be 0.66%, less than 1%. The tap density of wet particles and the tap density of total mixed particles were detected to be 0.66 and 0.846, respectively. The tap density of total mixed particles did not reach the preset range of 0.85-0.95, which is conducive to capsule filling.
[0062] Comparative Example 2
[0063] The difference between Comparative Example 2 and Example 1 is that water is used as the wetting agent, the amount of ethanol added is reduced from 1.55 kg to 1.35 kg, the wet mixing time is reduced from 500 s to 300 s, and the drying time is increased from 90 minutes to 180 minutes.
[0064] The moisture content was detected to be 3.14%, which is greater than 1%. The tap density of the wet particles and the tap density of the total mixed particles were detected to be 0.61 and 0.658, respectively. The tap density of the total mixed particles did not reach the preset range of 0.85-0.95, which is conducive to capsule filling.
[0065] Comparative Example 3
[0066] The difference between Comparative Example 3 and Example 1 is that the ethanol concentration is 40%, and the amount of ethanol added is reduced from 1.55 Kg to 1.35 Kg.
[0067] The detected moisture content was 0.66%, less than 1%. The tap density of wet particles and the tap density of total mixed particles were 0.65 and 0.823, respectively. The tap density of total mixed particles did not reach the preset range of 0.85-0.95, which is conducive to capsule filling.
[0068] Comparative Example 4
[0069] The difference between Comparative Example 4 and Example 1 is that the ethanol concentration is 35%, the amount of ethanol added is reduced from 1.55 kg to 1.38 kg, the addition of the ethanol wetting agent is controlled to be completed within 130 seconds, and the drying time is 120 minutes.
[0070] The detected moisture content was 1.32%, which was greater than 1%. The tap density of wet particles and the tap density of total mixed particles were 0.68 and 0.856, respectively. Although the tap density of total mixed particles reached the preset range of 0.85-0.95, which was conducive to capsule filling, there was a serious phenomenon of wall sticking.
[0071] Comparative Example 5
[0072] The difference between Comparative Example 5 and Example 1 is that the particle size distribution of the calcium acetate bulk drug is: the cumulative distribution D10 of the bulk drug particle size is 8.632 μm; the cumulative distribution D50 of the bulk drug particle size is 19.708 μm; the cumulative distribution D90 of the bulk drug particle size is 42.508 μm; and other conditions remain unchanged.
[0073] The detected moisture content was 0.58%, less than 1%. The tap density of wet granules and the tap density of total mixed granules were 0.628 and 0.824, respectively. The tap density of total mixed granules did not reach the preset range of 0.85-0.95, which is conducive to capsule filling.
[0074] It can be seen from Comparative Examples 1 to 4 that the tap density of the total mixed particles using other wetting agents, ethanol addition amounts, wet mixing times and drying times cannot reach the preset range of 0.85-0.95, which is conducive to capsule filling. It can be seen that only when the mass of the calcium acetate raw material is 3.71Kg, the amount of ethanol wetting agent added is 1.55kg, the ethanol wetting agent addition time is 190s and the wet mixing time is 500s; or the mass of the calcium acetate raw material is 3.71Kg, the ethanol wetting agent addition amount is 1.4kg, the ethanol wetting agent addition time is 135s and the wet mixing time is 500s; or the mass of the calcium acetate raw material is 3.71Kg, the ethanol wetting agent addition amount is 1.35kg, the ethanol wetting agent addition time is 190s and the wet mixing time is 500s, the tap density of the total mixed particles can reach the preset range of 0.85-0.95, which is conducive to capsule filling.
[0075] It can be seen from Comparative Example 5 that the cumulative distribution D10 of the particle size of the calcium acetate raw material is 8.632 μm, the cumulative distribution D50 of the raw material particle size is 19.708 μm, and the cumulative distribution D90 of the raw material particle size is 42.508 μm. The tap density of the wet particles and the tap density of the total mixed particles are detected, which are 0.628 and 0.824, respectively. The tap density of the total mixed particles does not reach the preset range of 0.85-0.95, which is conducive to capsule filling. It can be seen that the cumulative distribution of the particle size of the calcium acetate raw material must satisfy D10 of 8-19 μm, D50 of 28-44 μm, and D90 of 61-92 μm to reach the preset range of 0.85-0.95, which is conducive to capsule filling.
[0076] The embodiments of the present application have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and changes will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or improvements to the technology in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.
Claims
1. A calcium acetate API with characteristic powder properties. It is characterized in that The calcium acetate bulk drug has a cumulative particle size distribution of D10 of 8-19 μm, D50 of 28-44 μm, and D90 of 61-92 μm.
2. The calcium acetate bulk drug according to claim 1, It is characterized in that The bulk density of the calcium acetate raw material is 0.32-0.35 g / ml, the angle of repose is 25°-40°, and the moisture content is 5%-6%.
3. A method for preparing a preparation, It is characterized in that The calcium acetate raw materials are dry-mixed, and after the dry-mixing is completed, an ethanol wetting agent is continuously added for wet-mixing to obtain wet granules; The mass of the calcium acetate raw material is 3.71 kg; the amount of the ethanol wetting agent added is 1.55 kg, the ethanol wetting agent addition time is 190 seconds, and the wet mixing time is 500 seconds; Or the mass of the calcium acetate raw material is 3.71 kg; the amount of the ethanol wetting agent added is 1.4 kg; the ethanol wetting agent addition time is 135 seconds, and the wet mixing time is 500 seconds; Or the mass of the calcium acetate raw material is 3.71 kg; the amount of the ethanol wetting agent added is 1.35 kg; the ethanol wetting agent addition time is 190 seconds, and the wet mixing time is 500 seconds; The calcium acetate bulk drug is the calcium acetate bulk drug described in claim 1.
4. The preparation method according to claim 3, It is characterized in that The dry mixing includes pelletizing and stirring at 35 Hz, and the dry mixing time is 70-90 s.
5. The preparation method according to claim 3, It is characterized in that The wet mixing has a stirring frequency of 35 Hz.
6. The preparation method according to claim 3, It is characterized in that The following steps are also included: The wet granules are granulated, dried, and then granulated again, magnesium stearate is added for total mixing to obtain total mixed granules, and the total mixed granules are filled into capsules to obtain calcium acetate capsules.
7. The preparation method according to claim 6, It is characterized in that The drying temperature is 80° C. and the drying time is 90-120 minutes.
8. The preparation method according to claim 7, It is characterized in that The drying time was 90 minutes.
9. The preparation method according to claim 6, It is characterized in that The tap density of the total mixed particles is 0.85-0.95.