Preparation method of lamiophlomis rotata composition dispersible tablet for improving compressibility of raw materials and disintegration of finished product

Abstract

The invention relates to the technical field of traditional Chinese medicine composition production processes, in particular to a preparation method of lamiophlomis rotata composition dispersible tablets capable of improving compressibility of raw materials and disintegration of finished products, which comprises the following steps: carrying out carbon dioxide supercritical extraction on lamiophlomis rotata, drying the extract, and crushing to obtain supercritical extraction medicine powder; mixing the supercritical extraction medicine powder, the pregelatinized starch, the microcrystalline cellulose, the polyvinylpolypyrrolidone and the sucralose according to the formula ratio; carrying out dry granulation, adding magnesium stearate, and mixing to obtain mixed powder to be pressed; and tabletting to obtain the lamiophlomis rotata dispersible tablet. A supercritical extraction process is adopted, so that the transfer rate of luteolin, total flavonoids and the like is increased, and the quality and curative effect of a finished product are further improved; the lamiophlomis rotata dry paste powder obtained by the process contains a small amount of impurities such as colloid, and is matched with other auxiliary materials to improve the flowability and compressibility of the material and improve the quality of a finished product; and the preparation method is green and environment-friendly, reduces the production cost, and has ideal popularization and application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of production technology of traditional Chinese medicine compositions, and in particular to a method for preparing a dispersible tablet of a composition of Lamiophlomis lappa with improved compressibility of raw materials and disintegration of finished products. Background Art

[0002] Duyiwei capsules and Duyiwei tablets are varieties included in the 2020 edition of the Chinese Pharmacopoeia. Their functions and indications are: promoting blood circulation and relieving pain, removing blood stasis and stopping bleeding. They are used for incision pain and bleeding after various surgical operations, traumatic fractures, sprains of tendons and bones, rheumatic pain, metrorrhagia, dysmenorrhea, gingival swelling and pain, and bleeding. Among them, the production process of Duyiwei dispersible tablets is: crush 1000g of Duyiwei, decoct it with water three times for 1 hour each time, combine the decoction, filter, concentrate the filtrate to an appropriate amount, dry it below 80°C, crush it, add an appropriate amount of starch, make granules, dry it, press it into 1000 tablets, and wrap it with film coating or sugar coating. The production process of Duyiwei capsules is: crush 1000g of Duyiwei, decoct it with water three times for 1 hour each time, combine the decoction, filter, concentrate the filtrate to an appropriate amount, dry it below 80°C, crush it, add an appropriate amount of starch, make granules, dry it, put it into capsules, and make 1000 tablets. In addition to the above two dosage forms, in order to increase the bioavailability of the drug, it can also be prepared into dispersible tablets and other dosage forms. Dispersible tablets refer to tablets that can quickly disintegrate and evenly disperse in water. Compared with solid preparations such as ordinary tablets and capsules, dispersible tablets have the characteristics of easy administration, rapid disintegration, fast absorption and high bioavailability. The production process of the dispersible tablets of Du Yiwei is as follows: 1000g of Du Yiwei is crushed, and water (10, 6, and 6 times) is added and decocted three times, each time for 1 hour, the decoction is combined, filtered, and the filtrate is concentrated to a relative density of 1.05-1.10 (70°C) and spray-dried into a dry extract, crushed, and added with 80g of microcrystalline cellulose, 150g of cross-linked methylcellulose sodium, 45g of low-substituted-HPC, 43g of sodium carboxymethyl starch, 2g of magnesium stearate, and stevioside in appropriate amounts for granulation, drying, whole grains, tableting, and making 1000 tablets.

[0003] The herbal material of Lamiophaga is rich in a large number of colloids, flavonoids, luteolin and Lamiophaga, etc. The existing process uses water decoction extraction, concentration and spray drying to obtain the dry paste powder of Lamiophaga extract, and then mixes it with auxiliary materials, wet granulation, boiling drying, total mixing, and tableting to prepare Lamiophaga dispersible tablets. First, using water decoction extraction, the transfer rate of some effective components in Lamiophaga medicinal materials is not ideal, which affects the full play of the efficacy. In addition, since a large amount of colloid in the medicinal material enters the dry paste powder, the total mixture of Lamiophaga dispersible tablets prepared by the preparation process has poor compressibility, long disintegration time, poor dispersion uniformity, and often leads to unqualified product quality. In addition, the original extraction process decocts and extracts 3 times, decompression concentration, ointment spray drying, and the preparation unit includes wet granulation and boiling drying. The energy consumption in the production process is very large, and the production cost is quite high, which is not conducive to improving the market competitiveness of the product. Summary of the invention

[0004] The present invention aims to provide a method for preparing a dispersible tablet of a Lamiaceae composition with improved compressibility of raw materials and disintegration of finished products, so as to solve the technical problems that the therapeutic effect, compressibility, disintegration time and dispersion uniformity of the Lamiaceae dispersible tablets obtained by the production process of the prior art are not ideal.

[0005] In order to achieve the above object, the present invention adopts the following technical scheme:

[0006] A method for preparing a dispersible tablet of a compound of Lamiaceae with improved raw material compressibility and finished product disintegration properties comprises the following steps:

[0007] S1: performing carbon dioxide supercritical extraction on Lamiophlomis odoratum, drying and crushing the extract to obtain supercritical extraction powder;

[0008] S2: Mix the supercritical extraction powder, pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose; then perform dry granulation, and then add magnesium stearate to the powder obtained by dry granulation to obtain mixed powder to be compressed; and obtain Du Yiwei dispersible tablets after tableting.

[0009] The technical solution also provides a dispersible tablet of Lamiophlomis ulmoides obtained by a preparation method of a dispersible tablet of a Lamiophlomis ulmoides composition having improved compressibility of raw materials and disintegration of finished products.

[0010] The principle and beneficial effects of this technical solution are:

[0011] This technical solution adopts the supercritical carbon dioxide extraction method, which greatly improves the extraction effect of the active ingredients. In addition, the extract obtained by supercritical extraction is used for tableting, which significantly improves the compressibility of the raw materials, the dispersion uniformity of the tablets and the solubility of the active ingredients, thereby comprehensively improving the quality of the finished product.

[0012] Furthermore, in S1, the parameters of supercritical carbon dioxide extraction are set as follows: extraction kettle temperature 40-45°C, pressure 20-30 MPa; flow rate 100-130 L / h; extraction time 2-3 hours.

[0013] Furthermore, in S1, the number of times of supercritical carbon dioxide extraction is 3 times, and the extraction object is the powder of the Chinese medicinal material Lamiophlomis that has been crushed and passed through a 20-30 mesh sieve.

[0014] Furthermore, in S2, pregelatinized starch, microcrystalline cellulose, crospovidone, sucralose and magnesium stearate are all sieved through 80-100 meshes.

[0015] Further, in S2, the parameters of dry granulation are set as follows: propulsion force 10.0-16.0 T, granulation screen 60-80 mesh.

[0016] Furthermore, in S2, the supercritical extraction powder, pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose are mixed for 5 to 10 minutes; and the magnesium stearate and the powder obtained by dry granulation are mixed for 5 to 10 minutes.

[0017] Furthermore, the formula of the dispersible tablets of the Radix Angelicae Pubescentis composition is, in parts by weight: 80-100 parts of Radix Angelicae Pubescentis, 130-160 parts of microcrystalline cellulose, 130-160 parts of pregelatinized starch, 20-30 parts of cross-linked polyvinylpyrrolidone, 0.8-1.2 parts of sucralose, and 4-6 parts of magnesium stearate.

[0018] Furthermore, the cross-linked polyvinylpyrrolidone model is CL-100, and the microcrystalline cellulose model is UF711.

[0019] The microcrystalline cellulose is selected from microcrystalline cellulose UF711, and the cross-linked polyvinylpyrrolidone is selected from cross-linked polyvinylpyrrolidone CL-100, which can ensure the ideal compressibility of the raw materials and the ideal dispersion uniformity and dissolution of the finished tablets.

[0020] This technical solution is the first to use the supercritical extraction product of Lamiophlomis to prepare Lamiophlomis dispersible tablets. How to ensure that the mixed powder to be compressed for tableting has good compressibility is the first problem encountered by the inventor. After a lot of attempts, it was found that the use of microcrystalline cellulose (model: UF711) and pregelatinized starch is very critical to ensure compressibility (whether there is a phenomenon of decapping, cracking, etc.), tablet hardness, tablet dispersion uniformity and dissolution of effective ingredients; the use of cross-linked polyvinylpyrrolidone CL-100 is very critical to ensure tablet dispersion uniformity and dissolution of effective ingredients.

[0021] Furthermore, the pre-compression pressure of the tablet press is 3-5 KN, the main pressure is 30-35 KN, and the hardness of the Lamiophlomis dispersible tablet is 5-8N.

[0022] The technical principle of this technical solution is:

[0023] The herbal material of Lamiophlomis is rich in a large number of effective ingredients such as colloids, flavonoids, luteolin and Lamiophlomis. The conventional means of the prior art are used to extract Lamiophlomis, and the transfer rate of some effective ingredients in the herbal material of Lamiophlomis is not ideal, which affects the full play of the efficacy. In addition, due to the presence of ingredients such as colloids, the compressibility of the total mixture is relatively poor, and the dissolution of the tablets is not ideal. The inventor has conducted a lot of research on the extraction method of Lamiophlomis, and found that the use of supercritical carbon dioxide extraction has a positive promoting effect on improving the content of effective ingredients, the compressibility of the raw materials to be pressed into tablets, and the dissolution and dispersion uniformity of the finished product, achieving three goals at one stroke.

[0024] In addition, in order to ensure the hardness, uniformity of dispersion, disintegration and solubility of the finished tablets, the tableting process conditions (pre-compression and pressure) need to be reasonably set. The additives mixed with the extract powder also need to have specific properties to ensure compressibility and disintegration and solubility of the finished product.

[0025] In summary, the beneficial effects of this technical solution are:

[0026] (1) The supercritical extraction process of the technical solution has high extraction efficiency, especially the transfer rate of luteolin and total flavonoids is significantly higher than that of water extraction, which can improve the quality and efficacy of the finished product.

[0027] (2) The dry paste powder extracted by the new process contains very little impurities such as colloids. The dispersible tablets made by combining with the auxiliary materials selected by this process have ideal compressibility, strong disintegration performance (dispersion disintegration), and the dispersion uniformity meets the requirements.

[0028] (3) The process uses supercritical extraction and the preparation stage does not require large-scale energy consumption. The preparation method is green and environmentally friendly, greatly improves production efficiency, and greatly reduces production costs. DETAILED DESCRIPTION

[0029] The present invention is further described in detail below in conjunction with the examples, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following examples and experimental examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used can be obtained from commercial channels. Unless otherwise specified, the technical means used in the following examples are conventional means well known to those skilled in the art.

[0030] Example 1

[0031] The formula of the dispersible tablets of the combination of Lamiophlomis ulmoides is (by weight): 80-100 parts of Lamiophlomis ulmoides slices, 130-160 parts of microcrystalline cellulose (model: UF711), 130-160 parts of pregelatinized starch, 20-30 parts of cross-linked polyvinylpyrrolidone (model: CL-100), 0.8-1.2 parts of sucralose, and 4-6 parts of magnesium stearate. The above raw materials all meet the standards recorded in Part IV of the Chinese Pharmacopoeia (2020).

[0032] The preparation process of the dispersible tablets of the Lamiaceae composite is as follows:

[0033] Preparation of S1 supercritical extraction powder: Take the slices of Lamiophlomis lappa, crush them through a 20-30 mesh sieve, extract the powder three times through supercritical extraction, and obtain a dry paste after dissociation of carbon dioxide. Crush the paste through an 80 mesh sieve to obtain supercritical extraction powder. The parameters of supercritical extraction are set as follows: extraction kettle temperature 40-45°C, pressure 20-30MPa; flow rate 100-130L / h; each extraction time 2-3 hours.

[0034] Preparation of S2 Lamiophlomis dispersible tablets: Take S1 supercritical extraction powder, formula amount of pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose and add them to a three-dimensional motion mixer, mix for 5 to 10 minutes, transfer to a dry granulator, make block flakes, then sieve the whole granules, add formula amount of magnesium stearate, motor frequency 50HZ, mix for 5 to 10 minutes, obtain the mixed powder to be pressed, then set the tablet press pre-pressing pressure 3 to 5KN, main pressure 30 to 35KN, under the above parameter conditions (pre-pressing pressure + main pressure, main pressure is the main influencing factor), the hardness of the tablet can be controlled at 5 to 8N. Lamiophlomis dispersible tablets (12mm shallow concave round punch, specification: 0.5g / tablet) are obtained by tableting. This technical solution uses a conventional dry granulation process, after mixing the drug and other auxiliary ingredients, the mixed powder is pressed into flakes, and finally crushed into particles to obtain the powder to be processed for subsequent processing.

[0035] Among them, the particle size of pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone, sucralose and magnesium stearate must meet the condition that the particle size passes through a 80-100 mesh sieve. During the dry granulation process, the parameters are set to a propulsion force of 10.0-16.0 T and a granulation sieve of 60-80 mesh.

[0036] Example 2

[0037] This embodiment refers to Example 1, and the specific formula is:

[0038] 80 parts of Lamiophlomis herb slices, 130 parts of microcrystalline cellulose UF711, 130 parts of pregelatinized starch, 20 parts of cross-linked polyvinylpyrrolidone CL-100, 0.8 parts of sucralose, and 4 parts of magnesium stearate.

[0039] The specific preparation process is as follows:

[0040] S1: The crude powder of Lamiophlomis lappa (passed through a 30-mesh sieve) was subjected to supercritical extraction three times at a temperature of 40 °C and a pressure of 20 MPa, each extraction lasting 3 h;

[0041] S2: Preparation of Lamiophlomis dispersible tablets: Take S1 supercritical extraction powder, formula amount of pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose and add them into a three-dimensional motion mixer with a motor frequency of 50 Hz. Mix for 10 minutes, transfer to a dry granulator to make block-like flakes, then sieve the whole granules, add the formula amount of magnesium stearate, motor frequency of 50 Hz, mix for 10 minutes to obtain the mixed powder to be compressed, then set the tablet press pre-compression pressure to 3 KN and the main pressure to 30 KN, and press to obtain Lamiophlomis dispersible tablets (12 mm shallow concave round punch, specification: 0.5 g / tablet), with a tablet hardness of 5N.

[0042] Among them, the particle size of pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone, sucralose and magnesium stearate must meet the condition that the particle size passes through a 100-mesh sieve. During the dry granulation process, the parameters are set to a propulsion force of 12.0 T and a granulation sieve of 80 mesh.

[0043] Example 3

[0044] This embodiment is basically the same as Embodiment 2, except that, in S1, the crude powder of the medicinal material is subjected to supercritical extraction three times at a temperature of 40° C. and a pressure of 25 MPa, with each extraction lasting 2 hours.

[0045] Preparation of S2 Du Yiwei dispersible tablets: Take S1 supercritical extraction powder, formula amount of pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose, add them into a three-dimensional motion mixer, motor frequency 50HZ, mix for 10 minutes, transfer to a dry granulator, make block-like flakes, then sieve the whole grains, add the formula amount of magnesium stearate, motor frequency 50HZ, mix for 10 minutes to obtain the mixed powder to be compressed, then set the tablet press pre-compression pressure to 5KN and the main pressure to 35KN, and press to obtain Du Yiwei dispersible tablets (12mm shallow concave round punch, specification: 0.5g / tablet), the tablet hardness is 8N.

[0046] Example 4

[0047] This embodiment is basically the same as Embodiment 2, except that, in S1, the crude powder of the medicinal material is subjected to supercritical extraction three times at a temperature of 40° C. and a pressure of 30 MPa, with each extraction lasting 2 hours.

[0048] Preparation of S2 Du Yiwei dispersible tablets: Take S1 supercritical extraction powder, formula amount of pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose, add them into a three-dimensional motion mixer, motor frequency 50HZ, mix for 10 minutes, transfer to a dry granulator, make block-like flakes, then sieve the whole grains, add the formula amount of magnesium stearate, motor frequency 50HZ, mix for 10 minutes to obtain the mixed powder to be compressed, then set the tablet press pre-compression pressure to 5KN and the main pressure to 30KN, and press to obtain Du Yiwei dispersible tablets (12mm shallow concave round punch, specification: 0.5g / tablet), the tablet hardness is 5N.

[0049] Example 5

[0050] This embodiment is basically the same as Embodiment 2, except that, in S1, the crude powder of the medicinal material is subjected to supercritical extraction three times at a temperature of 45° C. and a pressure of 20 MPa, with each extraction lasting 2 hours.

[0051] Preparation of S2 Du Yiwei dispersible tablets: Take S1 supercritical extraction powder, formula amount of pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose and add them into a three-dimensional motion mixer with a motor frequency of 50HZ. Mix for 5 minutes, transfer to a dry granulator to make block-like flakes, then sieve the whole particles, add the formula amount of magnesium stearate, motor frequency of 50HZ, mix for 10 minutes to obtain the mixed powder to be compressed, then set the tablet press pre-compression pressure to 5KN and the main pressure to 33KN, and press to obtain Du Yiwei dispersible tablets (12mm shallow concave round punch, specification: 0.5g / tablet), with a tablet hardness of 6N.

[0052] Example 6

[0053] This embodiment is basically the same as Embodiment 2, except that, in S1, the crude powder of the medicinal material is subjected to supercritical extraction three times at a temperature of 45° C. and a pressure of 30 MPa, with each extraction lasting 2 hours.

[0054] Preparation of S2 Du Yiwei dispersible tablets: Take S1 supercritical extraction powder, formula amount of pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose, add them into a three-dimensional motion mixer, motor frequency 50HZ, mix for 8 minutes, transfer to a dry granulator, make block-like flakes, then sieve the whole grains, add the formula amount of magnesium stearate, motor frequency 50HZ, mix for 8 minutes to obtain the mixed powder to be compressed, then set the tablet press pre-compression pressure 4KN, the main pressure 35KN, and press to obtain Du Yiwei dispersible tablets (12mm shallow concave round punch, specification: 0.5g / tablet), the tablet hardness is 8N.

[0055] Comparative Example 1

[0056] This comparative example is basically the same as Example 2, except that the crude powder of the medicinal material is subjected to supercritical extraction three times at a temperature of 35°C and a pressure of 18 MPa, each extraction being 3 hours. The extraction temperature and pressure in this comparative example are relatively low, resulting in insufficient extraction of total flavonoids and luteolin and other effective components in the herb, so the content of effective components in the finished tablet is relatively low.

[0057] Comparative Example 2

[0058] This comparative example is basically the same as Example 2, except that the crude powder of the medicinal material is subjected to supercritical extraction three times at a temperature of 35°C and a pressure of 40MPa, each time for 3 hours. The extraction temperature in this comparative example is relatively low. Although the extraction pressure is increased, the total flavonoids and luteolin in the herb are still not fully extracted, so the content of the active ingredients in the finished tablet is relatively low.

[0059] Comparative Example 3

[0060] This comparative example is basically the same as Example 2, except that the crude powder of the medicinal material is subjected to supercritical extraction three times at a temperature of 50°C and a pressure of 15 MPa, each time for 3 hours. The extraction pressure in this comparative example is relatively low. Although the extraction temperature is increased, the total flavonoids and luteolin in the herb are still not fully extracted, so the content of the active ingredients in the finished tablets is relatively low.

[0061] Comparative Example 4

[0062] This comparative example is basically the same as Example 2, except that the crude powder of the medicinal material is subjected to supercritical extraction three times at a temperature of 50°C and a pressure of 40MPa, each time for 3 hours. Increasing the extraction temperature and pressure does not significantly increase the content of total flavonoids and luteolin and other effective ingredients in the finished product. From the perspective of energy conservation, it is not advisable to use a supercritical extraction method with too high a temperature and pressure.

[0063] Comparative Example 5

[0064] This comparative example was carried out with reference to the preparation method of conventional Lamiophlomis dispersible tablets in the prior art, as follows:

[0065] According to the formula of Example 2, take the herb of Radix Angelicae Pubescentis and grind it, add water (10, 6, 6 times) and boil it three times, each time for 1 hour, combine the decoction, filter, concentrate the filtrate to a clear paste with a relative density of 1.05-1.10 (70°C), reduce the pressure and dry it into a dry extract (water content ≦8%), and grind it. The dry extract powder and the formula amount of microcrystalline cellulose UK711, pregelatinized starch, cross-linked polyvinylpyrrolidone (CL-100) and sucralose are added to a three-dimensional motion mixer, mixed for 10 minutes, transferred to a dry granulator, made into block flakes, and then the whole grains are sieved (the dry granulation method is the same as in Example 2), and the formula amount of magnesium stearate is added, mixed for 10 minutes to form a mixed powder to be compressed, and then tableted to obtain the herb of Radix Angelicae Pubescentis dispersible tablets (the tableting method is the same as in Example 2). This comparative example uses the water decoction method to extract the herb of Radix Angelicae Pubescentis. Since the water decoction extraction has a limited effect on the extraction of the effective components, the content of total flavonoids and luteolin in the finished tablets is much lower than that in Example 2. In addition, the dry extract powder obtained by decoction and extraction has unsatisfactory compressibility in the subsequent tableting process, and the tablets may fall off and crack, and the surface finish of the tablets is poor, and the hardness of the obtained tablets is difficult to improve. In addition, due to the change in the extraction method, the dissolution and dispersion uniformity of the finished tablets are also significantly negatively affected. Moreover, the dispersion uniformity of the tablets prepared according to this scheme is not ideal.

[0066] Comparative Example 6

[0067] This comparative example refers to comparative example 5, and the extraction solvent is changed from water to 70% ethanol solution, as follows:

[0068] Take the Radix Angelicae Pubescentis and grind it, add 70% ethanol solution (10, 6, 6 times) and reflux extract three times, each time for 1 hour, combine the reflux extracts, filter, recover ethanol from the filtrate and concentrate it to a relative density of 1.05-1.10 (70°C), reduce the pressure and dry it into a dry extract, and grind it. Add the dry extract powder and the formula amount of microcrystalline cellulose UK711, pregelatinized starch, cross-linked polyvinylpyrrolidone (CL-100) and sucralose into a three-dimensional motion mixer to make block flakes, then sieve the whole grain (dry granulation method is the same as Example 2), add the formula amount of magnesium stearate, mix for 5-10 minutes, form a mixed powder to be pressed, and then press it into tablets to obtain the Radix Angelicae Pubescentis dispersible tablets (the tableting method is the same as Example 2). Using ethanol solution as the extraction solvent of Radix Angelicae Pubescentis also has similar situations as in Comparative Example 5.

[0069] Comparative Example 7

[0070] This comparative example is basically the same as Example 2, except that: during tableting, the pre-compression pressure of the tablet press is set to 2KN, the main pressure is set to 25KN, and the hardness of the obtained tablets is 4N. When the mixed powder to be compressed obtained by the method of this scheme is tableted, if the pressure is too low, the hardness of the tablets will be unsatisfactory.

[0071] Comparative Example 8

[0072] This comparative example is basically the same as Example 2, except that: during tableting, the pre-compression pressure of the tablet press is set to 5 KN, the main pressure is 40 KN, and the hardness of the obtained tablets is 10 N. When the mixed powder to be compressed obtained by the method of this scheme is tableted, if the pressure is too high, the hardness of the tablets will be too large, affecting the dispersion uniformity of the tablets.

[0073] Comparative Example 9

[0074] This comparative example is basically the same as Example 2, except that during tableting, the tablet press machine does not start pre-compression, and direct tableting is adopted. Not using the pre-compression method will lead to large-scale cracking of the finished product.

[0075] Comparative Example 10

[0076] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is changed to microcrystalline cellulose PH101.

[0077] Comparative Example 11

[0078] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is replaced by microcrystalline cellulose PH102.

[0079] Comparative Example 12

[0080] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is replaced with microcrystalline cellulose PH103.

[0081] Comparative Example 13

[0082] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is changed to microcrystalline cellulose PH105.

[0083] Comparative Example 14

[0084] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is changed to microcrystalline cellulose PH112.

[0085] Comparative Example 15

[0086] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is changed to microcrystalline cellulose PH113.

[0087] Comparative Example 16

[0088] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is changed to microcrystalline cellulose PH200NF.

[0089] Comparative Example 17

[0090] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is changed to microcrystalline cellulose PH301NF.

[0091] Comparative Example 18

[0092] This comparative example is basically the same as Example 2, except that microcrystalline cellulose UF711 is changed to microcrystalline cellulose PH302NF.

[0093] Comparative Example 19

[0094] This comparative example is basically the same as Example 2, except that corn starch replaces pregelatinized starch.

[0095] Comparative Example 20

[0096] This comparative example is basically the same as Example 2, except that cross-linked carboxymethyl cellulose sodium replaces cross-linked polyvinylpyrrolidone.

[0097] Comparative Example 21

[0098] This comparative example is basically the same as Example 2, except that low-substituted hydroxypropyl cellulose (L-HPC) replaces crospovidone.

[0099] Comparative Example 22

[0100] This comparative example is basically the same as Example 2, except that crospovidone CL-10 replaces crospovidone CL-100.

[0101] Comparative Example 23

[0102] This comparative example is basically the same as Example 2, except that a wet granulation method is adopted in step S2. The specific process is as follows: supercritical extraction powder of S1, formula amount of pregelatinized starch, microcrystalline cellulose UK711, half amount of cross-linked polyvinylpyrrolidone CL-100, and sucralose are added into a three-dimensional motion mixer and mixed for 10 minutes. Then, granulation is performed by wet method with 75% ethanol, dried, sieved through an 80-mesh sieve, half amount of cross-linked polyvinylpyrrolidone CL-100 and magnesium stearate are added, and the mixture is mixed for 20 minutes to obtain the mixed powder to be compressed, and then tableting is performed to obtain Du Yiwei dispersible tablets.

[0103] Experimental example

[0104] (1) Dispersion uniformity test method: Check according to the disintegration time limit test method (General Rule 0921), the inner diameter of the stainless steel mesh is 710μm, the water temperature is 15-25℃; take 6 tablets of the test product, all of which should disintegrate and pass through the sieve within 3 minutes. If a small amount cannot pass through the sieve, but has softened into a light weight and floats on the surface without a hard core, it meets the requirements. Dispersion uniformity test is used to evaluate the uniformity of drug dispersion in water. For dispersible tablets that need to be dispersed in water before taking, unsatisfactory dispersion uniformity will affect the compliance of the drug when taken.

[0105] (2) Identification, dissolution, total flavonoids and luteolin content are all tested with reference to the National Drug Registration Standard for Duyiwei Dispersible Tablets (YBZ06902009). Dissolution refers to the degree to which a drug dissolves from a solid preparation such as a tablet in a specified solvent. In the present technical scheme, the dissolution test is carried out in a conventional dissolution test device, with water as the dissolution medium, a rotation speed of 50 rpm, and a sample is taken after processing for 30 minutes. The percentage of total flavonoids of the effective ingredient obtained by quantitative analysis is the percentage of the effective ingredient dissolved in the original tablet. For each embodiment and comparative example, 6 tablets were used for dissolution test, and the experimental results in Table 1 are the average values ​​of 6 tablets. For each embodiment and comparative example, the total flavonoids and luteolin content tests were repeated 3 times, and the experimental results in Table 1 are the average values ​​of the three repetitions.

[0106] (3) Compressibility evaluation: mainly examines whether the tablets crack, fall off the cover, and tablet hardness during the tablet pressing process.

[0107] Table 1: Finished product test results

[0108]

[0109]

[0110]

[0111] Example 2-6 adopts the preparation method of this scheme to obtain the raw material of the dispersible tablet of Lamiophlomis lappa with good compressibility; after being pressed into tablets, the dispersion uniformity meets the requirements and the solubility can reach more than 85%; the content of the effective ingredients total flavonoids and luteolin in the tablets is relatively high, which improves the quality of the medicine.

[0112] In the process flow of the present technical solution, the use of supercritical extraction has a very critical impact on the compressibility of the raw materials and the quality of the medicine. Comparative Examples 5 and 6 respectively extract the effective ingredients from the medicinal material of Lamiophlomis lappa by water decoction extraction and ethanol extraction. When these extracts were used to prepare Lamiophlomis lappa dispersible tablets, it was found that the total flavonoids and luteolin content of the finished tablets were much different from those in Example 2. In addition, using the extraction methods of Comparative Examples 5 and 6, the compressibility of the raw materials was not ideal, and the phenomena of capping and flakes often occurred; and the dispersion uniformity and dissolution of the tablets were not ideal. This shows that the use of a specific extraction method (carbon dioxide supercritical extraction) to treat the medicinal material of Lamiophlomis lappa has a positive promoting effect on improving the content of effective ingredients, the compressibility of the raw materials to be pressed, and the dissolution and dispersion uniformity of the finished product.

[0113] In addition, the conditions of supercritical extraction (temperature and pressure) will also affect the content of total flavonoids and luteolin in the finished tablets (see Comparative Examples 1-4). Therefore, setting the temperature of supercritical extraction to 40-45°C and the pressure to 20-30MPa can ensure the content level of the functional substances in the product and at the same time ensure energy conservation.

[0114] When tabletting, whether to choose to use the pre-pressing step and the pressure setting of the tablet press will affect the appearance and performance of the tablets. The tableting pressure of Comparative Example 7 is too small, and the hardness of the finished product obtained is low and the surface is not smooth. The tableting pressure of Comparative Example 8 is too large, and the hardness of the finished product obtained is large, which also affects the dispersion uniformity of the tablets. Although excessive tableting pressure makes it difficult to achieve uniform dispersion of the skeleton components of the tablets, the smaller molecular functional components such as total flavonoids dispersed in the skeleton components can be dissolved better. Comparative Example 9 did not adopt the pre-pressing process, resulting in large-scale tablet fragmentation, so the inventor did not conduct subsequent performance tests on it.

[0115] In terms of auxiliary agents, microcrystalline cellulose must be selected from microcrystalline cellulose UF711 to ensure that the compressibility of the raw material is ideal, and the dispersion uniformity and dissolution of the finished tablets are ideal. The inventor has tried different types of microcrystalline cellulose in comparative examples 10-18 and found that if microcrystalline cellulose UF711 is not used, the compressibility of the raw material will be significantly reduced, the hardness of the tablets will be unsatisfactory, and the dispersion uniformity and dissolution of the tablets will be difficult to improve.

[0116] In the dispersible tablets of this scheme, microcrystalline cellulose UF711 has the triple function of improving the compressibility of the powder to be compressed, and improving the dispersion uniformity of the tablets and the dissolution rate of the effective ingredients. Improving the compressibility can ensure that tablets with suitable hardness are obtained under a certain pressure, and there will be no cracking or detachment. After the finished tablets are placed in water, microcrystalline cellulose has a certain water-conducting effect, and combined with the appropriate internal pressure of the tablets (mainly affected by the hardness of the tablets), it can promote the disintegration of the tablets in water. Due to the differences in the particle size of different types of microcrystalline cellulose, there are differences in the water-conducting effects of these microcrystalline celluloses, so the use of different microcrystalline celluloses leads to certain differences in the disintegration performance of the tablets, the degree of dispersion uniformity and the degree of dissolution of the effective ingredients. The microcrystalline cellulose UF711 of this scheme has significant advantages over other microcrystalline celluloses in the above-mentioned effects, which was not expected by the inventor before the experiment.

[0117] In terms of auxiliary agents, the selection of pregelatinized starch is also critical. If it is replaced with ordinary corn starch (Comparative Example 19), the compressibility of the raw material will be significantly reduced, and the dispersion uniformity and dissolution of the tablets are not ideal. The use of microcrystalline cellulose UF-711 makes the raw material easier to compress and form, but pregelatinized starch is required to be used in combination with microcrystalline cellulose UF-711 to ensure that the effect of microcrystalline cellulose UF-711 is fully exerted. In addition to the above-mentioned corn starch and pregelatinized starch, the inventors also tried wheat starch, wheat starch, pea starch, cassava starch, pregelatinized hydroxypropyl starch, etc. (in accordance with the standards recorded in the four parts of the Chinese Pharmacopoeia) during the exploration process, and found that the compressibility of the mixed powder to be compressed prepared using the above-mentioned auxiliary materials was not ideal. Under the condition of equal replacement with pregelatinized starch (other conditions are the same as Example 2), the compressibility evaluation result is similar to that of Comparative Example 19, the dispersion uniformity test is unqualified, and the dissolution is between 73-78%. This shows that microcrystalline cellulose UF-711 needs to be used in combination with pregelatinized starch to ensure ideal drug performance.

[0118] In terms of adjuvants, the selection of cross-linked polyvinylpyrrolidone CL-100 is more important. In comparative examples 20-22, the inventors tried other types or other models of disintegrants. Compared with Example 2, under the same tableting method, the hardness of the tablets increased, and the uniformity of tablet dispersion was not ideal, and the dissolution rate was poor. This shows that microcrystalline cellulose UF-711 needs to be used in conjunction with cross-linked polyvinylpyrrolidone CL-100 in this solution to ensure the uniformity of dispersion and the dissolution rate of the effective ingredients.

[0119] In terms of granulation method, dry granulation has a more significant promoting effect on improving the uniformity of tablet dispersion, disintegration performance, uniformity of dispersion and dissolution rate compared with wet granulation (Comparative Example 23).

[0120] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions and / or characteristics in the solution is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several modifications and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A method for preparing a dispersible tablet of a compound of the same herb that improves the compressibility of the raw materials and the disintegration of the finished product, It is characterized in that The following steps are involved: S1: performing carbon dioxide supercritical extraction on Lamiophlomis odoratum, drying and crushing the extract to obtain supercritical extraction powder; S2: Mix the supercritical extraction powder, pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose; then perform dry granulation, and then add magnesium stearate to the powder obtained by dry granulation to obtain mixed powder to be compressed; and obtain Du Yiwei dispersible tablets after tableting.

2. A method for preparing a dispersible tablet of a compound of Lamiaceae with improved raw material compressibility and finished product disintegration according to claim 1, It is characterized in that In S1, the parameters of supercritical carbon dioxide extraction are set as follows: extraction kettle temperature 40-45°C, pressure 20-30MPa; flow rate 100-130L / h; extraction time 2-3 hours.

3. A method for preparing a dispersible tablet of a compound of Lamiophlomis odorifera having improved compressibility of raw materials and disintegration of finished products according to claim 2, It is characterized in that In S1, the number of times of carbon dioxide supercritical extraction is 3 times, and the extraction object is the powder of Lamiophlomis lappa that has been crushed and passed through a 20-30 mesh sieve.

4. A method for preparing a dispersible tablet of a compound of Lamiaceae with improved raw material compressibility and finished product disintegration according to claim 1, It is characterized in that In S2, pregelatinized starch, microcrystalline cellulose, crospovidone, sucralose and magnesium stearate were all sieved through 80-100 meshes.

5. A method for preparing a dispersible tablet of a composition of Lamiophlomis odorifera with improved compressibility of raw materials and disintegration of finished products according to claim 4, It is characterized in that In S2, the parameters of dry granulation are set as follows: propulsion force 10.0-16.0 T, granulation screen 60-80 mesh.

6. A method for preparing a dispersible tablet of a composition of Lamiophlomis lappa with improved compressibility of raw materials and disintegration of finished products according to claim 5, It is characterized in that In S2, the supercritical extraction powder, pregelatinized starch, microcrystalline cellulose, cross-linked polyvinylpyrrolidone and sucralose are mixed for 5 to 10 minutes; and the magnesium stearate and the powder obtained by dry granulation are mixed for 5 to 10 minutes.

7. A method for preparing a dispersible tablet of a compound of Lamiophlomis odorifera having improved compressibility of raw materials and disintegration of finished products according to claim 1, It is characterized in that The formula of the dispersible tablets of the Radix Angelicae Pubescentis composition is as follows, in parts by weight: 80-100 parts of Radix Angelicae Pubescentis, 130-160 parts of microcrystalline cellulose, 130-160 parts of pregelatinized starch, 20-30 parts of cross-linked polyvinylpyrrolidone, 0.8-1.2 parts of sucralose, and 4-6 parts of magnesium stearate.

8. A method for preparing a dispersible tablet of a compound of Lamiophlomis odorifera having improved compressibility of raw materials and disintegration of finished products according to claim 1, It is characterized in that The microcrystalline cellulose model is UF711, and the cross-linked polyvinylpyrrolidone model is CL-100.

9. A method for preparing a dispersible tablet of a compound of Lamiophlomis odorifera having improved compressibility of raw materials and disintegration of finished products according to claim 1, It is characterized in that In S2, the pre-compression pressure of the tablet press is 3-5 KN, the main pressure is 30-35 KN, and the hardness of the Lamiophlomis dispersible tablet is 5-8N.

10. A dispersible tablet of Lamiophlomis lappa prepared by the method for preparing a dispersible tablet of a Lamiophlomis lappa composition with improved compressibility of raw materials and disintegration of finished products according to any one of claims 1 to 8.

Images