Preparation method of freeze-dried orally disintegrating tablet containing high-porosity auxiliary material

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a freeze-dried orally disintegrating tablet containing a high-porosity auxiliary material, the high-porosity auxiliary material is applied to the freeze-dried orally disintegrating tablet, and the problems that a large-specification high-water-solubility product is relatively high in hygroscopicity, easy to absorb moisture, poor in stability, difficult to form and the like are solved.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to a preparation method of freeze-dried orally disintegrating tablets containing highly porous excipients. The highly porous excipients are applied to freeze-dried orally disintegrating tablets to solve problems such as strong hygroscopicity, easy moisture absorption, poor stability, and difficult molding of large-scale highly water-soluble products. Background Art

[0002] Highly water-soluble products have problems such as strong hygroscopicity, easy moisture absorption, poor stability, and difficult molding. Using highly porous excipients can solve the above problems to a certain extent, and it also has a certain adsorption effect itself. Miglitol orally disintegrating tablets, as a typical highly water-soluble product, also have the above problems. The technical problem to be solved by the present invention is to provide a preparation method of orally disintegrating tablets containing highly porous excipients in view of the above-mentioned deficiencies of the prior art, taking Miglitol orally disintegrating tablets as an example.

[0003] Miglitol, as a type II diabetes treatment drug of the α-glucosidase inhibitor class, was first developed by Bayer Pharma AG in Germany in the early 1980s. The chemical name of Miglitol is: 1-(2-hydroxyethyl)-2-(hydroxymethyl)-3,4,5-piperidinetriol, with the molecular formula C8H17NO5, a molecular weight of 207.22, and the structural formula as follows:

[0004]

[0005] Due to the multiple pharmacological activities of Miglitol, such as significant hypoglycemic effect, small side effects, and good tolerance, it is an efficient and safe drug for the treatment of type II diabetes.

[0006] Currently, the main form of Miglitol used clinically is ordinary tablets. Domestic and foreign research and reports on Miglitol involve the study of film-coated tablets and orally disintegrating tablets. Miglitol has a structure similar to monosaccharides and has relatively serious hygroscopicity itself. Miglitol prepared with ordinary formulations requires strict storage requirements due to its strong hygroscopicity.

[0007] Chinese Patent Application No. CN202011105298.4 discloses a preparation method of miglitol tablets. In the pharmaceutical composition, there are 50 parts of miglitol, 15 - 50 parts of filling agent, 5 - 50 parts of disintegrant aid, and 0.5 - 2.5 parts of lubricant. The miglitol tablets prepared from the pharmaceutical composition have problems such as slow disintegration speed, slow absorption, and the need to drink water when taking the medicine. To solve the above problems, the freeze-dried orally disintegrating tablets of the present invention are an oral solid tablet that can disintegrate or dissolve in saliva. They have a fast disintegration speed, rapid absorption, and do not require drinking water after taking the medicine. They have characteristics such as fast disintegration and good absorption, and significantly improve the medication compliance for psychiatric patients, those with swallowing difficulties (the elderly and children), and patients with inconvenient water use in special environments. Therefore, they are very suitable for special patients such as psychiatric patients to take.

[0008] Chinese Patent Application No. CN201310043951.2 discloses a preparation method of miglitol sustained-release tablets. Aiming at the deficiencies of the existing miglitol drug administration methods, this method delays the release rate of miglitol in the body by using the method of compounding sodium-based montmorillonite and miglitol. However, the release speed of the sustained-release tablets is too slow, and there may be corresponding adverse reactions. If the drug dosage is too large, it is easy to produce gastrointestinal adverse reactions. Some may show nervous system adverse reactions, including abnormal taste, muscle pain, and dizziness. To solve the above problems, the freeze-dried orally disintegrating tablets of the present invention can first be directly placed in the mouth and can disintegrate and be absorbed under the action of saliva. Therefore, they have a rapid disintegration and absorption speed, and can also avoid the hepatic first-pass effect that cannot be avoided by ordinary oral preparations. Secondly, for some patients who cannot swallow whole ordinary tablets, this corresponding drug dosage form can be selected, which can greatly improve the medication compliance of children. Finally, since it is completely disintegrated in the mouth in advance, the drug residue in the intestine is reduced.

[0009] Chinese Patent Application No. CN200310108587.X discloses a miglitol orally disintegrating tablet for the treatment of type II diabetes. Aiming at the problems that film-coated tablets generally have a relatively high hardness, which often leads to an extended disintegration time limit, and the dissolution, absorption, and biological effects of the drug are also correspondingly slowed down, resulting in a decrease in bioavailability, etc., this method overcomes the defects of the above-mentioned prior art and provides a miglitol orally disintegrating tablet that is convenient to take and has a significant effect and its preparation method. However, it does not solve the problems of strong hygroscopicity, easy moisture absorption, poor stability, and difficult forming of miglitol orally disintegrating tablets.

[0010] Miglitol is a drug with strong hygroscopicity. Tablets prepared by ordinary methods such as direct compression method, wet granulation compression method, and dry granulation compression method are prone to absorb moisture during storage, affecting the stability of the drug, and there are problems such as a decrease in content, a decrease in dissolution rate, and an increase in related substances, which seriously affect the quality of miglitol tablets and the safety of medication.

[0011] Therefore, there is an urgent need to develop a preparation method for freeze-dried orally disintegrating tablets containing high-porosity excipients, and apply the high-porosity excipients to freeze-dried orally disintegrating tablets to solve the problems of difficult forming and easy moisture absorption of large-scale and highly water-soluble freeze-dried tablets. This is of great significance for the product quality of miglitol freeze-dried orally disintegrating tablets and improving the drug use safety of patients. Summary of the Invention

[0012] The technical problem to be solved by the present invention is to provide a preparation method for freeze-dried orally disintegrating tablets containing high-porosity excipients in view of the above-mentioned deficiencies of the prior art. The preparation process of this method is simple and suitable for large-scale batch production; this method prepares miglitol freeze-dried orally disintegrating tablets by using a method of compounding high-porosity excipients with miglitol, significantly improving the utilization rate of miglitol drugs, greatly increasing the compliance of patients taking the medicine, and alleviating the problems of strong hygroscopicity, easy moisture absorption, poor stability and difficult forming of miglitol freeze-dried orally disintegrating tablets.

[0013] The purpose of the present invention is to provide a preparation method for freeze-dried orally disintegrating tablets containing high-porosity excipients. By using the freeze-drying process to prepare miglitol orally disintegrating tablets, the disintegration speed, taste and patient medication compliance of the orally disintegrating tablets are improved.

[0014] In the first aspect of the present invention, a preparation method for freeze-dried orally disintegrating tablets containing high-porosity excipients is provided, including the following steps:

[0015] S1. Mix miglitol, high-porosity excipients and other excipients to prepare a uniformly dispersed liquid suspension;

[0016] S2. Dispense the liquid suspension into the blister of the tablet;

[0017] S3. After dispensing, quickly carry out liquid nitrogen quick-freezing and forming at -70 to -100 °C;

[0018] S4. After quick-freezing and forming, put it into a vacuum freeze-dryer for freeze-drying, and then carry out inner packaging heat-sealing to obtain miglitol freeze-dried orally disintegrating tablets.

[0019] Preferably, the high-porosity excipients include one or more of magnesium aluminum silicate, magnesium aluminum silicate, magnesium silicate, fumed silica, colloidal silica, etc.;

[0020] Preferably, step S1 includes the following steps:

[0021] S11. Add the excipient into purified water to dissolve and form a binder solution;

[0022] S12. Add the flavoring agent, high-porosity excipients and miglitol into the binder solution, and stir to prepare a uniformly dispersed liquid suspension;

[0023] Preferably, step S12 further includes: subjecting the liquid medicine suspension to high-speed shearing by a high-speed shearing disperser to make the dispersion of the liquid medicine suspension more uniform.

[0024] Preferably, the temperature for quick freezing in step S3 is -80°C.

[0025] Preferably, step S4 includes the following steps: pre-cooling a freeze dryer in advance, quickly putting the solidified liquid medicine suspension formed by quick freezing into the freeze dryer, keeping it for a period of time in a low-temperature environment, then through a primary drying stage and an analytical drying stage, and then heat-sealing the inner package to obtain the miglitol freeze-dried orally disintegrating tablets.

[0026] In the second aspect of the present invention, there is provided a miglitol freeze-dried orally disintegrating tablet prepared by a method for preparing a freeze-dried orally disintegrating tablet containing a high-porosity excipient, which, by mass percentage, includes: 15%-40% of miglitol; 60%-85% of excipients; the excipients include one or more of high-porosity excipients, excipients, disintegrants, and flavoring agents.

[0027] Preferably, by mass percentage, it includes: 15%-40% of miglitol; 10-20% of high-porosity excipients; 30%-50% of excipients; 2-5% of flavoring agents; 0-10% of disintegrants.

[0028] Preferably, by mass percentage, it includes: 30%-40% of miglitol; 15-20% of high-porosity excipients; 40%-50% of excipients; 2-3% of flavoring agents; 0-10% of disintegrants.

[0029] However, any lower limit can be combined with any upper limit to form a range not explicitly recorded; and any lower limit can be combined with other lower limits to form a range not explicitly recorded, and similarly any upper limit can be combined with any other upper limit to form a range not explicitly recorded. In addition, although not explicitly recorded, each point or single value between the range endpoints is included in this range. Thus, each point or single value can be used as its own lower limit or upper limit and combined with any other point or single value or combined with other lower limits or upper limits to form a range not explicitly recorded.

[0030] Preferably, the high-porosity excipients include one or more of magnesium aluminum silicate, aluminum magnesium silicate, magnesium silicate, fumed silica, colloidal silica, etc.; the excipients include one or more of pullulan, polyvinyl alcohol, polyethylene glycol 4000, polyvinylpyrrolidone, gelatin, hypromellose, hydroxypropyl cellulose, mannitol, sorbitol, trehalose, and erythritol; the disintegrants include one or more of corn starch, crospovidone, sodium carboxymethyl starch, carboxymethyl cellulose, cross-linked sodium carboxymethyl cellulose, etc.; the flavoring agents include one or more of acesulfame potassium, sucralose, aspartame, sodium saccharin, etc.

[0031] Beneficial effects:

[0032] (1) By adopting the freeze-drying process to prepare miglitol freeze-dried orally disintegrating tablets, firstly, a stable skeleton structure is formed through pre-freezing. After removing water by freeze-drying, the finished product is porous and loose. Therefore, it has good water rehydration in the oral cavity, solves the problems of slow disintegration and strong sandiness of the freeze-dried orally disintegrating tablets prepared by the compression method, significantly improves the disintegration speed and taste of the freeze-dried orally disintegrating tablets, and has high patient compliance;

[0033] (2) By using liquid nitrogen ultra-low temperature quick-freezing to quickly solidify the liquid medicine suspension, the freezing time is short, the production efficiency is improved, and it is suitable for large-scale production.

[0034] (3) By using high-porosity excipients in the freeze-dried orally disintegrating tablets, the difficulties of difficult molding and easy moisture absorption of large-scale and highly water-soluble products are solved. Description of the drawings

[0035] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required to be used in the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0036] Figure 1 Front view of the miglitol orally disintegrating tablet made by the freeze-drying process of the present invention;

[0037] Figure 2 Back view of the miglitol orally disintegrating tablet made by the freeze-drying process of the present invention; Detailed implementation manners

[0038] It should be noted that the following detailed description is illustrative and is intended to provide further description of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present application belongs.

[0039] The technical solutions of the present invention will be clearly and completely described below in conjunction with specific embodiments. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the protection scope of the present invention.

[0040] Example 1

[0041] This example provides a method for preparing a freeze-dried orally disintegrating tablet containing high-porosity excipients, which includes the following steps:

[0042] S1. Mix miglitol and high-porosity excipients to form a uniformly dispersed drug liquid suspension.

[0043] Preferably, the high-porosity auxiliary material includes: one or more of magnesium aluminum silicate, magnesium aluminum silicate, magnesium silicate, fumed silica, gel silica, etc.; the excipient includes: one or more of pullulan, polyvinyl alcohol, polyethylene glycol 4000, povidone, gelatin, hydroxypropyl methylcellulose, hydroxypropyl cellulose, mannitol, sorbitol, trehalose and erythritol; the disintegrant includes: one or more of corn starch, crospovidone, sodium carboxymethyl starch, carboxymethyl cellulose, cross-linked sodium carboxymethyl cellulose, etc.; the flavoring agent includes: one or more of acesulfame potassium, sucralose, aspartame, saccharin sodium, etc.

[0044] In a specific embodiment, hydroxypropyl cellulose is dissolved in purified water at 60° C., and then mannitol, sucralose, miglitol, and magnesium aluminum silicate are added, and the mixture is evenly dispersed by high-speed stirring and shearing to prepare a drug liquid suspension.

[0045] S2. Pack the liquid suspension into tablet blisters.

[0046] In a specific embodiment, the drug liquid suspension obtained in step S1 is filled into tablet blisters, and the filling amount is controlled to 0.4 g / hole.

[0047] S3. After the subpackaging is completed, the liquid nitrogen is quickly frozen at -70 to -100°C to form the product. The liquid medicine suspension is quickly solidified by ultra-low temperature quick freezing with liquid nitrogen, and the freezing time is short, which improves the production efficiency and is suitable for large-scale production.

[0048] In a specific embodiment, the tablet blisters containing the drug liquid suspension obtained in step S2 are quickly frozen in liquid nitrogen at -80°C.

[0049] S4. After quick freezing and forming, the product is placed in a vacuum freeze dryer for freeze drying, and then heat-sealed to obtain freeze-dried orodisintegrating tablets of miglitol. A stable skeleton structure is formed by pre-freezing, and then the water is removed by freeze drying. The finished product is loose and porous, so it has good rehydration properties in the oral cavity, which solves the problems of slow disintegration and strong sandy feeling of orodisintegrating tablets prepared by the compression method, significantly improves the disintegration speed and taste of the orodisintegrating tablets, and has high patient compliance.

[0050] In a specific embodiment, the freeze dryer is precooled to -30°C in advance, and the quick-frozen solid drug liquid suspension obtained in step S3 is quickly placed in the precooled freeze dryer and kept at -30°C for 30 minutes. In the primary drying stage, a vacuum of 0.2 mbar is set, and the temperature is raised to 0°C in 3 hours and continued for 6 hours; in the analytical drying stage, an extreme vacuum is set, the temperature is raised to 30°C, and continued for 2 hours; and then the inner package is heat-sealed to obtain the miglitol freeze-dried orally disintegrating tablets.

[0051] In summary, in this embodiment, the miglitol orally disintegrating tablets are prepared by freeze-drying process. First, a stable skeleton structure is formed by pre-freezing. After removing moisture by freeze-drying, the finished product is porous and loose. Therefore, it has good water rehydration property in the mouth, solving the problems of slow disintegration and strong sandiness of the orally disintegrating tablets prepared by compression method, significantly improving the disintegration speed and taste of the orally disintegrating tablets, and having high patient compliance. In this embodiment, the liquid medicine suspension is quickly solidified by ultra-low temperature quick-freezing with liquid nitrogen, with a short freezing time, improving the production efficiency and being suitable for large-scale production.

[0052] Example 2

[0053] This embodiment provides a method for preparing freeze-dried orally disintegrating tablets containing high-porosity excipients, including: 50 mg of miglitol, 12 mg of gelatin, 45 mg of mannitol, 30 mg of magnesium aluminum silicate, 4 mg of acesulfame potassium, 15 mg of corn starch, 244 mg of purified water (removed after freeze-drying), with a total of 400 mg.

[0054] The miglitol orally disintegrating tablets of this embodiment are prepared by the above preparation method, and the specific steps are as follows:

[0055] (1) Dissolve gelatin in purified water at 60°C, then add mannitol, magnesium aluminum silicate, and miglitol and stir to dissolve, and use high-speed shearing to make it disperse evenly to prepare a liquid medicine suspension;

[0056] (2) Fill the liquid medicine suspension obtained in step (1) into the blisters of the tablets, and control the filling amount at 0.4 g / hole;

[0057] (3) Freeze and form the blisters of the tablets carrying the liquid medicine suspension of miglitol at -80°C with liquid nitrogen;

[0058] (4) Quickly put the solidified miglitol liquid medicine suspension obtained in step (3) into a pre-cooled freeze-dryer, keep it in a low-temperature environment of -30°C for 30 minutes, set the vacuum at 0.2 mbar in the first drying stage, heat up to 0°C in 3 hours, and continue for 6 h; set the ultimate vacuum in the analytical drying stage, heat up to 30°C, and continue for 2 h; then perform inner packaging heat sealing to obtain the freeze-dried miglitol orally disintegrating tablets.

[0059] Example 3

[0060] The difference between this Example 3 and Example 2 is that the types of high-porosity excipients are different. Magnesium aluminum silicate is adjusted to magnesium aluminum metasilicate, and the rest is the same as in Example 2.

[0061] Specifically, this comparative example provides a method for preparing a freeze-dried orally disintegrating tablet containing a high-porosity excipient, including: 50 mg miglitol, 12 mg gelatin, 45 mg mannitol, 30 mg magnesium aluminum silicate, 4 mg acesulfame potassium, 15 mg corn starch, 244 mg purified water (removed after freeze-drying), totaling 400 mg.

[0062] Example 4

[0063] The difference between this Example 4 and Example 2 is that the type of high-porosity excipient is different. Magnesium aluminum silicate is adjusted to magnesium silicate, and the rest is the same as in Example 2.

[0064] Specifically, this comparative example provides a method for preparing a freeze-dried orally disintegrating tablet containing a high-porosity excipient, including: 50 mg miglitol, 12 mg gelatin, 45 mg mannitol, 30 mg magnesium silicate, 4 mg acesulfame potassium, 15 mg corn starch, 244 mg purified water (removed after freeze-drying), totaling 400 mg.

[0065] Example 5

[0066] The difference between this Example 5 and Example 2 is that the type of high-porosity excipient is different. Magnesium silicate is adjusted to fumed silica, and the rest is the same as in Example 2.

[0067] Specifically, this comparative example provides a method for preparing a freeze-dried orally disintegrating tablet containing a high-porosity excipient, including: 50 mg miglitol, 12 mg gelatin, 45 mg mannitol, 30 mg fumed silica, 4 mg acesulfame potassium, 15 mg corn starch, 244 mg purified water (removed after freeze-drying), totaling 400 mg.

[0068] Example 6

[0069] The difference between this Example 6 and Example 2 is that the type of high-porosity excipient is different. Fumed silica is adjusted to colloidal silica, and the rest is the same as in Example 2.

[0070] Specifically, this comparative example provides a method for preparing a freeze-dried orally disintegrating tablet containing a high-porosity excipient, including: 50 mg miglitol, 12 mg gelatin, 45 mg mannitol, 30 mg colloidal silica, 4 mg acesulfame potassium, 15 mg corn starch, 244 mg purified water (removed after freeze-drying), totaling 400 mg.

[0071] Results and Analysis

[0072] I. The miglitol orally disintegrating tablet of Example 2 was made into a white freeze-dried tablet by freeze-drying process (see Figure 1 and Figure 2 ), with a diameter of about 15 mm and a thickness of about 4.5 mm.

[0073] II. Comparative results of the characteristics of miglitol freeze-dried orally disintegrating tablets in Examples 1-6. Through analysis, it can be seen that:

[0074] (1) The miglitol orally disintegrating tablets prepared by the freeze-drying process in Example 1 have no sandy feeling and a fast disintegration speed compared to the miglitol orally disintegrating tablets prepared by the reference compression method.

[0075] Disintegration time: refers to the time when an oral solid preparation completely disintegrates, dissolves, or becomes fragmented under specified conditions (such as water at 37°C).

[0076] (2) In Examples 2-6, magnesium aluminum silicate, magnesium aluminum silicate, magnesium silicate, fumed silica, and colloidal silica were used as high-porosity excipients respectively. After freeze-drying, the problem of difficult tablet formation was solved. By using high-porosity excipients in freeze-dried orally disintegrating tablets, problems such as strong hygroscopicity, easy moisture absorption, poor stability, and difficult molding of large-scale highly water-soluble products were solved.

[0077] Finally, it should be noted that the above are only the preferred embodiments of the present invention. It should be understood that the present invention is not limited to the form disclosed herein, and should not be regarded as excluding other embodiments, but can be used in various other combinations, modifications, and environments, and can be changed within the scope of the concept described herein through the above teachings or the technology or knowledge in related fields. Any changes and modifications made by those skilled in the art without departing from the spirit and scope of the present invention shall fall within the protection scope of the appended claims of the present invention.

Claims

1. A preparation method of freeze-dried orally disintegrating tablets containing high-porosity excipients, characterized in that the high-porosity excipients are applied to the freeze-dried orally disintegrating tablets, including the following steps: S1. Mix miglitol, high-porosity excipients and other excipients to form a uniformly dispersed liquid suspension; S2. Dispense the liquid suspension into the blisters of the tablets; S3. After dispensing, quickly carry out liquid nitrogen quick-freezing and shaping at -70 to -100 °C; S4. After quick-freezing and shaping, put it into a vacuum freeze dryer for freeze-drying, and then carry out inner packaging heat sealing to obtain miglitol freeze-dried orally disintegrating tablets.

2. The preparation method of freeze-dried orally disintegrating tablets containing high-porosity excipients according to claim 1, characterized in that: S11. Add the excipient to purified water to dissolve and form an adhesive solution; S12. Add the flavoring agent, high-porosity excipients and miglitol to the adhesive solution, and stir to form a uniformly dispersed liquid suspension.

3. The preparation method of freeze-dried orally disintegrating tablets containing high-porosity excipients according to claim 2, characterized in that step S12 further includes: the liquid suspension is subjected to high-speed shearing by a high-speed shear disperser to make the liquid suspension more uniformly dispersed.

4. The preparation method of freeze-dried orally disintegrating tablets containing high-porosity excipients according to claim 1, characterized in that the temperature of quick-freezing in step S3 is -80 °C.

5. The preparation method of freeze-dried orally disintegrating tablets containing high-porosity excipients according to claim 1, characterized in that step S4 includes the following steps: pre-cool the freeze dryer in advance, quickly put the solidified liquid suspension after quick-freezing and shaping into the freeze dryer, keep it in a low-temperature environment for a period of time, then go through a primary drying stage and an analytical drying stage, and then carry out inner packaging heat sealing to obtain miglitol freeze-dried orally disintegrating tablets.

6. Miglitol freeze-dried orally disintegrating tablets prepared by the preparation method of freeze-dried orally disintegrating tablets containing high-porosity excipients according to any one of claims 1-5, by mass percentage, including: 15%-40% of miglitol; 60%-85% of excipients.

7. The miglitol freeze-dried orally disintegrating tablets according to claim 6, characterized in that by mass percentage, including: 15%-40% of miglitol; 10-20% of high-porosity excipients; 30%-50% of excipient; 2-5% of flavoring agent; 0-10% of disintegrant.

8. The miglitol freeze-dried orally disintegrating tablets according to claim 6, characterized in that by mass percentage, including: 30%-40% of miglitol; 15-20% of high-porosity excipients; 40%-50% of excipient; 2-3% of flavoring agent; 0-10% of disintegrant.

9. The miglitol freeze-dried orally disintegrating tablets according to claim 6, characterized in that The high-porosity excipients include one or more of magnesium aluminum silicate, aluminum magnesium silicate, magnesium silicate, fumed silica, colloidal silica, etc.; the excipients include one or more of pullulan, polyvinyl alcohol, polyethylene glycol 4000, polyvinylpyrrolidone, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, mannitol, sorbitol, trehalose, and erythritol; the disintegrants include one or more of corn starch, crospovidone, sodium carboxymethyl starch, carboxymethylcellulose, croscarmellose sodium, etc.; the flavoring agents include one or more of acesulfame potassium, sucralose, aspartame, sodium saccharin, etc.

10. The miglitol lyophilized orally disintegrating tablets prepared by the method for preparing a lyophilized orally disintegrating tablet containing high-porosity excipients according to any one of claims 1-5 or the miglitol lyophilized orally disintegrating tablets according to any one of claims 6-9 have various pharmacological activities, significant hypoglycemic effects, few side effects, and good tolerance, etc. It is characterized in that By using high-porosity excipients in lyophilized orally disintegrating tablets, problems such as strong hygroscopicity, easy moisture absorption, poor stability, and difficult molding of large-scale highly water-soluble products are solved.

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