An oral dissolving system of tranexamic acid with improved bioavailability

Abstract

The application relates to an oral dissolving system of tranexamic acid with improved bioavailability, and relates to the technical field of medicines, comprising an oral dissolving film of tranexamic acid and an oral dissolving tablet of tranexamic acid. The design of the oral dissolving tablet and the oral dissolving film fully considers the requirements of different patient groups and the characteristics of drug absorption, the characteristics that the oral dissolving tablet and the oral dissolving film can be taken without water improve the compliance of patients, the problem of swallowing difficulty of traditional tablets is solved, the oral dissolving system has good convenience for patients who often travel or need to take medicine under waterless conditions; the oral dissolving system of tranexamic acid can rapidly disintegrate in the oral cavity, the drug is rapidly dispersed, the contact area with the oral mucosa is increased, the drug is absorbed through the oral mucosa and other pre-gastric regions, the bioavailability is improved, and the drug absorption speed is accelerated.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical technology, and in particular to a tranexamic acid oral dissolution system that improves bioavailability. Background Technology

[0002] Tranexamic acid belongs to the BCS class I molecules and has high solubility and permeability in water. However, in women aged 18-49, tranexamic acid... Its absolute bioavailability is approximately 45%, while The label indicates that the absorption rate of tranexamic acid after oral administration is 30% to 50% of the ingested dose, and its bioavailability is not affected by food intake. This means that due to the first-pass effect in the stomach, nearly 50-55% of the drug is metabolized and cannot exert its therapeutic effect.

[0003] Orally disintegrating systems, such as tablets or films, are increasingly popular due to their high bioavailability, rapid pregastric absorption, and high patient compliance. One of the key factors influencing compliance is that patients can ingest orally disintegrating tablets without the need for water. For many patients, especially the elderly, pediatricians, and those with dysphagia, orally disintegrating systems are more convenient than swallowing tablets. Orally disintegrating tablets are particularly valuable for patients who travel frequently or need to take medication when water is not always available. Once the drug is absorbed through the oral mucosa and other pregastric regions, its bioavailability increases, and the absorption rate accelerates, allowing the drug absorbed orally to enter the bloodstream more quickly.

[0004] Therefore, simply changing the formula ingredients can greatly improve bioavailability, enhance patient compliance, make it suitable for patients of all ages, and make it convenient to take while traveling.

[0005] CN106265581A solves the problem of low dissolution of tranexamic acid tablets produced by dissolving sodium dodecyl sulfate in binder slurry, spray granulation to obtain micronized tranexamic acid, and then mixing it with magnesium stearate tablets, which is produced by a wet method. It also improves the problems of large tablet weight difference and excessive tablet brittleness.

[0006] CN106265581B solves the problem of low dissolution of tranexamic acid tablets produced by wet granulation by dissolving sodium dodecyl sulfate in a binder slurry, spray granulating to obtain tranexamic acid micro powder, and then mixing it with magnesium stearate tablets. It also improves the problems of large tablet weight variation and excessive tablet brittleness.

[0007] CN110721169A discloses a method for preparing tranexamic acid tablets, specifically relating to the field of pharmaceutical manufacturing technology. This method effectively improves the stability of tranexamic acid drugs, increases the drug dissolution rate, achieves hemostasis and therapeutic effects more quickly, and enhances efficacy.

[0008] CN117180212A discloses a stable tranexamic acid tablet solid composition and a simple preparation method and use thereof.

[0009] However, the prior art does not solve the main problem of low bioavailability of tranexamic acid, because of the first-pass effect, a large amount of drugs are metabolized and cannot play a therapeutic role. Therefore, it is necessary to improve the bioavailability of tranexamic acid by oral route, and improve the compliance of patients. SUMMARY

[0010] In order to improve the bioavailability of tranexamic acid and the compliance of patients, the present application provides a tranexamic acid oral dissolving system for improving bioavailability.

[0011] The tranexamic acid oral dissolving system for improving bioavailability provided by the present application adopts the following technical solution: a tranexamic acid oral dissolving system for improving bioavailability, comprising a tranexamic acid oral dissolving film and a tranexamic acid oral dissolving tablet.

[0012] Preferably, the preparation raw materials of the tranexamic acid oral dissolving film include tranexamic acid, xylitol, polyethylene glycol, hydroxypropyl methyl cellulose, aspartame, sucralose, essence, propylene glycol and water.

[0013] Preferably, the tranexamic acid oral dissolving film is prepared by the following steps:

[0014] Under stirring, xylitol and polyethylene glycol are dissolved in water, aspartame, sucralose and spices are added and fully mixed, then tranexamic acid is added and mixed uniformly to obtain a main phase; hydroxypropyl methyl cellulose is dispersed in propylene glycol to obtain a dispersion liquid; the dispersion liquid is added to the main phase, and the two phases are mixed under stirring to hydrate, after removing entrained air, the mixture is coated on a casting film, dried, and the film is cut to obtain the tranexamic acid oral dissolving film.

[0015] Preferably, the hydroxypropyl methyl cellulose includes hydroxypropyl methyl cellulose with a dynamic viscosity of 6 centipoise and hydroxypropyl methyl cellulose with a dynamic viscosity of 15 centipoise.

[0016] Preferably, the preparation raw materials of the tranexamic acid oral dissolving tablet include tranexamic acid, mannitol, xylitol, carboxymethyl cellulose, crystalline cellulose, cross-linked polyvinylpyrrolidone, sucralose, aspartame, colloidal silicon dioxide and magnesium stearate.

[0017] Preferably, the tranexamic acid oral dissolving tablet is prepared by the following steps:

[0018] In a fluid bed granulator, add tranexamic acid, mannitol, xylitol, carboxymethyl cellulose and crystalline cellulose, spray water to the material, add cross-linked povidone to the material, spray water to the material, obtain granules, dry the obtained granules to obtain dried granules, add sucralose, aspartame and colloidal silicon dioxide to the dried granules and mix uniformly, add magnesium stearate and mix uniformly, and after tabletting, obtain tranexamic acid oral dissolving tablets.

[0019] The design of oral dissolving tablets and oral dissolving films fully considers the needs of different patient groups and the characteristics of drug absorption. For elderly patients, pediatric patients and patients with difficulty swallowing, the characteristic that they do not need to be taken with water greatly improves patient compliance and solves the problem of difficulty swallowing traditional tablets. For patients who often travel or need to take medicine in waterless conditions, the oral disintegration system has good convenience; oral dissolving tablets can rapidly disintegrate in the oral cavity, allowing the drug to be quickly dispersed, increasing the contact area with the oral mucosa, promoting the absorption of the drug through the oral mucosa and other pre-gastric regions, thereby improving the bioavailability and accelerating the absorption rate of the drug, allowing the drug to enter the blood more quickly and reducing the metabolic loss of the drug in the stomach; oral dissolving films, with their unique structure and ingredients, can better adhere to the oral mucosa, prolong the residence time of the drug on the mucosal surface and further improve the absorption efficiency of the drug.

[0020] Xylitol can provide a certain sweetness to the tranexamic acid oral dissolving film, improve the taste, and also synergize with polyethylene glycol to enhance the flexibility and stability of the film, allowing the tranexamic acid oral dissolving film to maintain a good physical state in the oral environment; aspartame and sucralose further optimize the taste, and the addition of spices makes the film have a pleasant odor, improving patient acceptance and compliance; hydroxypropyl methyl cellulose can form a structure with viscosity and strength, allowing the film to better adhere to the oral mucosa, increasing the contact time and area of the drug with the mucosa and promoting the absorption of tranexamic acid, thereby improving the bioavailability of the drug.

[0021] Mannitol has good solubility and water absorption, can quickly dissolve in the oral cavity, provides a good dispersion environment for the drug, and helps to improve the dissolution rate of the oral dissolving tablets of tranexamic acid; Xylitol not only improves the taste, but also interacts with other ingredients to enhance the stability and compressibility of the tablets; Carboxymethyl cellulose and crystalline cellulose as fillers and binders can better bind the drug particles together, and also promote disintegration in the oral cavity, promoting drug release; Cross-linked povidone has strong water absorption and swelling properties, which can be used as a disintegrant, rapidly absorbing water and swelling after contacting the oral saliva, causing the tablet to quickly disintegrate, increasing the contact area of the drug with the oral mucosa, thereby improving the bioavailability of the drug; Sucralose and aspartame as sweeteners can further optimize the taste and improve patient compliance; Colloidal silicon dioxide can improve the flowability of the material, making the material mixing more uniform; Magnesium stearate as a lubricant reduces friction during tabletting, ensuring smooth tabletting, while also helping to improve the surface finish and quality of the tablets; The prepared oral dissolving tablets of tranexamic acid can quickly disintegrate and dissolve in the oral cavity, allowing the drug to be quickly released and absorbed, effectively improving the bioavailability of the drug.

[0022] In a preferred embodiment, the mannitol and xylitol are in a co-crystal state, and the mannitol and xylitol co-crystal is prepared by the following steps:

[0023] The mannitol and xylitol are mixed and dispersed into an aqueous ethanol solution, stirred in a water bath to obtain a co-crystal suspension, the co-crystal suspension is reduced pressure filtered to obtain a solid product, and the solid product is dried to obtain a mannitol and xylitol co-crystal.

[0024] The mannitol and xylitol co-crystal has a special molecular arrangement and lattice energy, which can provide more dissolution sites and channels for tranexamic acid. In the aqueous environment of the oral cavity, water molecules can more easily penetrate into the interstitial space of the co-crystal lattice and interact with the tranexamic acid molecules, thereby promoting the dissociation and dissolution of tranexamic acid, increasing its solubility in the oral cavity, and thus facilitating faster absorption of the drug into the body and improving bioavailability.

[0025] In a preferred embodiment, the carboxymethyl cellulose and crystalline cellulose are modified by genipin crosslinking.

[0026] Genipin can change the molecular chain structure and spatial arrangement of carboxymethyl cellulose and crystalline cellulose, forming a network with certain pore structure. During oral dissolution, this network structure can better adsorb and retain saliva, providing a more favorable environment for the dissolution of tranexamic acid, while also enhancing the mechanical properties of the tablets to prevent them from breaking during storage.

[0027] In a preferred embodiment, the cross-linked povidone is modified to obtain modified cross-linked povidone, which is prepared by the following steps:

[0028] The poloxamer is dissolved in ethanol, stirred until the solution is clear and transparent, to obtain a poloxamer solution; the cross-linked povidone is dispersed in water, and after stirring, a cross-linked povidone dispersion is obtained; the poloxamer solution is added to the cross-linked povidone dispersion under stirring, and after the addition is completed, the reaction is carried out by water bath stirring, to obtain a mixed solution, which is centrifuged, and the precipitate is collected, washed with water until the supernatant is clear, and then dispersed in water, and ultrasonic treatment is carried out, to obtain a nanodispersion, which is subjected to homogenization treatment, to obtain a nanoparticle suspension, and after centrifugation, the precipitate is collected, and after freeze-drying, the modified cross-linked povidone is obtained.

[0029] The poloxamer has good solubility and surface activity, the poloxamer molecules can interact with the molecular chains of the cross-linked povidone, changing the surface properties and structure of the cross-linked povidone, and the hydrophilicity of the poloxamer helps to guide water into the tablet interior more quickly, shortening the disintegration time of the oral dissolving tablet, further promoting the release and absorption of the drug, thereby improving the bioavailability; the nanosizing treatment helps to improve the specific surface area of the cross-linked povidone, improving the compatibility with other ingredients and the stability of the tablet; the nanostructure also increases the contact area of the tablet with the oral mucosa, which is beneficial to the absorption of the drug in the oral cavity, thereby improving the bioavailability of the amoxicillin.

[0030] In summary, the present application includes at least one of the following beneficial technical effects:

[0031] 1. The design of the oral dissolving tablet and the oral dissolving film fully considers the needs of different patient groups and the characteristics of drug absorption, and for elderly patients, pediatric patients and patients with difficulty swallowing, the characteristics that they do not need to be taken with water greatly improve the patient's compliance, solving the problem of traditional tablet swallowing difficulty, and for patients who often travel or need to take medicine in waterless conditions, the oral disintegration system has good convenience; the oral dissolving tablet can rapidly disintegrate in the oral cavity, allowing the drug to disperse rapidly, increasing the contact area with the oral mucosa, promoting the absorption of the drug through the oral mucosa and other pre-gastric regions, thereby improving the bioavailability and accelerating the absorption speed of the drug, allowing the drug to enter the blood more quickly and reducing the metabolic loss of the drug in the stomach; the oral dissolving film can better adhere to the oral mucosa due to its unique structure and ingredients, prolonging the residence time of the drug on the mucosal surface and further improving the absorption efficiency of the drug.

[0032] 2. Mannitol and xylitol co-crystals have a special molecular arrangement and lattice energy, which can provide more dissolution sites and channels for tranexamic acid. In the aqueous environment of the oral cavity, water molecules can more easily penetrate into the lattice gap of the co-crystals and interact with the tranexamic acid molecules, thereby promoting the dissociation and dissolution of tranexamic acid, increasing its solubility in the oral cavity, and further facilitating faster absorption of the drug into the body and improving bioavailability.

[0033] 3. Genipin can change the molecular chain structure and spatial arrangement of carboxymethyl cellulose and crystalline cellulose, making it form a network with certain pore structure. During oral dissolution, this network structure can better adsorb and retain saliva, providing a more favorable environment for the dissolution of tranexamic acid, while also enhancing the mechanical properties of the tablets to prevent them from breaking during storage.

[0034] 4. Poloxamer has good solubility and surface activity. Poloxamer molecules can interact with the molecular chains of cross-linked povidone, changing the surface properties and structure of cross-linked povidone. The hydrophilicity of poloxamer helps to more quickly guide water into the interior of the tablet, shortening the disintegration time of the oral dissolution tablet, further promoting drug release and absorption, and thus improving bioavailability. Nanoparticle processing helps to increase the specific surface area of cross-linked povidone, improve compatibility with other ingredients, and enhance the stability of the tablet. This nanostructure also increases the contact area of the tablet with the oral mucosa, which is beneficial for drug absorption in the oral cavity, thereby improving the bioavailability of tranexamic acid. DETAILED DESCRIPTION

[0035] The present application discloses an oral dissolution system for tranexamic acid with improved bioavailability. The raw materials used in the present application, except for special instructions, can be obtained through commercially available materials. The present application is further described in detail below in conjunction with the examples:

[0036] Raw material description: Tranexamic acid (CAS No.: 1197-18-8), Xylitol (CAS No.: 87-99-0), PEG 6000 (CAS No.: 25322-68-3), Hydroxypropyl methylcellulose (CAS No.: 9004-64-2), Aspartame (CAS No.: 22839-47-0), Sucralose (CAS: 56038-13-2), Mannitol (CAS No.: 643-01-6), Carboxymethyl cellulose (CAS No.: 9000-11-7), Crystalline cellulose (CAS No.: 9004-34-6), Cross-linked povidone (CAS No.: 25249-54-1), Colloidal silicon dioxide (CAS No.: 10279-57-9), Magnesium stearate (CAS No.: 557-04-0), Genipin (CAS No.: 6902-77-8), Poloxamer (CAS No.: 9003-11-6).

[0037] Preparation of the oral dissolving film of tranexamic acid in Example 1

[0038] Dissolve the xylitol and polyethylene glycol 6000 (PEG 6000) in water under stirring, add the aspartame, sucralose and flavor and mix well, then add the tranexamic acid and mix well to obtain the main phase; disperse the hydroxypropyl methylcellulose 6 cps (HPMC 6 cps) and hydroxypropyl methylcellulose 15 cps (HPMC 15 cps) into propylene glycol to obtain a dispersion; add the dispersion into the main phase, mix the two phases under stirring to hydrate, remove the entrained air, then coat the mixture on a casting film with a thickness of 600 μm, cut the film after drying to obtain the oral dissolving film of tranexamic acid, and the specific ingredient amounts are shown in Table 1.

[0039] Table 1 Ingredient and amount of the oral dissolving film of tranexamic acid

[0040]

[0041]

[0042] Preparation of the oral dissolving tablet of tranexamic acid in Example 2

[0043] Add the tranexamic acid, mannitol, xylitol, carboxymethylcellulose and crystalline cellulose into the fluidized bed granulator, spray 260-300 g of water into the material at a speed of 20-30 g / min, add the cross-linked povidone into the material, spray about 280-320 g of water into the material at a speed of 10-20 g / min per minute, to obtain the granules, dry the obtained granules at a temperature of 50-55 °C until the water content is less than 2% to obtain the dried granules, add the sucralose, aspartame and colloidal silicon dioxide into the dried granules and mix well, add the magnesium stearate and mix well, use the tablet press to obtain the oral dissolving tablet of tranexamic acid after tabletting, and the specific ingredient amounts are shown in Table 2.

[0044] Table 2 Ingredient and amount of the oral dissolving tablet of tranexamic acid

[0045] No. Ingredient name Amount (mg / tablet) 1 Tranexamic acid 500.00 2 Mannitol 280.00 3 Xylitol 100.00 4 Carboxymethyl cellulose 71.00 5 Crystalline cellulose 100.00 6 Crospovidone 40.00 7 Sucralose 4.50 8 Aspartame 2.00 9 Colloidal silicon dioxide 2.00 10 Magnesium stearate 0.50

[0046] Example 3

[0047] Example 3 is based on Example 2, and the difference between Example 3 and Example 2 is only that the mannitol and xylitol in Example 3 are in a co-crystal state.

[0048] Preparation of the co-crystal of mannitol and xylitol

[0049] The mixture of mannitol and xylitol with a mass ratio of 2.8:1 was dispersed into 50% volume fraction of aqueous ethanol solution, so that the mass ratio of solute and solvent was 1:10, the mixture was stirred at 200 rpm for 3 h at 30°C to obtain a eutectic suspension, the eutectic suspension was filtered under reduced pressure to obtain a solid product, and the solid product was placed in an oven and dried at 40°C to obtain a mannitol and xylitol eutectic.

[0050] In the fluidized bed granulator, tranexamic acid, mannitol and xylitol eutectic, carboxymethyl cellulose and crystalline cellulose were added, 260-300 g of water was sprayed into the material at a speed of 20-30 g / min, cross-linked povidone was added to the material, and about 280-320 g of water was sprayed into the material at a speed of 10-20 g / min per minute to obtain granules, the obtained granules were dried at a temperature of 50-55°C until the water content was less than 2% to obtain dried granules, sucralose, aspartame and colloidal silicon dioxide were added to the dried granules and mixed uniformly, magnesium stearate was added and mixed uniformly, and after tabletting using a tablet press, tranexamic acid oral dissolving tablets were obtained.

[0051] Example 4

[0052] Example 4 is based on Example 3, and the only difference between Example 4 and Example 3 is that in Example 4, the carboxymethyl cellulose and crystalline cellulose are modified by cross-linking with genipin.

[0053] Preparation of modified carboxymethyl cellulose

[0054] Carboxymethyl cellulose was dissolved in 50% volume fraction of aqueous ethanol solution to obtain a carboxymethyl cellulose solution with a mass fraction of 5%, the pH of the carboxymethyl cellulose solution was adjusted to 8 using a phosphate buffer, genipin was added to the carboxymethyl cellulose solution with adjusted pH at 50°C, the mass ratio of carboxymethyl cellulose and genipin was 15:1, the reaction was stirred at 400 rpm for 4 h, the solvent was removed by rotary evaporation, and the product was dried in a vacuum drying oven at 60°C until the weight was constant to obtain modified carboxymethyl cellulose.

[0055] Preparation of modified crystalline cellulose The crystalline cellulose was pulverized to a particle size of 100 μm, the pulverized crystalline cellulose was dispersed in 50% volume fraction of aqueous ethanol solution and stirred at 500 rpm for 30 min to obtain a suspension, the pH of the suspension was adjusted to 8 using a phosphate buffer, genipin was added to the suspension with adjusted pH at 60°C, the mass ratio of microcrystalline cellulose and genipin was 20:1, the reaction was stirred at 500 rpm for 5 h, the solid product was obtained by filtration, washed with purified water, and dried in a vacuum drying oven at 70°C until the weight was constant to obtain modified crystalline cellulose.

[0056] In a fluidized bed granulator, add tranexamic acid, mannitol, xylitol, modified carboxymethyl cellulose and modified crystalline cellulose, spray 260-300 g of water into the material at a speed of 20-30 g / min, add cross-linked povidone to the material, spray about 280-320 g of water into the material at a speed of 10-20 g / min per minute, obtain granules, dry the obtained granules at a temperature of 50-55°C to a water content of less than 2%, obtain dried granules, add sucralose, aspartame and colloidal silicon dioxide to the dried granules and mix evenly, add magnesium stearate and mix evenly, use a tablet press to obtain tranexamic acid oral dissolving tablets after tabletting.

[0057] Example 5

[0058] Example 5 is based on Example 3, and the only difference between Example 5 and Example 3 is that in Example 5, the cross-linked povidone is modified to obtain modified cross-linked povidone.

[0059] Preparation of modified cross-linked povidone

[0060] Dissolve poloxamer in anhydrous ethanol, stir at a speed of 400 rpm until the solution is clear and transparent, obtain a poloxamer solution, the mass percentage content of the poloxamer solution is 1%; disperse cross-linked povidone in purified water, stir at a speed of 500 rpm for 4 h, obtain a cross-linked povidone dispersion, the mass percentage content of the cross-linked povidone dispersion is 2%; add the poloxamer solution to the cross-linked povidone dispersion at a stirring speed of 400 rpm, add it within 1 h, continue to stir at a speed of 500 rpm at 40°C for 5 h after adding, obtain a mixed solution, centrifuge the mixed solution, collect the precipitate, wash with ultrapure water until the supernatant is clear, disperse the washed precipitate in ultrapure water, use an ultrasonic cell crusher for ultrasonic treatment, obtain a nanodispersion after ultrasonic treatment for 30 min, perform high-pressure homogenization treatment on the nanodispersion, obtain a nanoparticle suspension, collect the precipitate after centrifugation, freeze-dry at -40°C, obtain modified cross-linked povidone.

[0061] In a fluidized bed granulator, add tranexamic acid, mannitol, xylitol, carboxymethyl cellulose and crystalline cellulose, spray 260-300 g of water into the material at a speed of 20-30 g / min, add modified cross-linked povidone to the material, spray about 280-320 g of water into the material at a speed of 10-20 g / min per minute, obtain granules, dry the obtained granules at a temperature of 50-55°C to a water content of less than 2%, obtain dried granules, add sucralose, aspartame and colloidal silicon dioxide to the dried granules and mix evenly, add magnesium stearate and mix evenly, use a tablet press to obtain tranexamic acid oral dissolving tablets after tabletting.

[0062] Performance test

[0063] (1) Dissolution test: The samples prepared in the examples and the commercially available randomly selected tranexamic acid tablets were subjected to dissolution test by paddle method in simulated oral saliva at 37°C using a dissolution tester. Each sample was tested three times, and the average value was taken after measurement. The results are recorded in Table 3.

[0064] (2) Disintegration test: The samples prepared in the examples and the commercially available randomly selected tranexamic acid tablets were subjected to disintegration test in simulated oral saliva at 37°C using a disintegration tester. Each sample was tested three times, and the average value was taken after measurement. The results are recorded in Table 3.

[0065] Table 3: Test results of dissolution and disintegration test

[0066]

[0067]

[0068] As can be seen from Table 3, the tranexamic acid oral dissolving tablets and the tranexamic acid oral dissolving films of Examples 1-5 have high dissolution and good disintegration performance, and can be rapidly absorbed through the oral mucosa and the pre-gastric region, thereby improving the bioavailability.

[0069] As can be seen from Table 3, the difference between Example 3 and Example 2 is only that the mannitol and xylitol in Example 3 are in a co-crystal state. Compared with Example 2, the dissolution and disintegration rate of Example 3 increase. This is because the co-crystal state of mannitol and xylitol can promote the dissolution of tranexamic acid, thereby promoting its absorption, and improving the solubility and disintegration rate.

[0070] As can be seen from Table 3, the difference between Example 4 and Example 2 is only that the carboxymethyl cellulose and crystalline cellulose in Example 4 are modified by cross-linking with genipin. Compared with Example 2, the dissolution of Example 4 increases, and the disintegration rate decreases. This is because the increase in cross-linking degree will affect the disintegration rate, but cross-linking can promote the formation of network structure, better retain and adsorb saliva, so that tranexamic acid can be better dissolved and absorbed.

[0071] As can be seen from Table 3, the difference between Example 5 and Example 2 is only that the cross-linked povidone in Example 5 is modified. Compared with Example 2, the disintegration rate and dissolution of Example 5 both increase. This is because the modified cross-linked povidone has better hydrophilicity and high specific surface area, which can make water quickly enter the inside of the tablet, shorten the drug disintegration time, and promote the absorption and utilization of tranexamic acid.

[0072] The commercially available tranexamic acid tablets have low dissolution rate and slow disintegration rate within 20 min. The film dosage forms and tablets prepared in Examples 1-5 have good dissolution rate and disintegration rate compared with the commercially available tranexamic acid tablets, which is beneficial to the absorption of tranexamic acid in the oral mucosa and the anterior region of the stomach, thereby achieving the effect of improving the bioavailability of tranexamic acid.

[0073] Stability study:

[0074] The developed examples were subjected to stability study under initial and accelerated stability storage conditions, especially the degradation study of tranexamic acid. The samples were analyzed using pharmacopoeia and effective impurity analysis methods. The results showed that the developed examples could be stably stored for 6 months under accelerated storage conditions and met the impurity standards of the British Pharmacopoeia and the United States Pharmacopoeia, and the test results are recorded in Table 4.

[0075] Table 4 Stability test results of tranexamic acid oral dissolving system

[0076]

[0077]

[0078] The specific embodiments are only an explanation of the present application, and are not a limitation of the present application. Through the above description, relevant personnel can make various changes and modifications without deviating from the technical idea of the present application. The technical scope of the present application is not limited by the content of the specification, and must be determined by the scope of the claims.

Claims

1. An oral dissolving system of tranexamic acid for improved bioavailability, characterized by: The tranexamic acid oral dissolving tablet is prepared by the following steps: In the fluid bed granulator, tranexamic acid, mannitol, xylitol, carboxymethyl cellulose and crystalline cellulose are added, 260-300 g of water is sprayed to the materials at a speed of 20-30 g / min, cross-linked povidone is added to the materials, about 280-320 g of water is sprayed to the materials at a speed of 10-20 g / min, to obtain granules, the obtained granules are dried at a temperature of 50-55 °C until the water content is less than 2%, to obtain dried granules, sucralose, aspartame and colloidal silicon dioxide are added to the dried granules and mixed uniformly, magnesium stearate is added and mixed uniformly, and the tranexamic acid oral dissolving tablet is obtained after tabletting by using a tablet press.

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