One-step granulation molding process and its application

Abstract

This invention relates to a one-step granulation process and its application. The one-step granulation process includes pulping, granulation, and final mixing and packaging steps. In the pulping process, β-cyclodextrin or a mixture of β-cyclodextrin and corn starch is added to the drug extract as a pulping excipient. In the granulation process, a mixture of corn starch and silica is added as an excipient, and the granulation is carried out under mild conditions of 50-80°C via spray forming. Finally, the product is obtained by sieving through a vibrating screen, final mixing, and inner packaging. This one-step granulation process uses mild conditions for forming and granulating, avoiding problems such as particle agglomeration during the forming process. It also eliminates the need for large amounts of excipients to prevent easily sticky and clumping drug powder from adhering to the walls. Furthermore, the product prepared by adding a small amount of excipients does not exceed the standard required yield, meeting national standards.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a one-step granulation process and its application. Background Technology

[0002] Traditional Chinese medicine (TCM) granules are single-herb preparations made from TCM decoction pieces through extraction, separation, concentration, and granulation. They represent a new dosage form that can replace decoction pieces for clinical prescription dispensing. Currently, spray drying and dry granulation technologies are primarily used to produce granules. For some varieties, such as Morinda officinalis, charred hawthorn, Cornus officinalis, hawthorn, and Citrus medica, a large amount of excipients is needed during spray drying to prevent the powder from sticking to the drying walls and affecting production. However, adding too many excipients exceeds the standard production volume, resulting in products that do not meet national standards. These varieties typically have high sugar content, large extract yield, low granule softening point, and poor extract flowability, leading to problems such as sticking and clumping during spray drying. These types of traditional Chinese medicines have the following characteristics: high sugar solubility in water, resulting in a large amount of extract obtained from water extraction, i.e., high yield, large production volume, and limited room for excipient addition; high sugar content leads to a low softening point during the drying process of the extract. Taking Cornus officinalis as an example, without excipients, the softening point is approximately 60-70℃. When the drying temperature is higher than the softening point, the extract clumps together. During spray drying, the spray temperature is 165-195℃. Due to the high temperature, the material sticks together in the spray tower and cannot form powder, causing blockage of the spray tower. The spray-dried powder of these traditional Chinese medicines is highly hygroscopic. Even with conventional excipient addition, exposure to air will cause it to absorb moisture and clump within 5-10 minutes. These problems can lead to substandard product yield, equipment malfunction, and non-compliance with formulation granule standards. Based on the above characteristics, the best solution for producing Chinese herbal medicine granules with high sugar content using spray drying is to add a large amount of excipients to overcome the engineering problems of spray drying. Adding a large amount of excipients raises the softening point of the extract, allowing for smooth spray drying and also reducing the granules' moisture absorption. While this method solves the process problems, it seriously fails to meet the national standard for production quantity, and the product quality does not meet the national standard for formulated granules.

[0003] Currently, some one-step granulation processes have been developed in existing technologies. For example, Chinese patent CN107913317A discloses a method for preparing traditional Chinese medicine granules, which involves uniformly spreading a mixture of traditional Chinese medicine on the conveyor belt of a vacuum belt dryer for vacuum drying. However, the heating zone temperature of this vacuum dryer can reach 98-105℃, resulting in a very large amount of excipients required, making it difficult to industrialize. Furthermore, the obtained drug granules are unlikely to meet national standards. Chinese patent CN108434292A discloses a method for preparing a traditional Chinese medicine composition for preventing and treating menstrual disorders. This method involves adding dextrin or starch as a substrate to a one-step granulator and spraying a drug extract as a binder into the one-step granulator for one-step granulation. Although this method uses a lower granulation temperature, it does not specify the amount of excipients to be added, making quality control difficult.

[0004] Therefore, in summary, the existing one-step granulation method still cannot overcome the problem of adhesion of highly viscous traditional Chinese medicine extract components during the granulation process by adding a small amount of excipients. Summary of the Invention

[0005] To address the problems existing in the prior art, this invention provides a one-step granulation process and its application, which uses a small amount of auxiliary materials to obtain a finished product with uniform granules, and the product quality meets the requirements of national standards.

[0006] In a first aspect, the present invention provides a one-step granulation and molding process method, comprising the following steps:

[0007] S1, pulping

[0008] The pulping excipients are added to the drug extract for pulping;

[0009] S2, Granulation

[0010] The material after slurrying in step S1 is heated, stirred evenly, and kept warm. Then, auxiliary materials are added to obtain a mixture. The mixture is further sprayed and granulated. The auxiliary material is corn starch or a mixture of corn starch and silicon dioxide.

[0011] S3, General Mixing, Packaging

[0012] The granules formed in step S2 are sieved through a vibrating screen with an upper 14-mesh sieve and a lower 80-mesh sieve to obtain granules with uniform particle size. Then, magnesium stearate is added to the mixing tank and mixed at 8 r / min for 30 min. Finally, the granules are encapsulated.

[0013] Furthermore, the slurrying excipient in step S1 is β-cyclodextrin or a mixture of β-cyclodextrin and corn starch.

[0014] Furthermore, the relative density of the drug extract in step S1 is 1.18 to 1.22;

[0015] Furthermore, the solid content of the drug extract in step S1 is 30-60%;

[0016] Furthermore, the mass ratio of β-cyclodextrin, corn starch, and silicon dioxide in the mixture before spraying is 1:1 to 10:0.1 to 0.5;

[0017] Furthermore, the drug extract accounts for 50-90% of the total mass of the mixture before spraying.

[0018] Furthermore, the spray forming temperature in step S2 is controlled at 50–80°C;

[0019] Furthermore, the fan frequency in the spray forming process in step S2 is 15-50Hz;

[0020] Furthermore, the peristaltic pump speed in the spray forming process in step S2 is 6-35 r / min;

[0021] Furthermore, the atomization pressure of the spray forming process in step S2 is 0.35 to 0.4 MPa.

[0022] Secondly, the present invention provides a one-step granulation molding excipient, the excipient comprising β-cyclodextrin, corn starch, and silicon dioxide.

[0023] Furthermore, the mass ratio of β-cyclodextrin, corn starch or corn starch base material, and silicon dioxide is 1:4 to 7:0.1 to 0.5;

[0024] Furthermore, the excipients are mixed with the drug extract, and the mass ratio of the drug extract to the excipients is 1:0.1 to 1;

[0025] 11. Further, the solid content of the pharmaceutical extract is 30-60%.

[0026] Thirdly, the one-step granulation process described in this invention is applied in the preparation of pharmaceutical formulations, food, and health products;

[0027] Furthermore, the medicine includes, but is not limited to, traditional Chinese medicine and its extracts, chemical drugs and raw materials;

[0028] Furthermore, the drug dosage form includes, but is not limited to, granules, powders, tablets, etc.

[0029] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0030] (1) The present invention adopts a one-step granulation molding process, which overcomes the defect of powder sticking to the wall during the spray drying process of traditional Chinese medicine granulation in the prior art. Thus, a small amount of excipients can be used to obtain a finished product with uniform granules, and the product quality meets the requirements of national standards.

[0031] (2) The one-step granulation process of the present invention uses mild conditions for granulation, so that the drying temperature during the granulation process is lower than the softening point of the Chinese medicine components, which will not cause problems such as drug powder sticking or clumping, which is conducive to industrial production. Attached Figure Description

[0032] Figure 1 This is a flowchart of the one-step granulation and molding process of the present invention. Detailed Implementation

[0033] Unless otherwise specified, the experimental methods described in the following embodiments of the present invention are generally performed under conventional conditions or as recommended by the manufacturer. All commonly used chemical reagents used in the embodiments are commercially available products.

[0034] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to limit the invention.

[0035] The terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, apparatus, product, or device that includes a series of steps is not limited to the steps or modules listed, but may optionally include steps not listed, or may optionally include other steps inherent to such process, method, product, or device.

[0036] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments. It should be understood that these descriptions are merely exemplary and not intended to limit the scope of the invention. Furthermore, descriptions of well-known structures and technologies are omitted in the following description to avoid unnecessarily obscuring the concepts of the invention.

[0037] The following embodiments further describe the present invention, but these embodiments are not intended to limit the scope of protection of the present invention.

[0038] Example 1: One-step granulation process

[0039] The specific steps of the one-step granulation and molding process in this embodiment are as follows:

[0040] S1, pulping

[0041] 64g of β-cyclodextrin was added to 1kg of roasted hawthorn extract (solid content 44.41wt%) for pulping;

[0042] S2, Granulation

[0043] Add the slurry from step S1 to the hawthorn extract, heat to no more than 80°C, stir evenly, keep warm at 60°C, then add 290g corn starch and 13.57g silica to obtain a mixture. Then, the mixture is spray-formed into granules. During the spray-forming process, the temperature is controlled at 55±5°C, the initial set frequency is 15HZ, the peristaltic pump speed is 6r / min, and the atomization pressure is 0.35MPa (the fan frequency range is 15~50Hz, the peristaltic pump speed range is 6~35r / min, and the atomization pressure range is 0.35~0.4MPa, depending on the material conditions during production).

[0044] S3, General Mixing, Packaging

[0045] The granules formed in step S2 are sieved through a vibrating screen with an upper 14-mesh sieve and a lower 80-mesh sieve to obtain granules with uniform particle size. Then, 2.39g of magnesium stearate is added to the mixing tank and mixed at 8r / min for 30min. Finally, the granules are encapsulated.

[0046] The granulated hawthorn prepared using the above one-step granulation process showed no abnormal phenomena such as agglomeration during the granulation process, and all indicators such as particle size and moisture content of the material met the standard requirements.

[0047] Example 2: One-step granulation process

[0048] The specific steps of the one-step granulation and molding process in this embodiment are as follows:

[0049] S1, pulping

[0050] 42g of β-cyclodextrin was added to 1kg of bergamot extract (solid content 41.80wt%) for pulping;

[0051] S2, Granulation

[0052] Add the slurry from step S1 to the Buddha's Hand extract, heat to no more than 80°C, stir evenly, keep warm at 60°C, then add 260g of corn starch and 12.24g of silica to obtain a mixture. Then, spray the mixture into granules. During the spraying process, the temperature is controlled at 55±5°C, the initial set frequency is 15HZ, the peristaltic pump speed is 6r / min, and the atomization pressure is 0.35MPa (the fan frequency range is 15~50Hz, the peristaltic pump speed range is 6~35r / min, and the atomization pressure range is 0.4~0.35MPa, depending on the material conditions during production).

[0053] S3, General Mixing, Packaging

[0054] The granules formed in step S2 are sieved through a vibrating screen with an upper 14-mesh sieve and a lower 80-mesh sieve to obtain granules with uniform particle size. Then, 2.16g of magnesium stearate is added to the mixing tank and mixed at 8r / min for 30min. Finally, the granules are encapsulated.

[0055] The Buddha's Hand preparation made using the above one-step granulation process showed no abnormalities such as clumping, and all indicators such as particle size and moisture content of the material met the standard requirements.

[0056] Example 3: One-step granulation process

[0057] The specific steps of the one-step granulation and molding process in this embodiment are as follows:

[0058] S1, pulping

[0059] Add 35g of β-cyclodextrin and 35g of corn starch to 1kg of Saposhnikovia divaricata extract (solid content 46.97wt%) for slurry preparation;

[0060] S2, Granulation

[0061] Add the slurry from step S1 to the windproof impregnation paste, heat to no more than 80℃, stir evenly, keep warm at 60℃, then add 133g corn starch and 12.75g silica to obtain a mixture. Then, spray the mixture into granules. During the spraying process, the temperature is controlled at 55±5℃, the initial frequency is set to 15HZ, the peristaltic pump speed is 6r / min, and the atomization pressure is 0.35MPa (the fan frequency range is adjusted to 15~50Hz, the peristaltic pump speed range is 6~35r / min, and the atomization pressure range is 0.35~0.4MPa depending on the material conditions during production).

[0062] S3, General Mixing, Packaging

[0063] The granules formed in step S2 are sieved through a vibrating screen with an upper 14-mesh sieve and a lower 80-mesh sieve to obtain granules with uniform particle size. Then, 3.19g of magnesium stearate is added to the mixing tank and mixed at 8r / min for 30min. Finally, the granules are encapsulated.

[0064] The windproofing preparation made using the above one-step granulation process showed no abnormalities such as clumping, and all indicators such as particle size and moisture content of the material met the standard requirements.

[0065] Example 4: One-step granulation process

[0066] The specific steps of the one-step granulation and molding process in this embodiment are as follows:

[0067] S1, pulping

[0068] Add 49g of β-cyclodextrin and 49g of corn starch to 1kg of Morinda officinalis extract (solid content 48.81wt%) for slurry preparation;

[0069] S2, Granulation

[0070] The material after slurrying in step S1 is added to the Morinda officinalis extract, heated to no more than 80°C, stirred evenly, and kept at 60°C. Then, 294g of corn starch and 8.31g of silica are added to obtain a mixture. The mixture is then spray-formed into granules. During the spray-forming process, the temperature is controlled at 55±5°C, the initial frequency is set to 15HZ, the peristaltic pump speed is 6r / min, and the atomization pressure is 0.35MPa (the fan frequency range is adjusted to 15~50Hz, the peristaltic pump speed range is 6~35r / min, and the atomization pressure range is 0.35~0.4MPa depending on the material conditions during production).

[0071] S3, General Mixing, Packaging

[0072] The granules formed in step S2 are sieved through a vibrating screen with an upper 14-mesh sieve and a lower 80-mesh sieve to obtain granules with uniform particle size. Then, 1.67g of magnesium stearate is added to the mixing tank and mixed at 8r / min for 30min. Finally, the granules are encapsulated.

[0073] The Morinda officinalis preparation made using the above one-step granulation process showed no abnormalities such as clumping, and all indicators of the material, including particle size and moisture content, met the standard requirements.

[0074] Comparative Examples 1-4

[0075] The difference between Comparative Examples 1-4 and Example 1 is that the slurry additives and the amount of additives added in the one-step granulation molding process of Comparative Examples 1-4 are different, while the other steps are the same, as shown in Table 1.

[0076] Table 1

[0077]

[0078] The results of the drug particles prepared according to the molding process of Comparative Examples 1-4 above are as follows:

[0079] Granulation was carried out under the conditions of Comparative Example 1. After spraying 50g of material, the material agglomerated, making it impossible to continue spraying and granulation.

[0080] Granulation was carried out under the conditions of Comparative Example 2, consuming 300g of extract. During the granulation process, there were flocculent floating objects. Spraying continued until the pot collapsed, and it was impossible to continue spraying and granulation.

[0081] Granulation was carried out under the conditions of trial production 3, consuming 800g of extract, and more base material was required under the same conditions, exceeding the national standard requirement for production quantity;

[0082] Granulation was carried out under the conditions of trial production 4. Under the same conditions, less excipients could be used to gradually consume the extract (1000g). However, the material was damp during the granulation process, requiring frequent shutdowns for drying, which was not conducive to actual production.

[0083] Comparative Examples 6–9

[0084] The difference from Example 4 is that the amounts of β-cyclodextrin, corn starch, and silica added in the one-step granulation process of Comparative Examples 6-9 are different, while the other steps are the same, as shown in Table 2.

[0085] Table 2

[0086]

[0087] The results of drug particles prepared according to the molding process of Comparative Examples 6-9 are as follows:

[0088] Granulation was carried out under the conditions of Comparative Example 6, consuming 400g of extract. The resulting granules were relatively light but large in volume, exceeding the packaging size.

[0089] Granulation was carried out under the conditions of Comparative Example 7, but there was no bottom material, so granulation was not possible.

[0090] Granulation was carried out under the conditions of Comparative Example 8, consuming 800g of extract. The granules gradually became moist and required frequent drying, making continuous granulation impossible.

[0091] Granulation was carried out under the conditions of trial production 9, consuming 600g of extract. The granules gradually became damp and required frequent drying, making continuous granulation impossible.

[0092] Comparative Example 10

[0093] The difference from Example 1 is that the temperature during the spraying process is 45°C, while the other steps are the same.

[0094] Comparative Example 11

[0095] The difference from Example 1 is that the temperature during the spraying process is 85°C, while the other steps are the same.

[0096] Comparative Example 12

[0097] The difference from Example 1 is that the preparation process uses spray drying for dry granulation, and the specific steps are as follows:

[0098] 64g of β-cyclodextrin and 290g of corn starch were added to 1kg of roasted hawthorn extract (solid content 15.82wt%), and then spray-dried. The spray temperature was 185℃ at the inlet and 105℃ at the outlet. The extract powder was collected, and silica and magnesium stearate were added in proportion. Dry granulation was then performed to obtain the final product. (Severe adhesion to the walls occurred during the spraying process, which could not be removed by vibration; therefore, production was stopped.)

[0099] The results of the drug particles prepared according to the molding process of Comparative Examples 10-12 are as follows:

[0100] Granulation was carried out under the conditions of Comparative Example 10, consuming 100g of extract. The granulation temperature was too low, the material was too moist, and it could not be dried, resulting in the production pot collapsing.

[0101] Granulation was carried out under the conditions of Comparative Example 11, consuming 300g of extract. Due to the high temperature, the granules softened and clumped, making it impossible to boil and causing the pot to collapse.

[0102] Granulation was carried out under the conditions of trial production 12, consuming 600g of extract. Initially, spraying was normal, but as the production time increased, the extract powder adhered to the tower wall and could not fall off after vibration. The extract powder collector at the bottom of the tower and the outlet cyclone separator could not collect the extract powder.

[0103] It should be noted that the specific features, structures, materials or characteristics described in this specification can be combined in any way. For the sake of brevity, not all possible combinations of the various technical features in the above embodiments have been described. Without contradiction, those skilled in the art can combine and integrate the different embodiments and features described in this specification.

[0104] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A one-step granulation and molding process, characterized in that, The process includes the following steps: S1, pulping The pulping excipients are added to the drug extract for pulping; S2, Granulation The material after slurrying in step S1 is heated, stirred evenly, and kept warm. Then, auxiliary materials are added to obtain a mixture. The mixture is further sprayed and granulated. The auxiliary materials are a mixture of corn starch and silicon dioxide. S3, General Mixing, Packaging The granules formed in step S2 are sieved through a vibrating screen with an upper 14-mesh sieve and a lower 80-mesh sieve to obtain granules with uniform particle size. Then, magnesium stearate is added to the mixing tank and mixed at 8 r / min for 30 min. Finally, the granules are encapsulated. The mass ratio of β-cyclodextrin, corn starch, and silicon dioxide in the mixture before spraying is 1:4-7:0.1-0.5; During the spray forming process, the temperature is controlled at 50-80℃, the fan frequency is 15-50Hz, and the atomization pressure is 0.35-0.4Mpa. The drug extract is one of the following: hawthorn extract, citron extract, saposhnikovia extract, or morinda extract. When the drug extract is charred hawthorn extract, the pulping excipient in step S1 is 64g of β-cyclodextrin, the drug extract in step S1 is 1000g of charred hawthorn extract, and the solid content of the charred hawthorn extract is 44.41wt%; the excipients in step S2 are 290g of corn starch and 13.57g of silicon dioxide. If the drug extract is bergamot extract, the slurry excipient in step S1 is 42g of β-cyclodextrin, the drug extract in step S1 is 1000g of bergamot extract, and the solid content of the bergamot extract is 41.80wt%; the excipients in step S2 are 260g of corn starch and 12.24g of silicon dioxide. If the drug extract is Saposhnikovia divaricata extract, the slurry excipients in step S1 are 35g β-cyclodextrin and 35g corn starch, the drug extract in step S1 is 1000g Saposhnikovia divaricata extract, and the solid content of the Saposhnikovia divaricata extract is 46.97wt%; the excipients in step S2 are 133g corn starch and 12.75g silicon dioxide; If the drug extract is Morinda officinalis extract, the slurry excipients in step S1 are 49g β-cyclodextrin and 49g corn starch, the drug extract in step S1 is 1000g Morinda officinalis extract, the solid content of the Morinda officinalis extract is 48.81wt%, and the excipients in step S2 are 294g corn starch and 8.31g silicon dioxide.

2. The one-step granulation and molding process according to claim 1, characterized in that, During the spray molding process, the peristaltic pump speed is 6-35 r / min.

3. The application of the one-step granulation process according to any one of claims 1 to 2 in the preparation of pharmaceutical formulations.

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