Sailuotong orally disintegrating tablet and preparation method thereof

Abstract

The present invention relates to a SLT orodisintegrating tablet and a preparation method thereof, and belongs to the technical field of SLT orodisintegrating tablets. The SLT orodisintegrating tablet comprises the following raw materials: 10 parts by weight of ginseng, 8 parts by weight of ginkgo leaves, 0.18 parts by weight of saffron, 0.15-0.25 parts by weight of a proppant, and 0.02-0.04 parts by weight of an adhesive. The preparation method of the SLT orodisintegrating tablet comprises the following two steps: S1, taking ginseng extract, ginkgo leaf extract, saffron extract, a proppant, and an adhesive, fully mixing them, and concentrating them under reduced pressure to a relative density of 1.12-1.14 at 70°C to obtain a concentrated paste; S2, freeze-drying the concentrated paste to obtain a SLT orodisintegrating tablet. The SLT orodisintegrating tablets prepared by the present invention are uniform in color, full and smooth, without cracked edges or flakes, and also have a good disintegration effect.

Description

Technical Field

[0001] The invention relates to the preparation of a SLT orodisintegrating tablet, in particular to a SLT orodisintegrating tablet and a preparation method thereof. Background Art

[0002] Freeze-dried SLT orodisintegrating tablets refer to a new dosage form prepared by freeze-drying a specially formulated solution. Compared with SLT orodisintegrating tablets prepared by traditional tablet compression, it has the characteristics of high porosity, rapid disintegration, less excipients, and high bioavailability. When taken, it can be quickly disintegrated in the mouth only through saliva, without the need for water. Its active ingredients can be directly and quickly absorbed through the oral mucosa to avoid the first-pass effect of the liver. It is particularly suitable for the elderly, children, patients with mental illnesses, and patients with dysphagia, and can greatly improve the medication compliance of these people.

[0003] The eutectic point and eutectic point are important parameters in the vacuum freeze-drying process of freeze-dried SLT orally disintegrating tablets, and are of great significance for determining the pre-freezing temperature and sublimation temperature. The eutectic point refers to the temperature at which the water in the material is completely frozen into ice crystals, and the eutectic point refers to the temperature at which the ice crystals of the completely frozen material begin to melt during the heating process.

[0004] In the freeze-drying process, too high a sublimation temperature or too fast a heating speed will cause the tablet to collapse. If the sublimation temperature is too low, the water evaporates very slowly, resulting in very small pores. The temperature rise will easily cause the fragile and tiny skeleton to collapse. Slow heating is conducive to maintaining its skeleton structure, but the energy consumption increases, resulting in an overall longer disintegration time and lumps, and a messy and irregular microstructure. Summary of the invention

[0005] The technical problem to be solved by the present invention is that when the existing preparation process of Seluotong orodisintegrating tablets is used to prepare Seluotong orodisintegrating tablets, a traditional Chinese medicine composition containing ginseng, ginkgo leaves and saffron, the tablet formation rate is low and the quality of Seluotong orodisintegrating tablets is poor.

[0006] In order to achieve the above-mentioned object, the present invention provides a SLT orodisintegrating tablet, the raw materials of which include: 10 parts by weight of ginseng, 8 parts by weight of ginkgo leaves, 0.18 parts by weight of saffron, 0.15-0.25 parts by weight of a proppant and 0.02-0.04 parts by weight of a binder.

[0007] Preferably, the proppant is D-mannitol; and the binder is sucrose.

[0008] The present invention also provides a method for preparing a SLT orally disintegrating tablet, comprising the following steps:

[0009] S1, taking ginseng extract, ginkgo leaf extract, saffron extract, proppant and adhesive, fully mixing and concentrating under reduced pressure to a relative density of 1.12 to 1.14 at 70° C., to prepare a concentrated paste;

[0010] S2, freeze-drying the concentrated paste to prepare Sailuotong orodisintegrating tablets;

[0011] The freeze drying comprises pre-freezing, primary drying, secondary drying and re-drying which are performed in sequence.

[0012] Preferably, in step S2, the pre-freezing vacuum degree is 10 Pa and the temperature is -45°C.

[0013] Preferably, in step S2, the vacuum degree of primary drying is 10 Pa and the temperature is -34 to -30°C.

[0014] Preferably, in step S2, the vacuum degree of the secondary drying is 10 Pa and the temperature is -24 to -20°C.

[0015] Preferably, the vacuum degree of re-drying is 10 Pa and the temperature is 23°C.

[0016] Preferably, in step S1, the method for preparing the ginseng extract comprises the following steps:

[0017] A. Grind 10 parts by weight of ginseng into powder, add ethanol and reflux extract twice, filter, and

[0018] The solvent is recovered by decompressing the liquid to obtain an extract with a relative density of 1.12 to 1.14 at 70°C;

[0019] B. Add the extract to 2 to 6 times the weight of ginseng in water, stir evenly, cool and precipitate, and apply the obtained supernatant to macroporous adsorption resin. The macroporous adsorption resin is first rinsed with distilled water and then eluted with ethanol. The ethanol eluate is collected to obtain the ginseng extract.

[0020] Preferably, in step S1, the method for preparing the ginkgo leaf extract comprises the following steps:

[0021] a. Grind 8 parts by weight of ginkgo leaves into coarse powder, add warm ethanol to soak, filter, add warm ethanol to soak the residue again, filter, combine the two leaching solutions, and concentrate under reduced pressure to a relative density of 1.02 to 1.04 at 70°C;

[0022] b. Extract with a mixture of ethyl acetate and n-butanol, combine the extracts, and recover the solvent under reduced pressure.

[0023] Ginkgo leaf extract was obtained.

[0024] Preferably, in step S1, the method for preparing the saffron extract comprises the following steps:

[0025] ①, take 0.18 weight parts of saffron, add ethanol to soak, filter, add ethanol to soak again,

[0026] Filter, combine the two leaching solutions, and concentrate under reduced pressure until the relative density is 1.12-1.14 at 70°C;

[0027] ②. Add water and apply macroporous adsorption resin. Rinse the macroporous adsorption resin with distilled water and then with ethanol column. Collect the ethanol eluate to obtain saffron extract.

[0028] The beneficial effects achieved by the present invention are:

[0029] 1. The relative density of the concentrated paste in step S1 is 1.12-1.14. The SLT orally disintegrating tablets prepared at this relative density have excellent appearance and fast disintegration speed.

[0030] 2. The primary drying temperature in the freeze-drying process is lower than the eutectic temperature, thereby appropriately reducing the speed of water sublimation, preventing tablet collapse, and forming channels of appropriate size and a stable skeleton structure inside the tablet. The temperature is maintained for a long time to allow the water in the tablet to fully sublimate, preventing the phenomenon of melting tablets during the second drying.

[0031] 3. The secondary drying temperature in the freeze-drying process is higher than the turning point of the eutectic curve, and the evaporation rate of water becomes faster. Since the appropriate amount of water has been removed from the Seloton disintegrating tablets during the first drying process, a stable pore and skeleton structure has been formed inside the tablets. At this time, the rapid evaporation of water will not cause the tablets to collapse or melt, shortening the cooling time and saving energy. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 The eutectic point curve diagram of the concentrated paste of the Chinese medicine composition of the present invention measured by the electrical resistance method;

[0033] Figure 2 The figure is a eutectic point curve of the concentrated paste of the Chinese medicine composition of the present invention measured by the electrical resistance method. DETAILED DESCRIPTION

[0034] The technical solutions in the embodiments of the present invention are described clearly and completely below in conjunction with the embodiments of the present invention. In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention can also be implemented in other ways different from those described herein, and those skilled in the art can make similar generalizations without violating the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed below.

[0035] I. The preparation method of the Chinese medicine composition Sailuotong orodisintegrating tablets described in the present invention is as follows:

[0036] 1. Extraction of crude drugs

[0037] 1. Preparation of ginseng extract

[0038] A. Grind 10 kg of ginseng into powder, extract twice with ethanol reflux, filter, and recover the solvent from the filtrate under reduced pressure until the relative density is 1.12-1.14 at 70°C;

[0039] B. Add 2 to 6 times the weight of ginseng in water and stir evenly. Cool and precipitate. Add macroporous adsorption resin to the supernatant. Rinse the drug-loaded resin with distilled water first, then elute with ethanol. Collect the ethanol eluate to obtain ginseng extract.

[0040] 2. Preparation of Ginkgo Extract

[0041] a. Grind 8 kg of ginkgo leaves into coarse powder, soak in warm ethanol, filter, soak the residue in warm ethanol again, filter, combine the two leaching solutions, and concentrate under reduced pressure to a relative density of 1.02 to 1.04 at 70°C;

[0042] b. Extract with a mixture of ethyl acetate and n-butanol, combine the extracts, and recover the solvent under reduced pressure to obtain a ginkgo leaf extract.

[0043] 3. Preparation of saffron extract

[0044] ①, take 0.18kg of saffron, add ethanol to cold soak, filter, add ethanol to cold soak the residue again, filter, combine the two leaching solutions, and concentrate under reduced pressure to a relative density of 1.12-1.14 at 70℃;

[0045] ②. Add water and apply macroporous adsorption resin. Rinse the drug-loaded resin with distilled water and then with ethanol column. Collect the ethanol eluate to obtain saffron extract.

[0046] 2. Preparation of SLT Oral Disintegrating Tablets

[0047] S1. Mix the ginseng extract, ginkgo leaf extract and saffron extract obtained by the above method, add 0.15-0.25 kg of D-mannitol and 0.02-0.04 kg of sucrose to the extract of the obtained Chinese medicine composition, sonicate until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12-1.14 at 70°C to obtain a concentrated paste;

[0048] S2, placing the concentrated cream prepared by the above method into a mold, pre-freezing at -45°C in a freeze-drying device with a vacuum degree maintained at 10 Pa for 1 hour;

[0049] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and primary drying is performed at -34 to -30°C;

[0050] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -24 to -20°C;

[0051] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the mixture is dried at 35° C. to obtain the Selotong orally disintegrating tablets.

[0052] II. Quality evaluation method of freeze-dried Sailuotong orodisintegrating tablets:

[0053] The quality inspection of freeze-dried Sailuotong orodisintegrating tablets is divided into qualified and unqualified, with qualified scoring 1 point and unqualified scoring 0 point. The specific quality inspection contents are as follows:

[0054] 1. Appearance inspection

[0055] Color: Take out the tablets and observe them under bright light. Tablets with uniform color and lustre are qualified. Tablets with halos or boundaries are unqualified.

[0056] Appearance: Take out the tablets and observe them under bright light. Tablets that are round, plump and smooth are qualified. Tablets with pitting, cracks or depressions on the surface are unqualified.

[0057] Cracked edge: Take out the tablets and observe them in a brightly lit place. Tablets without cracked edges or splits are qualified; tablets with cracks on the surface are unqualified.

[0058] Tablet melting: Take out the tablet, turn it upside down, break it apart, and observe it in a brightly lit place. If the tablet is melted at the bottom but not in the center, it is qualified; if the tablet is melted, it is unqualified.

[0059] Sticking tablets: Take out the tablets, turn them upside down, break them apart, and observe them in a brightly lit place. If the area where the tablets stick to the packaging material is less than 10% (including 10%) of the total area of ​​the tablets, it is qualified; if it exceeds 10%, it is unqualified.

[0060] 2. Disintegration Time Limit

[0061] According to the requirements of the disintegration time limit test method for Seluotong orodisintegrating tablets in the 2020 edition of the Chinese Pharmacopoeia, the disintegration time limit is determined using a Seluotong orodisintegrating tablet disintegration instrument. The specific method is as follows:

[0062] Instrument device: The main structure is a lifting bracket and a stainless steel pipe with a screen at the bottom. The lifting bracket moves up and down 10mm±1mm, and the reciprocating frequency is 30 times per minute.

[0063] Fix the stainless steel tube on the bracket and immerse it in a 1000ml cup containing about 900ml of water at a temperature of 37℃±1℃. Adjust the water level so that the screen is 15mm±1mm below the water surface when the stainless steel tube is at the lowest position. Start the instrument. Take a tablet of Seloton disintegrating tablet and put it in the above stainless steel tube for inspection. If it completely disintegrates within 12 seconds (including 12 seconds) and passes through the screen, it is qualified; if the disintegration time is greater than 12 seconds, it is unqualified.

[0064] 3. Weight Difference

[0065] According to the provisions of the 2020 edition of the "Chinese Pharmacopoeia", the weight difference is checked as follows.

[0066] Take 20 tablets of the test sample, accurately weigh the total weight, and after obtaining the average tablet weight, accurately weigh each tablet separately, and compare the weight of each tablet with the average tablet weight (for tablets without content determination or Chinese medicine tablets with labeled tablet weight, the weight of each tablet should be compared with the labeled tablet weight). According to the provisions in the table, no more than 2 tablets shall exceed the weight difference limit, and no one tablet shall exceed the limit by 1 times. The weight difference limit for average tablet weight or labeled tablet weight below 0.3g is ±7.5%.

[0067] Tablet weight difference calculation formula: Tablet weight difference (%) = (single tablet weight - average tablet weight) / average tablet weight × 100%.

[0068] 4. Hardness

[0069] Six tablets of SALOTONG disintegrating tablets were randomly selected from each group (all the six tablets were relatively complete tablets without obvious cracks / fragments or melting). The hardness of the tablets was measured using a tablet hardness tester (test range: 2-199.9N), that is, the magnitude of the force displayed on the instrument when pressure was applied in the radial direction of the tablet to break the tablet into two halves.

[0070] III. Screening of freeze-drying process

[0071] 1. Determination of eutectic point

[0072] The eutectic point and eutectic point of the concentrated paste obtained in step S1 are measured by the resistance method. The resistance value of the prescription solution is measured with the eutectic point tester to obtain the change of the temperature, and a resistance-temperature scatter plot is drawn, such as Figure 1 As shown in the figure, when the temperature starts to drop to -18℃, the resistance value starts to increase. When the temperature drops to -38℃, the resistance value reaches the maximum. Therefore, the eutectic point temperature of the concentrated paste is determined to be -38℃. After continuing to cool down for a period of time, the temperature starts to rise. Figure 2 As shown, when the temperature rises to -27°C, the resistance value continues to decrease, and -27°C is the eutectic point temperature of the concentrated paste.

[0073] 2. Determination of the dosage of excipients and freezing temperature for SLT orodisintegrating tablets

[0074] 1. Determination of the dosage of D-mannitol

[0075] In order to eliminate the influence of other factors, this part of the embodiments follows the single factor variable principle, and the specific embodiments are as follows.

[0076] Example 1

[0077] S1. Add 0.10 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until the extract is completely dissolved, and concentrate under reduced pressure to a relative density of 1.13 at 70° C. to obtain a concentrated paste;

[0078] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0079] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0080] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0081] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0082] Example 2

[0083] S1. Add 0.15 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.13 at 70° C. to obtain a concentrated paste;

[0084] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0085] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0086] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0087] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0088] Example 3

[0089] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.13 at 70° C. to obtain a concentrated paste;

[0090] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0091] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0092] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0093] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0094] Example 4

[0095] S1. Add 0.25 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, sonicate until completely dissolved, and concentrate under reduced pressure to a relative density of 1.13 at 70° C. to obtain a concentrated paste;

[0096] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0097] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0098] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0099] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0100] Example 1 is marked as Group 1; Example 2 is marked as Group 2; Example 3 is marked as Group 3; Example 4 is marked as Group 4. The freeze-dried SLT orodisintegrating tablets quality evaluation method recorded in the second aspect of the present invention were used to score the SLT orodisintegrating tablets. For each evaluation, 10 SLT orodisintegrating tablets were randomly selected from each group, and the total scores were calculated by group. A qualified score was 1 point, and a failed score was 0 point. The scoring results are shown in Table 1.

[0101] Table 1

[0102]

[0103] In the above embodiment, when the dosage of D-mannitol is 0.10kg, the SLT orodisintegrating tablets are prone to cracking, splitting, pitting and cracking on the surface, and depression of the tablets; when the dosage of D-mannitol exceeds 0.20kg, the disintegration rate of the SLT orodisintegrating tablets decreases slightly. Based on the above analysis, the optimal dosage of D-mannitol is about 0.15-0.25kg.

[0104] 20 tablets were randomly selected from each of Groups 1 to 4 for weight difference evaluation. The evaluation results are shown in Table 2.

[0105] Table 2

[0106]

[0107] When the dosage of D-mannitol was 0.01kg, the SLT orodisintegrating tablets showed fragmentation and splitting, resulting in an average tablet weight much lower than the average tablet weight of other groups; when the dosage of D-mannitol was 0.15-0.25kg, the SLT orodisintegrating tablets could maintain a good average tablet weight and keep a low number of over-limits.

[0108] The hardness of Group 1 to Group 4 was evaluated, and the evaluation results are shown in Table 3.

[0109] Table 3

[0110]

[0111] When the dosage of D-mannitol is 0.01kg, the hardness of the Sailuotong orodisintegrating tablets is low, and therefore more cracked edges and split tablets occur; when the dosage of D-mannitol is 0.15-0.25kg, the hardness of different tablets is not much different, which is suitable for industrial production.

[0112] 2. Determination of sucrose dosage

[0113] In order to eliminate the influence of other factors, this part of the embodiments follows the single factor variable principle, and the specific embodiments are as follows.

[0114] Example 5

[0115] S1. Add 0.20 kg of D-mannitol and 0.01 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until the extract is completely dissolved, and concentrate under reduced pressure to a relative density of 1.13 at 70° C. to obtain a concentrated paste;

[0116] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0117] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0118] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0119] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0120] Example 6

[0121] S1. Add 0.20 kg of D-mannitol and 0.02 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until the extract is completely dissolved, and concentrate under reduced pressure to a relative density of 1.13 at 70° C. to obtain a concentrated paste;

[0122] S2, placing the concentrated cream prepared by the above method into a mold, pre-freezing at -45°C in a freeze-drying device with a vacuum degree maintained at 10 Pa for 1 hour;

[0123] S3, the vacuum degree of the freeze-drying apparatus is maintained at 10Pa at -32°C for 2 hours;

[0124] S4, the vacuum degree of the freeze-drying apparatus is maintained at 10Pa at -22°C for 1.2 hours;

[0125] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa and 23°C for 1 hour.

[0126] Example 7

[0127] S1. Add 0.20 kg of D-mannitol and 0.04 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, sonicate until completely dissolved, and concentrate under reduced pressure to a relative density of 1.13 at 70° C. to obtain a concentrated paste;

[0128] S2, placing the concentrated cream prepared by the above method into a mold, pre-freezing at -45°C in a freeze-drying device with a vacuum degree maintained at 10 Pa for 1 hour;

[0129] S3, the vacuum degree of the freeze-drying apparatus is maintained at 10Pa at -32°C for 2 hours;

[0130] S4, the vacuum degree of the freeze-drying apparatus is maintained at 10Pa at -22°C for 1.2 hours;

[0131] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa and 23°C for 1 hour.

[0132] Example 8

[0133] S1. Add 0.20 kg of D-mannitol and 0.06 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.13 at 70° C. to obtain a concentrated paste;

[0134] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0135] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0136] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0137] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0138] Example 5 is marked as Group 5; Example 6 is marked as Group 6; Example 7 is marked as Group 7; Example 8 is marked as Group 8. The freeze-dried SLT orodisintegrating tablets quality evaluation method recorded in the second aspect of the present invention were used to score the SLT orodisintegrating tablets. For each evaluation, 10 SLT orodisintegrating tablets were randomly selected from each group, and the total scores were calculated by group. 1 point was given for qualified and 0 point was given for unqualified. The scoring results are shown in Table 4.

[0139] Table 4

[0140]

[0141] Sucrose is used as a binder in this method. By analyzing Table 4, it can be seen that when the amount of sucrose is less than 0.01g, the adhesion of the Seluotong orodisintegrating tablet is poor, and cracking and splitting are prone to occur; when the amount of sucrose is 0.02-0.04kg, the Seluotong orodisintegrating tablet can maintain a good appearance and a good disintegration efficiency; when the amount of sucrose exceeds 0.04kg, the appearance of the Seluotong orodisintegrating tablet is significantly deteriorated, and a higher amount of sucrose will also reduce the disintegration rate of some tablets. In summary, when the amount of sucrose is 0.02kg and 0.04kg, the Seluotong orodisintegrating tablet can maintain a good appearance, and the optimal amount of sucrose in the present invention is about 0.02-0.04kg.

[0142] 20 tablets were randomly selected from each of Groups 5 to 8 for weight difference evaluation. The evaluation results are shown in Table 5.

[0143] Table 5

[0144]

[0145] Too little or too much sucrose dosage will affect the appearance of the SLT oro-disintegrating tablets, causing cracked edges and fragments. That is, when the sucrose dosage is 0.01kg or 0.06kg, the average tablet weight of the SLT oro-disintegrating tablets cannot meet the standard and cannot be used in production.

[0146] The hardness of Group 5 to Group 8 was evaluated, and the evaluation results are shown in Table 6.

[0147] Table 6

[0148]

[0149] When the amount of sucrose is too high or too low, the hardness of the SLT disintegrating tablets is low, which will cause cracking and flakes of the SLT disintegrating tablets. When the amount of sucrose is 0.02-0.04 kg, the hardness of the SLT disintegrating tablets is good, and cracking and flakes are not easy to occur.

[0150] 3. Determination of the density of concentrated paste

[0151] In order to eliminate the influence of other factors, this part of the embodiments follows the single factor variable principle, and the specific embodiments are as follows.

[0152] Example 9

[0153] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, sonicate until completely dissolved, and concentrate under reduced pressure to a relative density of 1.10 at 70° C. to obtain a concentrated paste;

[0154] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0155] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0156] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0157] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0158] Example 10

[0159] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0160] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0161] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0162] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0163] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0164] Embodiment 11

[0165] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until the extract is completely dissolved, and concentrate under reduced pressure to a relative density of 1.14 at 70° C. to obtain a concentrated paste;

[0166] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0167] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0168] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0169] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0170] Example 12

[0171] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.16 at 70°C to obtain S2. Place the concentrated paste prepared by the above method in a mold, and pre-freeze at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10 Pa.

[0172] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0173] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0174] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0175] Example 9 is marked as Group 9; Example 10 is marked as Group 10; Example 11 is marked as Group 11; Example 12 is marked as Group 12. The freeze-dried SLT orodisintegrating tablets quality evaluation method recorded in the second aspect of the present invention were used to score the SLT orodisintegrating tablets. For each evaluation, 10 SLT orodisintegrating tablets were randomly selected from each group, and the total scores were calculated by group. 1 point was given for qualified and 0 point was given for unqualified. The scoring results are shown in Table 7.

[0176] Table 7

[0177]

[0178] The relative density of the concentrated paste will directly affect the appearance and disintegration effect of the SLT orodisintegrating tablets. When the relative density of the concentrated paste is low (less than 1.12), the tablet shape of the SLT orodisintegrating tablets is poor and does not meet the quality requirements; when the concentration of the concentrated paste is too high (greater than 1.14), the appearance of the SLT orodisintegrating tablets deteriorates and the disintegration time becomes longer. Comprehensive analysis of the two scores shows that in order to obtain SLT orodisintegrating tablets with good tablet shape and disintegration time, the relative density of the concentrated paste should be limited to 1.12-1.14.

[0179] 20 tablets were randomly selected from each of Groups 9 to 12 for weight difference evaluation. The evaluation results are shown in Table 8.

[0180] Table 8

[0181]

[0182] When the relative density of the concentrated paste was low, the SLT oro-disintegrating tablets showed fragmentation and cracking, resulting in an average tablet weight far below the tablet specifications; when the relative density of the concentrated paste was 1.12-1.16, the SLT oro-disintegrating tablets could maintain a good average tablet weight and a low number of over-limits.

[0183] The hardness of Groups 9 to 12 was evaluated, and the evaluation results are shown in Table 9.

[0184] Table 9

[0185]

[0186]

[0187] When the relative density of the concentrated paste is 1.10, the hardness of the SLT disintegrating tablets is low, and therefore more edge cracks and flakes appear; when the relative density of the concentrated paste is 1.12-1.16, the hardness of different tablets is not much different, which is suitable for industrial production.

[0188] 3. Determination of primary drying temperature

[0189] In order to eliminate the influence of other factors, this part of the embodiments follows the principle of single factor variable. At the same time, in order to reduce the influence of the amount of D-mannitol, the amount of sucrose and the relative density of the concentrated paste on the appearance and disintegration time of the Sailuotong orodisintegrating tablets, the amount of D-mannitol, the amount of sucrose and the relative density of the concentrated paste are all controlled within the optimal range. The specific embodiments are as follows.

[0190] Example 13

[0191] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0192] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0193] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -36°C for 2 hours at a time;

[0194] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0195] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0196] Embodiment 14

[0197] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0198] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0199] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -34°C for 2 hours at a time;

[0200] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0201] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0202] Embodiment 15

[0203] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0204] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0205] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -32°C for 2 hours at a time;

[0206] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0207] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0208] Example 16

[0209] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0210] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0211] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -30°C for 2 hours at a time;

[0212] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0213] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0214] Embodiment 17

[0215] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0216] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0217] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the drying is performed at -28°C for 2 hours at a time;

[0218] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0219] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0220] Example 13 is marked as group 13; Example 14 is marked as group 14; Example 15 is marked as group 15; Example 16 is marked as group 16; Example 17 is marked as group 17. The freeze-dried SLT orodisintegrating tablets quality evaluation method recorded in the second aspect of the present invention were used to score the SLT orodisintegrating tablets. For each evaluation, 10 SLT orodisintegrating tablets were randomly selected from each group, and the total scores were calculated by group. 1 point was scored for qualified and 0 point was scored for unqualified. The scoring results are shown in Table 10.

[0221] Table 10

[0222]

[0223] When the primary drying temperature is relatively low, the color of the SLT disintegrating tablets is uniform, the shape is full, there is no crack edge, crack, melted flakes, or sticky flakes, but too low a temperature (less than -34°C) will slow down the disintegration rate of the SLT disintegrating tablets; when the primary drying temperature is close to the eutectic temperature, the SLT disintegrating tablets are prone to melt and sticky flakes, but as the primary drying temperature increases, the disintegration rate of the SLT disintegrating tablets gradually increases. Through a comprehensive investigation of the appearance evaluation and disintegration evaluation, when the primary drying temperature is selected at -34 to -32°C, the qualified rate of the tablet shape and the qualified rate of the disintegration time of the SLT disintegrating tablets are both high.

[0224] 20 tablets were randomly selected from each group 13 to group 17 for weight difference evaluation. The evaluation results are shown in Table 11.

[0225] Table 11

[0226]

[0227] When the primary drying temperature is between -36 and -32°C, the weight difference between the SLT oro-disintegrating tablets is small, that is, no SLT oro-disintegrating tablet exceeds the weight difference limit; when the primary drying temperature is between -30 and -28°C, the weight difference between the SLT oro-disintegrating tablets becomes larger, and some SLT oro-disintegrating tablets begin to exceed the weight difference limit.

[0228] The hardness of Groups 13 to 17 was evaluated, and the evaluation results are shown in Table 12.

[0229] Table 12

[0230]

[0231] In the above embodiments, the lower the primary drying temperature, the greater the hardness of the SLT disintegrating tablets. When the primary drying temperature is high, the SLT disintegrating tablets melt, causing a portion of the SLT disintegrating tablets in group 17 to have a lower hardness. At this time, the hardness difference between the tablets is large and cannot be used for industrial production.

[0232] 4. Determination of secondary drying temperature

[0233] After the concentrated paste is dried once, the water content is greatly reduced, and the tablets tend to be stable. In the subsequent drying process, when the drying temperature is higher than the eutectic point, the probability of melting of the Seloton orodisintegrating tablets becomes lower. On this basis, in order to shorten the freeze-drying time, save energy, and ensure that the Seloton orodisintegrating tablets are fully dried, the temperature of the secondary drying is now selected.

[0234] In order to eliminate the influence of other factors, this part of the examples follows the single factor variable principle. At the same time, in order to reduce the influence of the amount of D-mannitol, the amount of sucrose, the relative density of the concentrated paste and the primary drying on the appearance and disintegration time of the Sailuotong orally disintegrating tablets, the amount of D-mannitol, the amount of sucrose, the relative density of the concentrated paste and the primary drying temperature are all controlled within the optimal range. The specific examples are as follows.

[0235] Embodiment 18

[0236] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0237] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0238] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -34°C for 2 hours at a time;

[0239] S4, the vacuum degree of the freeze drying device is maintained at 10Pa, and secondary drying is performed at -26°C for 1.2 hours;

[0240] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0241] Embodiment 19

[0242] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0243] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0244] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -34°C for 2 hours at a time;

[0245] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -24°C for 1.2 hours;

[0246] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0247] Embodiment 20

[0248] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0249] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0250] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -34°C for 2 hours at a time;

[0251] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -22°C for 1.2 hours;

[0252] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0253] Embodiment 21

[0254] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0255] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0256] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -34°C for 2 hours at a time;

[0257] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -20°C for 1.2 hours;

[0258] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0259] Embodiment 22

[0260] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until completely dissolved, and concentrate under reduced pressure to a relative density of 1.12 at 70° C. to obtain a concentrated paste;

[0261] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0262] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -34°C for 2 hours at a time;

[0263] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -18°C for 1.2 hours;

[0264] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0265] Example 18 is marked as group 18; Example 19 is marked as group 19; Example 20 is marked as group 20; Example 21 is marked as group 21; Example 22 is marked as group 22. The freeze-dried SLT orodisintegrating tablets quality evaluation method recorded in the second aspect of the present invention were used to score the SLT orodisintegrating tablets. For each evaluation, 10 SLT orodisintegrating tablets were randomly selected from each group, and the total scores were calculated by group. 1 point was given for qualified and 0 point was given for unqualified. The scoring results are shown in Table 13.

[0266] Table 13

[0267]

[0268] After the first drying, the SLT disintegrating tablets tend to be stable, so the secondary drying temperature has less effect on the appearance and disintegration time of the SLT disintegrating tablets than the primary drying temperature. However, in order to prepare SLT disintegrating tablets with better appearance and qualified disintegration time, the temperature of the secondary drying should also be selected. When the secondary drying temperature is low (less than -24°C), the SLT disintegrating tablets are not fully dried, and melting will occur, affecting the score of the appearance evaluation; when the secondary drying temperature is high (greater than -18°C), the moisture dries too quickly during the secondary drying process, destroying the structure of the SLT disintegrating tablets, resulting in cracks and cracked edges. Comprehensive analysis shows that the temperature of the secondary drying should be selected between -24 and -20°C.

[0269] 20 tablets were randomly selected from each group 18 to group 22 for weight difference evaluation. The evaluation results are shown in Table 14.

[0270] Table 14

[0271]

[0272] When the secondary drying temperature was between -26 and -22°C, the weight difference between the Selotong orodisintegrating tablets was small, that is, no Selotong orodisintegrating tablet exceeded the weight difference limit; when the secondary drying temperature was -18°C, cracked edges and flakes were found in the Selotong orodisintegrating tablets, and the average tablet weight of the Selotong orodisintegrating tablets was significantly different from the specification of 60 mg. At the same time, some Selotong orodisintegrating tablets began to exceed the weight difference limit.

[0273] The hardness of Groups 18 to 22 was evaluated, and the evaluation results are shown in Table 15.

[0274] Table 15

[0275]

[0276] When the secondary drying temperature is too low, drying is incomplete, the SLT disintegrating tablets will melt, and SLT disintegrating tablets with lower hardness will appear; when the secondary drying temperature is between -24 and -20℃, the hardness difference between the SLT disintegrating tablets is small, which is suitable for industrial production; when the secondary drying temperature is too high, the hardness of the SLT disintegrating tablets is low, and melting, cracking and splitting will occur.

[0277] 5. Orthogonal experiment to optimize freeze-drying process

[0278] In order to select the best preparation process of freeze-dried Selotong orodisintegrating tablets, the color, morphology, crack edge, melting tablet, sticky tablet and disintegration time limit of Selotong orodisintegrating tablets were used as indicators for scoring, and the scoring method was 1 point for qualified and 0 points for unqualified. The grouping method was to randomly select 10 Selotong orodisintegrating tablets from each preparation method, that is, a group, and the total score of a single group was 60 points. The highest score was selected as the best preparation process. By analyzing Examples 5-8, it can be seen that the optimal amount of sucrose should be 0.02-0.04kg. Within this sucrose dosage range, the appearance qualification rate and disintegration qualification rate of Selotong orodisintegrating tablets are relatively stable, so the amount of D-mannitol, the relative density of concentrated paste, the primary drying temperature and the secondary drying temperature are selected as the influencing factors of the orthogonal test. The specific orthogonal factor levels are shown in Table 16, and the orthogonal experiment results are shown in Table 17. In the orthogonal test, the amount of sucrose used is 0.03kg.

[0279] Table 16

[0280]

[0281] Table 17

[0282]

[0283] By analyzing Table 7, we can know that the degree of influence on the quality of SLT orodisintegrating tablets is C>A>B>D.

[0284] The best selection is A2B3C1D1, that is, the dosage of D-mannitol is 0.20kg, the relative density of the concentrated paste is 1.14, the primary drying temperature is -34℃, and the secondary drying temperature is -24℃.

[0285] Based on the above analysis, the best preparation method of the Chinese medicine composition Sailuotong orodisintegrating tablets is:

[0286] S1. Add 0.20 kg of D-mannitol and 0.03 kg of sucrose to the extract of the traditional Chinese medicine composition prepared according to the method, perform ultrasonic treatment until the extract is completely dissolved, and concentrate under reduced pressure to a relative density of 1.14 at 70° C. to obtain a concentrated paste;

[0287] S2, placing the concentrated cream prepared by the above method into a mold, and pre-freezing it at -45°C for 1 hour in a freeze-drying device with a vacuum degree maintained at 10Pa;

[0288] S3, the vacuum degree of the freeze-drying device is maintained at 10Pa, and the freeze-drying is performed at -34°C for 2 hours at a time;

[0289] S4, the vacuum degree of the freeze-drying device is maintained at 10Pa, and secondary drying is performed at -24°C for 1.2 hours;

[0290] S5. The vacuum degree of the freeze-drying apparatus is maintained at 10 Pa, and the freeze-drying apparatus is dried for another hour at 23°C.

[0291] Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

Claims

1. A serotonin orally disintegrating tablet, characterized in that: The raw materials for making the Sailuotong orodisintegrating tablets include: 10 parts by weight of ginseng, 8 parts by weight of ginkgo leaves, 0.18 parts by weight of saffron, 0.15-0.25 parts by weight of D-mannitol and 0.02-0.04 parts by weight of sucrose; The preparation method of the Sailuotong orally disintegrating tablet comprises the following steps: S1. Take ginseng extract, ginkgo leaf extract, saffron extract, D-mannitol and sucrose, mix them thoroughly and then concentrate them under reduced pressure to a relative density of 1.12-1.14 at 70° C. to prepare a concentrated paste; S2, freeze-drying the concentrated paste to obtain the Sailuotong orodisintegrating tablets; The freeze drying comprises pre-freezing, primary drying, secondary drying and re-drying performed in sequence; The pre-freezing vacuum is 10Pa and the temperature is -45℃; The vacuum degree of primary drying is 10Pa and the temperature is -34~-30℃; The vacuum degree of secondary drying is 10Pa and the temperature is -24~-20℃; The vacuum degree of re-drying was 10 Pa and the temperature was 23°C.

2. The SLT orodispersible tablet according to claim 1, characterized in that: In step S1, the method for preparing the ginseng extract comprises the following steps: A. Grind 10 parts by weight of ginseng into powder, add ethanol and reflux extract twice, filter, and recover the solvent from the filtrate under reduced pressure to obtain an extract with a relative density of 1.12-1.14 at 70°C; B. Add the extract to water 2 to 6 times the weight of ginseng, stir well, cool and precipitate, and apply the obtained supernatant to macroporous adsorption resin. The macroporous adsorption resin is first rinsed with distilled water and then eluted with ethanol. The ethanol eluate is collected to obtain the ginseng extract.

3. The SLT orally disintegrating tablet according to claim 1, characterized in that: In step S1, the method for preparing the ginkgo leaf extract comprises the following steps: a. Grind 8 parts by weight of ginkgo leaves into coarse powder, soak them in warm ethanol, filter, soak the residue in warm ethanol again, filter, combine the two leaching solutions, and concentrate them under reduced pressure to a relative density of 1.02-1.04 at 70°C; b. Extracting with a mixed solution of ethyl acetate and n-butanol, combining the extracts, and recovering the solvent under reduced pressure to obtain the ginkgo leaf extract.

4. The SLT orodispersible tablet according to claim 1, characterized in that: In step S1, the method for preparing the saffron extract comprises the following steps: ①, take 0.18 parts by weight of saffron, add ethanol to soak, filter, add ethanol to soak again, filter, combine the two leaching solutions, and concentrate under reduced pressure to a relative density of 1.12-1.14 at 70°C; ②, adding water, applying macroporous adsorption resin, washing the macroporous adsorption resin with distilled water, and then washing with an ethanol column, collecting the ethanol eluate to obtain the saffron extract.

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