Polyethylene glycol disintegrating tablet and preparation method thereof

Abstract

The invention relates to a polyethylene glycol disintegrating tablet. The polyethylene glycol disintegrating tablet is prepared from the following raw materials in parts by mass: content, modified polyethylene glycol, a disintegrating agent and an auxiliary agent, wherein the modified polyethylene glycol is obtained by reacting n-octylamine with long-chain alkyl acrylate, then reacting with ethylenediamine and then reacting with activated polyethylene glycol; the activated polyethylene glycol is obtained by reacting monomethyl ether polyethylene glycol with N, N-carbonyldiimidazole. Modified polyethylene glycol is adopted as a package, the modified polyethylene glycol is prepared by reacting n-octylamine with long-chain alkyl acrylate and then reacting with ethylenediamine, and hydrophobic segments such as long-chain alkyl are introduced into a PEG long chain. The hydrophilic-lipophilic balance of the material can be regulated and controlled by introducing the hydrophobic segment; enhanced interaction in molecular chains endows the tablet with sufficient mechanical strength.

Description

Technical Field

[0001] This invention relates to the field of materials technology, and in particular to a polyethylene glycol disintegrating tablet and its preparation method. Background Technology

[0002] Disintegrating tablets are solid dosage forms that rapidly break down, disperse, and release their contents upon contact with an aqueous environment (such as water or bodily fluids). These tablets are widely used in pharmaceuticals (e.g., immediate-release tablets, effervescent tablets), daily chemical products (e.g., dishwasher detergent tablets, effervescent bath tablets), and industrial cleaning agents. Their performance is primarily determined by the speed and completeness of disintegration, as well as the tablet's sufficient mechanical strength during storage and transportation.

[0003] In existing technologies, polyethylene glycol (PEG) is often used as a binder and matrix material for disintegrating tablets due to its good water solubility, low toxicity, film-forming properties, and broad compatibility. Through hot melt casting tableting or dry tableting processes, PEG can effectively encapsulate and bind contents (such as foaming agents, acid sources, active ingredients, etc.) into a mold.

[0004] However, disintegration tableting using unmodified conventional PEG as the main matrix material has the following significant technical drawbacks: The contradiction between disintegration properties and mechanical strength: To obtain sufficient tablet hardness and abrasion resistance to prevent breakage during packaging and transportation, higher molecular weight PEG or increased dosage is usually required. However, this leads to a decrease in the dissolution and melting rate of PEG in water, resulting in a denser gel layer that hinders further water penetration and overall tablet disintegration, leading to prolonged disintegration time or even incomplete disintegration. Conversely, if low molecular weight PEG is used or the dosage is reduced in pursuit of rapid disintegration, the tablets become soft and brittle, failing to meet practical application requirements.

[0005] Compatibility and encapsulation stability issues with specific contents: For certain highly polar or ionic contents (such as carbonates, citrates, etc.), the polar segments of conventional PEG may not interact sufficiently with them, leading to content migration or moisture absorption during long-term storage, affecting tablet stability. Furthermore, the relatively simple chemical structure of PEG limits the means of finely controlling its disintegration behavior.

[0006] To overcome these problems, researchers have tried various methods, such as compounding multiple PEGs with different molecular weights, adding large amounts of disintegrants, or using other types of synthetic polymers. However, these methods often only address the symptoms, not the root cause. The addition of large amounts of excipients may introduce new compatibility issues, increase costs and process complexity, and have limited effect on fundamentally improving the disintegration properties of the PEG matrix itself.

[0007] Therefore, there is an urgent need in this field for a new type of matrix material that can inherit the excellent sheet-forming properties and biocompatibility of PEG, while fundamentally solving its disadvantages of slow disintegration and easy formation of gel barriers. Summary of the Invention

[0008] This invention provides a polyethylene glycol (PEG) disintegrating tablet using modified PEG as a coating. The modified PEG is prepared by reacting n-octylamine with long-chain alkyl acrylates, followed by a reaction with ethylenediamine. Long-chain alkyl hydrophobic segments and other groups are introduced into the PEG long chain. The introduction of hydrophobic segments can regulate the hydrophilic-lipophilic balance of the material; while the enhanced interactions within the molecular chain endow the tablet with sufficient mechanical strength.

[0009] Therefore, it is necessary to provide a polyethylene glycol disintegrating tablet, wherein the raw material of the polyethylene glycol disintegrating tablet comprises the following components in parts by weight: 25-35 contents 6-15 parts of modified polyethylene glycol 7-15 parts disintegrant Additives: 0.5-10 parts; The modified polyethylene glycol is obtained by reacting n-octylamine with long-chain alkyl acrylate, then with ethylenediamine, and finally with activated polyethylene glycol. The activated polyethylene glycol is obtained by reacting monomethyl ether polyethylene glycol with N,N-carbonyl diimidazole.

[0010] Furthermore, the contents are selected from one or more of sodium carbonate, sodium bicarbonate, sodium percarbonate, and citric acid.

[0011] Furthermore, the disintegrant is selected from one or more of hydroxypropyl cellulose and microcrystalline cellulose.

[0012] Furthermore, the long-chain alkyl acrylate is selected from one or more of tetradecyl acrylate, hexadecyl acrylate, and octadecyl acrylate.

[0013] Furthermore, the additive is selected from one or more of lubricants and flow aids.

[0014] The present invention also provides a method for preparing the polyethylene glycol disintegrating tablet, the method comprising the following steps: S1. Mix n-octylamine with long-chain alkyl acrylate and heat to react, to obtain intermediate product 1; S2. Mix intermediate product 1 with ethylenediamine and heat to react, to obtain intermediate product 2; S3. Mix monomethyl ether polyethylene glycol with N,N-carbonyl diimidazole and react at room temperature under the protection of an inert gas to obtain activated polyethylene glycol; S4. Mix intermediate product 2 with activated polyethylene glycol and react at room temperature to obtain modified polyethylene glycol; S5. Mix the modified polyethylene glycol and the contents, then add the remaining ingredients, stir and granulate, mix and compress to obtain the polyethylene glycol disintegrating tablet.

[0015] Furthermore, in step S1, the heating temperature is 30-40°C; In step S2, the heating temperature is 35-40℃.

[0016] Further, in step S1, the mass ratio of n-octylamine to long-chain alkyl acrylate is 1-2:3-5.

[0017] Further, in step S2, the mass ratio of intermediate product 1 to ethylenediamine is 1-2:0.1-1.

[0018] In step S3, the mass ratio of the monomethyl ether polyethylene glycol to N,N-carbonyl diimidazole is 1-3:1-2; In step S4, the mass ratio of intermediate product 2 to activated polyethylene glycol is 1-2:0.8-1.5.

[0019] The present invention has the following beneficial effects: This invention uses modified polyethylene glycol to encapsulate sodium carbonate, sodium bicarbonate, sodium percarbonate, citric acid, and other materials, and then compresses them to obtain disintegrating tablets. The modified polyethylene glycol first undergoes a Michael addition reaction with n-octylamine and long-chain alkyl acrylate, then grafts the ester group of the intermediate product with ethylenediamine, and finally reacts with CDI-activated polyethylene glycol through an amino group, thereby introducing long-chain alkyl hydrophobic segments into the molecular chain to obtain modified polyethylene glycol containing a three-dimensional network structure.

[0020] Long-chain alkyl hydrophobic segments can improve the hydrophobicity of modified polyethylene glycol, significantly reducing the impact of external humidity on the contents. At the same time, the three-dimensional structure of long-chain alkyl hydrophobic segments can increase the coating effect with disintegrants, improve the binding force between components, further prevent water from entering the tablet interior, and improve the strength of the tablet, effectively preventing damage during transportation. Furthermore, the amphiphilic structure in the molecular chain improves the compatibility between the modified polyethylene glycol and the contents, which is conducive to the uniform dispersion of components and the formation of a uniform coating structure. This makes the disintegration process more controllable and prolonged, and promotes the full and complete disintegration of the product. Detailed Implementation

[0021] To more clearly illustrate the technical solution of the present invention, the following embodiments are provided. Unless otherwise stated, the raw materials, reactions, and post-processing methods appearing in the embodiments are all commercially available raw materials and technical methods well known to those skilled in the art.

[0022] The terms "preferred," "more preferably," and "more suitable" used in this invention refer to embodiments of the invention that provide certain beneficial effects under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of this invention.

[0023] It should be understood that, except in any operational instance or otherwise indicated, all figures representing the amounts of ingredients used, for example, in the specification and claims, should be understood to be modified in all cases by the term "about". Therefore, unless otherwise stated, the numerical parameters set forth in the following specification and appended claims are approximations varying with the desired performance to be obtained according to the invention.

[0024] Disintegrant, hydroxypropyl cellulose, 191884, purchased from Sigma.

[0025] Lubricant, magnesium stearate.

[0026] A gliding agent, talc.

[0027] Polyethylene glycol 6000 and 81260 were purchased from Sigma.

[0028] Monomethyl ether polyethylene glycol, 2000 Da, purchased from Sigma.

[0029] N,N-carbonyldiimidazole, CDI, purchased from Sigma.

[0030] Example 1 A polyethylene glycol disintegrating tablet, the polyethylene glycol disintegrating tablet comprising the following components in parts by weight: 27 parts sodium carbonate 7 parts modified polyethylene glycol 8 parts disintegrant 1 part lubricant One part of gliding agent; The preparation method of the above-mentioned polyethylene glycol disintegrating tablets includes the following steps: S1. Using methanol as a solvent, n-octylamine and tetradecyl acrylate were mixed and heated to 35°C for 24 hours. The solvent was removed by vacuum distillation to obtain intermediate product 1. The mass ratio of n-octylamine to tetradecyl acrylate is 1:4. S2. Using methanol as a solvent, intermediate product 1 was mixed with ethylenediamine, heated to 35°C and reacted for 24 hours. The solvent was removed by vacuum distillation to obtain intermediate product 2. The mass ratio of intermediate product 1 to ethylenediamine is 2:1; S3. Using tetrahydrofuran as a solvent, monomethyl ether polyethylene glycol and N,N-carbonyl diimidazole were mixed and reacted at room temperature for 24 hours under argon protection. The mixture was then precipitated in anhydrous diethyl ether, filtered, and dried to obtain activated polyethylene glycol. The mass ratio of the monomethyl ether polyethylene glycol to N,N-carbonyl diimidazole is 5:4. S4. Using tetrahydrofuran as a solvent, intermediate product 2 was mixed with activated polyethylene glycol and reacted at room temperature for 24 hours. After removing the solvent and drying, modified polyethylene glycol was obtained. The mass ratio of intermediate product 2 to activated polyethylene glycol is 1:0.8; S5. According to the above-mentioned mass proportions, heat the modified polyethylene glycol to 60°C, then add the contents, mix evenly, then add the remaining components, stir and granulate, mix and compress to obtain the polyethylene glycol disintegrating tablets.

[0031] Example 2 A polyethylene glycol disintegrating tablet, the polyethylene glycol disintegrating tablet comprising the following components in parts by weight: 30 parts sodium bicarbonate 9 parts modified polyethylene glycol 10 parts disintegrant 1 part lubricant One part of gliding agent; The preparation method of the above-mentioned polyethylene glycol disintegrating tablets includes the following steps: S1. Using methanol as a solvent, n-octylamine and hexadecyl acrylate were mixed and heated to 35°C for 24 hours. The solvent was removed by vacuum distillation to obtain intermediate product 1. The mass ratio of n-octylamine to hexadecyl acrylate is 1:4. S2. Using methanol as a solvent, intermediate product 1 was mixed with ethylenediamine, heated to 35°C and reacted for 24 hours. The solvent was removed by vacuum distillation to obtain intermediate product 2. The mass ratio of intermediate product 1 to ethylenediamine is 2:1; S3. Using tetrahydrofuran as a solvent, monomethyl ether polyethylene glycol and N,N-carbonyl diimidazole were mixed and reacted at room temperature for 24 hours under argon protection. The mixture was then precipitated in anhydrous diethyl ether, filtered, and dried to obtain activated polyethylene glycol. The mass ratio of the monomethyl ether polyethylene glycol to N,N-carbonyl diimidazole is 5:4. S4. Using tetrahydrofuran as a solvent, intermediate product 2 was mixed with activated polyethylene glycol and reacted at room temperature for 24 hours. After removing the solvent and drying, modified polyethylene glycol was obtained. The mass ratio of intermediate product 2 to activated polyethylene glycol is 1:0.8; S5. According to the above-mentioned mass proportions, heat the modified polyethylene glycol to 60°C, then add the contents, mix evenly, then add the remaining components, stir and granulate, mix and compress to obtain the polyethylene glycol disintegrating tablets.

[0032] Example 3 A polyethylene glycol disintegrating tablet, the polyethylene glycol disintegrating tablet comprising the following components in parts by weight: 35 parts sodium percarbonate 12 parts modified polyethylene glycol 12 parts of disintegrant 1 part lubricant One part of gliding agent; The preparation method of the above-mentioned polyethylene glycol disintegrating tablets includes the following steps: S1. Using methanol as a solvent, n-octylamine and octadecyl acrylate were mixed and heated to 35°C for 24 hours. The solvent was removed by vacuum distillation to obtain intermediate product 1. The mass ratio of n-octylamine to octadecyl acrylate is 1:4. S2. Using methanol as a solvent, intermediate product 1 was mixed with ethylenediamine, heated to 35°C and reacted for 24 hours. The solvent was removed by vacuum distillation to obtain intermediate product 2. The mass ratio of intermediate product 1 to ethylenediamine is 2:1; S3. Using tetrahydrofuran as a solvent, monomethyl ether polyethylene glycol and N,N-carbonyl diimidazole were mixed and reacted at room temperature for 24 hours under argon protection. The mixture was then precipitated in anhydrous diethyl ether, filtered, and dried to obtain activated polyethylene glycol. The mass ratio of the monomethyl ether polyethylene glycol to N,N-carbonyl diimidazole is 5:4. S4. Using tetrahydrofuran as a solvent, intermediate product 2 was mixed with activated polyethylene glycol and reacted at room temperature for 24 hours. After removing the solvent and drying, modified polyethylene glycol was obtained. The mass ratio of intermediate product 2 to activated polyethylene glycol is 1:0.8; S5. According to the above-mentioned mass proportions, heat the modified polyethylene glycol to 60°C, then add the contents, mix evenly, then add the remaining components, stir and granulate, mix and compress to obtain the polyethylene glycol disintegrating tablets.

[0033] Comparative Example 1 A polyethylene glycol disintegrating tablet, the difference between this comparative example and Example 1 is that in step S1, methacrylate is replaced with tetradecyl acrylate of equal mass, while other components and preparation methods are the same.

[0034] Comparative Example 2 A polyethylene glycol disintegrating tablet, the difference between this comparative example and Example 1 is that steps S1-S4 are removed, and in step S5, the modified polyethylene glycol is replaced with an equal mass of polyethylene glycol 4000. Other components and preparation methods are the same.

[0035] Test Example 1 The performance of the polyethylene glycol disintegrating tablets prepared in Examples 1-3 and Comparative Examples 1-2 was tested.

[0036] Stability test: Seal the polyethylene glycol disintegrating tablets in a transparent container and place them in an environment with a temperature of 30±2℃. After 2 months of constant temperature storage, take them out and observe the phenomenon immediately. If there is no obvious discoloration or other deterioration, the stability is qualified.

[0037] Disintegration time test: Polyethylene glycol disintegrating tablets are added to water and their disintegration time is calculated.

[0038] The test results are shown in Table 1.

[0039] Table 1. Performance test results of polyethylene glycol disintegrating tablets prepared in Examples 1-3 and Comparative Examples 1-2 Table 1 shows that the disintegration tablets of Examples 1-3 all passed the stability test, with no discoloration or clumping, and the disintegration time was normal. Comparative Example 1 had a short disintegration time, but its stability was unsatisfactory and it showed discoloration. Comparative Example 2 also had a short disintegration time, but its stability was unsatisfactory and it showed severe discoloration and deformation. Therefore, the modified polyethylene glycol used in this invention can significantly improve storage stability while maintaining a normal disintegration time.

[0040] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

[0041] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A polyethylene glycol disintegrating tablet, characterized in that, The polyethylene glycol disintegrating tablets comprise the following components in parts by weight: 25-35 contents 6-15 parts of modified polyethylene glycol 7-15 parts disintegrant Additives: 0.5-10 parts; The modified polyethylene glycol is obtained by reacting n-octylamine with long-chain alkyl acrylate, then with ethylenediamine, and finally with activated polyethylene glycol. The activated polyethylene glycol is obtained by reacting monomethyl ether polyethylene glycol with N,N-carbonyl diimidazole.

2. The polyethylene glycol disintegrating tablet according to claim 1, characterized in that, The contents are selected from one or more of sodium carbonate, sodium bicarbonate, sodium percarbonate, and citric acid.

3. The polyethylene glycol disintegrating tablet according to claim 1, characterized in that, The disintegrant is selected from one or more of hydroxypropyl cellulose and microcrystalline cellulose.

4. The polyethylene glycol disintegrating tablet according to claim 1, characterized in that, The long-chain alkyl acrylate is selected from one or more of tetradecyl acrylate, hexadecyl acrylate, and octadecyl acrylate.

5. The polyethylene glycol disintegrating tablet according to claim 1, characterized in that, The additive is selected from one or more of lubricants and flow aids.

6. The method for preparing polyethylene glycol disintegrating tablets according to any one of claims 1-5, characterized in that, The preparation method of the polyethylene glycol disintegrating tablets includes the following steps: S1. Mix n-octylamine with long-chain alkyl acrylate and heat to react, to obtain intermediate product 1; S2. Mix intermediate product 1 with ethylenediamine and heat to react, to obtain intermediate product 2; S3. Mix monomethyl ether polyethylene glycol with N,N-carbonyl diimidazole and react at room temperature under the protection of an inert gas to obtain activated polyethylene glycol; S4. Mix intermediate product 2 with activated polyethylene glycol and react at room temperature to obtain modified polyethylene glycol; S5. Mix the modified polyethylene glycol and the contents, then add the remaining ingredients, stir and granulate, mix and compress to obtain the polyethylene glycol disintegrating tablet.

7. The method for preparing polyethylene glycol disintegrating tablets according to claim 6, characterized in that, In step S1, the heating temperature is 30-40℃; In step S2, the heating temperature is 35-40℃.

8. The method for preparing polyethylene glycol disintegrating tablets according to claim 6, characterized in that, In step S1, the mass ratio of n-octylamine to long-chain alkyl acrylate is 1-2:3-5.

9. The method for preparing polyethylene glycol disintegrating tablets according to claim 6, characterized in that, In step S2, the mass ratio of intermediate product 1 to ethylenediamine is 1-2:0.1-1.

10. The method for preparing polyethylene glycol disintegrating tablets according to claim 6, characterized in that, In step S3, the mass ratio of the monomethyl ether polyethylene glycol to N,N-carbonyl diimidazole is 1-3:1-2; In step S4, the mass ratio of intermediate product 2 to activated polyethylene glycol is 1-2:0.8-1.5.

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