Flash-release excipient, preparation method therefor, and use thereof

Abstract

The present invention belongs to the technical field of food formulations. Disclosed are a flash-release excipient, a preparation method therefor, and use thereof. The flash-release excipient consists of a polyhydric sugar alcohol and starch. According to the present invention, the specific polyhydric sugar alcohol and the specific starch have a synergistic effect, and are compounded in a specific mass ratio; and a wet granulation method comprising low-temperature drying treatment and subsequent high-temperature sterilization is further employed to prepare the flash-release excipient. According to the present invention, the flash-release excipient does not contain any binders and disintegrants, and has a flash-release characteristic of disintegration time of less than two seconds in artificial saliva and water while reducing costs.

Description

A flash-release excipient and its preparation method and application

[0001] Priority claim: The present invention claims priority to Chinese patent application No. 2023116622884 filed on December 6, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0002] The present invention belongs to the technical field of food preparations, and in particular relates to a flash-release excipient and a preparation method and application thereof. Background Art

[0003] Existing granulation methods are broadly categorized into: 1. Wet granulation, which involves adding a binder during granulation; 2. Dry granulation, which involves compressing and pulverizing the powder; 3. Granulation, which involves melting the powder by heating it; and 4. Fluidized bed granulation, which involves spraying a binder solution and compressed air into the fluidized powder. Of these granulation methods, wet or dry granulation is often used for powder processing for ease of operation.

[0004] However, when the product contains a large amount of erythritol, the product obtained by simply using dry granulation or wet granulation cannot achieve the effect of instant dissolution, or the instant dissolution effect is poor. Chinese invention patent CN110313597A discloses a method for making instant, water-free granules by wet granulation, wherein the excipients include: 10-100 parts of sugar alcohol, 20-40 parts of instant fruit powder, 30-100 parts of starch, and 3-10 parts of disintegrant. This patent is a typical example of a better instant dissolution effect in the current patent data, but the oral disintegration speed of this patent is as long as 4 seconds, a disintegrant is added, and the preparation process steps are cumbersome and the cost is high. Chinese invention patent CN112544984A discloses an oral instant dissolution granule, the excipients of which are erythritol, xylitol, sorbitol and / or maltitol, potato starch, corn starch and resistant dextrin. Chinese invention patent CN114098059A discloses an oral fast-dissolving composition for hangover relief and liver protection, as well as its preparation method and preparation equipment. The auxiliary materials include 15-20 parts of sugar alcohol and 1-2 parts of starch. Although it has an instant dissolution effect, the instant dissolution time takes 5 seconds. The various auxiliary materials, adhesives, flavors, etc. added increase the cost and reduce the content of effective substances under the same specifications. CN105030723A discloses a starch capsule and its preparation method. The premixed auxiliary materials are composed of the following ingredients: 30-40 parts of hydroxypropyl starch, 20-30 parts of starch, 1-5 parts of mannitol, 0.5-2 parts of hypromellose, 0.5-5 parts of sorbitol, and 1-4 parts of povidone. The disintegration time of this patent is as short as 5 minutes, and the addition of disintegrants increases the cost.

[0005] Yin Zongmei et al. reported a mannitol-starch composite excipient for direct tableting in Chinese Journal of Pharmaceutical Sciences, 2015(4):348-351. The mannitol-starch composite excipient was prepared by granulation technology with a mass ratio of mannitol to starch of 20:1. The mannitol-starch composite excipient can be used as a carrier for drug loading and has excellent fluidity, compressibility, filling and disintegration properties. The content uniformity of low-dose tablets meets the requirements and is suitable for direct tableting.

[0006] Currently, the instant dissolving products on the market take more than 4 seconds to dissolve in artificial saliva or water, and the existing instant dissolving process is complex and costly. The pre-made excipients in the existing technology take a long time to dissolve. Therefore, there is an urgent need to develop a flash-release excipient that is low-cost, simple to process, and dissolves quickly.

[0007] Summary of the Invention

[0008] In order to solve the technical problems of high cost, complex preparation process and poor instant dissolution effect of instant products and prefabricated excipients in the prior art, the purpose of the present invention is to provide a flash-release excipient and its preparation method and application.

[0009] In order to achieve the above object, the present invention adopts the following technical solutions:

[0010] The invention provides a flash-release excipient consisting of polyols and starch.

[0011] Furthermore, the mass ratio of the starch to the polyol is 1:0.5-1.5.

[0012] Furthermore, the mass ratio of the starch to the polyol is 1:0.8-1.5.

[0013] Furthermore, the mass ratio of the starch to the polyol is 1:1.

[0014] Furthermore, the polyol is at least one of erythritol, xylitol and sorbitol.

[0015] Furthermore, the polyol is erythritol.

[0016] Furthermore, the starch is at least one of potato starch and corn starch.

[0017] Furthermore, the flash-release excipient is composed of 40-60 parts of polyols and 40-60 parts of starch by weight.

[0018] The present invention also provides a method for preparing the flash-release excipient, comprising the following steps:

[0019] The polyol and starch are weighed according to the formula, mixed, granulated, and the whole granules are dried to obtain a flash-release excipient.

[0020] Furthermore, the granulation is wet granulation.

[0021] Furthermore, in the wet granulation, the stirring speed is 100-300 rpm, the cutter speed is 1000-2500 rpm, the water addition amount is 5wt%-12.5wt%, the water inlet rate is 200-400 rpm, and the temperature is 20-25°C.

[0022] Furthermore, the drying is: drying at 40-50° C. for 0.5-1.5 hours.

[0023] The present invention also provides application of the flash-release excipient in the preparation of flash-release health-care products, foods and medicines.

[0024] A flash-release product comprising the above-mentioned flash-release excipient.

[0025] Furthermore, the dosage form of the flash-release product is granules or microcapsules, pills, powders or tablets.

[0026] Polysaccharide alcohols are prone to recrystallization. If directly mixed with other materials for wet granulation and then dried, the finished product will have a distinctly granular feel and be difficult to disintegrate in artificial saliva, failing to achieve instant dissolution. Starch is a water-soluble material. By encapsulating the polysaccharide alcohol with starch to form a dispersed structure, the resulting granules exhibit instant dissolution. This ensures solubility during subsequent granulation with other products. Because it is a water-soluble material, its release rate in artificial saliva is less than two seconds, resulting in a flash-release effect.

[0027] Starch is insoluble in water and has hydroscopic properties. During the wet granulation process, it absorbs water and combines with sugar alcohol to form an inclusion compound. During the drying process, the moisture content is reduced, making the small particle group structure tighter and the particles more dispersed, preventing the sugar alcohol from recrystallizing and ensuring the dissolution rate.

[0028] It avoids the recrystallization of polyols, which affects the dissolution of subsequent products and causes granular taste. At the same time, low-temperature drying can prevent the gelatinization properties of starch from changing and affecting the yield rate.

[0029] The beneficial effects of the present invention are:

[0030] The flash-release excipient of the present invention is compounded with a specific polyol and a specific starch to achieve synergistic effects and is compounded in a specific mass ratio. A low-temperature drying method is further adopted to reduce the moisture content of the starch to below the gelatinization moisture content, thereby ensuring that the starch does not undergo gelatinization reaction during high-temperature sterilization and maintains its original high water absorption, thereby maintaining the flash-release characteristics with the flash-release excipient composed of erythritol.

[0031] During the granulation process, the higher the proportion of the present invention added, the better the solubility of the finished granule, the faster the disintegration rate, and the shorter the disintegration time. The main function of the present invention is to act as a filler with good solubility, and even after adding other active ingredients, the granulation still has flash release characteristics. Moreover, the present invention does not add disintegrants, binders, or other additives, ensuring that the present invention and the active ingredients or other raw materials are unlikely to react and affect the efficacy of the components. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] FIG1 is the morphology of the flash-release excipient of Example 1;

[0033] FIG2 is the morphology of the flash-release excipient of Comparative Example 9. DETAILED DESCRIPTION

[0034] The following describes the embodiments of the present invention through specific examples. Those skilled in the art will readily understand the other advantages and benefits of the present invention from the disclosure herein. The present invention may also be implemented or applied through various other specific embodiments, and the details in this specification may be modified or altered based on different viewpoints and applications without departing from the spirit of the present invention.

[0035] Before further describing the specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the examples of the present invention are for describing specific embodiments rather than for limiting the scope of protection of the present invention.

[0036] When numerical ranges are given in the examples, it should be understood that, unless otherwise specified herein, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention belongs.

[0037] The present invention does not limit the sources of the raw materials used. Unless otherwise specified, the raw materials used in the present invention are common commercial products in the technical field.

[0038] Basic Example

[0039] Example 1

[0040] A flash-release excipient consists of 45 parts of erythritol and 45 parts of potato starch, calculated by weight.

[0041] The preparation method of the flash-release excipient comprises the following steps:

[0042] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator with stirring. The wet granulator parameters were as follows: stirring speed 200 rpm, cutter speed 2000 rpm, water addition amount 5.5 wt%, water inflow rate 200 rpm, and temperature 25°C. After stirring, the mixture was added to a granulator for granulation. After granulation, the granules were dried at 40°C for 0.5 h to produce a flash-release excipient.

[0043] Example 2

[0044] A flash-release excipient consists of 55 parts of erythritol and 50 parts of potato starch, calculated by weight.

[0045] The preparation method of the flash-release excipient comprises the following steps:

[0046] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator with stirring. The wet granulator parameters were as follows: stirring speed 200 rpm, cutter speed 2000 rpm, water addition amount 5.5 wt %, water inflow rate 200 rpm, and temperature 25°C. After stirring, the mixture was added to a granulator for granulation. After granulation, the granules were dried at 50°C for 1.5 hours to produce a flash-release excipient.

[0047] Example 3

[0048] A flash-release excipient consists of 40 parts of xylitol and 60 parts of potato starch in parts by weight.

[0049] The preparation method of the flash-release excipient comprises the following steps:

[0050] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator with stirring. The wet granulator parameters were as follows: stirring speed 250 rpm, cutter speed 1500 rpm, water addition amount 7.5 wt %, water inflow rate 300 rpm, and temperature 20°C. After stirring, the mixture was added to a granulator for granulation. After granulation, the granules were dried at 50°C for 1.5 hours to produce a flash-release excipient.

[0051] Example 4

[0052] A flash-release excipient consists of 45 parts of erythritol and 50 parts of corn starch, calculated by weight.

[0053] The preparation method of the flash-release excipient comprises the following steps:

[0054] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator with stirring. The wet granulator parameters were as follows: stirring speed 100 rpm, cutter speed 1500 rpm, water addition amount 12.5 wt %, water inflow rate 300 rpm, and temperature 20°C. After stirring, the mixture was added to a granulator for granulation. After granulation, the granules were dried at 45°C for 1 hour to produce the flash-release excipient.

[0055] Example 5

[0056] A flash-release excipient consists of 50 parts of sorbitol and 40 parts of corn starch in parts by weight.

[0057] The preparation method of the flash-release excipient comprises the following steps:

[0058] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator with stirring. The wet granulator parameters were as follows: stirring speed 250 rpm, cutter speed 1500 rpm, water addition amount 6.5 wt%, water inflow rate 300 rpm, and temperature 20°C. After stirring, the mixture was added to a granulator for granulation. After granulation, the granules were dried at 45°C for 1 hour to produce the flash-release excipient.

[0059] Example 6

[0060] A flash-release excipient consists of 60 parts of erythritol and 40 parts of potato starch, calculated by weight.

[0061] The preparation method of the flash-release excipient comprises the following steps:

[0062] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator with stirring. The wet granulator parameters were as follows: stirring speed 200 rpm, cutter speed 2000 rpm, water addition amount 7.5 wt%, water inflow rate 200 rpm, temperature 25°C. After stirring, the mixture was added to a granulator for granulation. After granulation, the granules were dried at 40°C for 0.5 h to produce a flash-release excipient.

[0063] Basic comparative example

[0064] Comparative Example 1

[0065] The difference between this comparative example and Example 1 is that potato starch is not used.

[0066] Comparative Example 2

[0067] The difference between this comparative example and Example 1 is that erythritol is not used.

[0068] Comparative Example 3

[0069] The difference between this comparative example and Example 1 is that the weight ratio of potato starch to erythritol is different; specifically, the weight ratio of potato starch to erythritol is 1:2, wherein the weight parts of potato starch are 30 parts and the weight parts of erythritol are 60 parts.

[0070] Comparative Example 4

[0071] This comparative example differs from Example 1 in that the weight ratio of potato starch to erythritol is different; specifically, the weight ratio of potato starch to erythritol is 1:0.4, with 60 parts by weight of potato starch and 24 parts by weight of erythritol. During the wet granulation process, the amount of water added was increased to 13%, and the drying time in step S1 was extended to 3 hours.

[0072] Comparative Example 5

[0073] The difference between this comparative example and Example 1 is that 45 parts by weight of tapioca starch are used instead of 45 parts by weight of potato starch.

[0074] Comparative Example 6

[0075] The difference between this comparative example and Example 1 is that 45 parts by weight of wheat starch are used instead of 45 parts by weight of potato starch.

[0076] Comparative Example 7

[0077] The difference between this comparative example and Example 1 is that 45 parts by weight of maltitol are used instead of 45 parts by weight of erythritol.

[0078] Comparative Example 8

[0079] The difference between this comparative example and Example 1 is that 45 parts by weight of mannitol are used instead of 45 parts by weight of erythritol.

[0080] Comparative Example 9

[0081] The difference between this comparative example and Example 1 is that the wet granulation process is different. Specifically, the drying in step S1 is performed at 60° C. for 0.5 hours.

[0082] Comparative Example 10

[0083] The difference between this comparative example and Example 1 is that the wet granulation process is different. Specifically, in the wet granulation process, the amount of water added in step S1 is 13 wt %.

[0084] Comparative Example 11

[0085] The difference between this comparative example and Example 1 is that the wet granulation process is different. Specifically, in the wet granulation process, the amount of water added in step S1 is 20 wt %.

[0086] Comparative Example 12

[0087] The difference between this comparative example and Example 1 is that the wet granulation process is different. Specifically, in the wet granulation process, granulation is not performed after granulation, and the granulation is directly dried.

[0088] Comparative Example 13

[0089] The difference between this comparative example and Example 1 is that 40 parts by weight of potato starch, 70 parts by weight of sorbitol, and 10 parts by weight of mannitol used in Example 1 of CN110313597A are used instead of 45 parts by weight of potato starch and 45 parts by weight of erythritol.

[0090] Comparative Example 14

[0091] Jin Xiaocao Throat Soothing Treasures were purchased from Shanghai Jianshun Biotechnology Co., Ltd., product standard code Q / HSHLY 0001S, product patent number ZL201711013148.9.

[0092] Effect Examples

[0093] The flash-release excipients obtained in Basic Examples 1-5 and Comparative Examples 1-13 were respectively mixed with 3.25 parts of a traditional Chinese medicine component, 3.5 parts of a sweetener, 1 part of anhydrous citric acid, and 1.5 parts of menthol, and stirred in a wet granulator. The wet granulator parameters were as follows: stirring speed 200 rpm, cutter speed 2000 rpm, water addition amount 12.5 wt %, water inflow rate 200 rpm, and temperature 25°C. The stirred materials were added to a granulator for granulation. After granulation, the granules were dried at 45°C for 1 hour, then heated to 85°C and dried for 0.5 hour to obtain Effect Examples 1-5 and Effect Comparative Examples 1-13.

[0094] Effect performance test

[0095] Evaluation of the physicochemical properties of flash-release excipients

[0096] 1. Experimental Methods

[0097] 1.1 Dissolution time evaluation

[0098] Examples 1-5 and Comparative Examples 1-14 were evaluated using dissolution time (in artificial saliva and in water at room temperature) as an indicator.

[0099] 1.2 Morphology of flash-release excipients

[0100] The morphology of the flash-release excipients of Example 1 and Comparative Example 9 was observed using an electron microscope.

[0101] 1.3 Formability evaluation

[0102] Examples 1-5 and Comparative Examples 1-12 were evaluated based on their moldability.

[0103] 1.4 Comprehensive Evaluation

[0104] Effective Examples 1-5, Effective Comparative Examples 1-13, and Comparative Example 14 were evaluated based on three indicators: solubility (in artificial saliva), solubility (in water at room temperature), and mouthfeel.

[0105] 2. Experimental Results

[0106] 2.1 Dissolution time evaluation

[0107] The results of dissolution time for Examples 1-5 and Comparative Examples 1-14 are shown in Table 1. As can be seen from the table, the instant dissolution effect of the embodiments is good, and the dissolution time in artificial saliva is between 1.36s and 1.63s. Example 1 only takes 1.36s to dissolve in artificial saliva; the embodiments have a good dissolution effect in normal temperature water, quickly disperse in water, and dissolve quickly after stirring, taking less than 2s. During the drying process of Comparative Example 9, the starch gelatinized and was almost impossible to shape. Too much water was added in Comparative Example 11, causing the starch to form a non-Newtonian fluid state, and granulation could not be shaped. Among them, the dissolution time in artificial saliva of Comparative Example 1 was the longest, which was 22.15s. Comparative Example 1, Comparative Examples 3-6, and Comparative Example 14 did not dissolve well in normal temperature water, and there was still granules at the bottom of the beaker after stirring.

[0108] Table 1

[0109] 2.2 Morphology of flash-release excipients

[0110] Figures 1 and 2 show the morphologies of the flash-release excipients of Example 1 and Comparative Example 9, respectively. Figure 1 shows that the flash-release excipient of Example 1 is virtually intact and coated with a water-soluble material. Figure 2 shows that the flash-release excipient of Comparative Example 9, prepared after direct high-temperature drying and gelatinization, is coated with a water-soluble material, but its molecular structure is disrupted.

[0111] 2.3 Formability evaluation

[0112] The formulation moldability of Examples 1-5 and Comparative Examples 1-12 was evaluated, and the results are shown in Table 2. As can be seen from the results in Table 2, Examples 1-5 and Comparative Examples 5-8 had good molding effects. However, Comparative Examples 1-4 and Comparative Example 10 had poor molding effects, and Comparative Examples 9 and 11 could not be molded. Among them, when the erythritol mass ratio in Comparative Example 3 was too high, the mixture could not be guaranteed to be in a uniformly dispersed state, resulting in an increase in the contact area between erythritol molecules during the wet drying process and an increase in the crystallization rate. In Comparative Example 4, the starch mass ratio was too high, and the amount of water added needed to be increased during wet granulation, resulting in the drying time having to be extended in subsequent steps, and a gelatinized and unmolded state was easily generated in Step S2. Comparative Example 9 experienced starch gelatinization during the drying process, making it impossible to mold. Comparative Example 11 added too much water, causing the starch to form a non-Newtonian fluid state, making granulation impossible. The granulation process can ensure the uniformity and dispersibility of the material, but Comparative Example 12 did not undergo granulation, resulting in a decrease in drying efficiency and a longer process time than other examples.

[0113] Table 2

[0114] 2.4 Comprehensive Evaluation

[0115] The evaluation results of solubility (in artificial saliva), solubility (in normal temperature water), and mouthfeel are shown in Table 3. It can be seen from the table that the flash-release excipient with good solubility of the present invention still has the flash-release characteristic after adding other active ingredients and granulating, and the flash-release effect of the embodiment is good. However, Comparative Example 14 does not have the flash-release effect, and the dissolution time in artificial saliva is 7.25s. After stirring in normal temperature water, there is still powder residue. Comparative Examples 1-8 have a granular or pasty feeling after entering the mouth due to changes in starch composition and content, or due to changes in sugar alcohol composition and content.

[0116] Table 3

[0117] 3. Conclusion

[0118] The flash-release excipient of the present invention is scientifically compounded with a specific polyol and a specific starch, which are premixed in a specific mass ratio and further dried at low temperature to reduce the moisture content of the starch to below the gelatinization moisture content, thereby ensuring that the starch does not undergo gelatinization reaction during high-temperature sterilization and maintains its original high water absorption, thereby maintaining the flash-release characteristics with the flash-release excipient composed of erythritol.

[0119] The present invention is a flash-release excipient with good solubility. After adding other active ingredients and granulating, it still has the flash-release property. In addition, the present invention does not add disintegrants, adhesives and other additives, ensuring that the present invention and the active ingredients or other raw materials are not likely to react and affect the component effects.

[0120] The above further describes the present invention in conjunction with specific embodiments. However, these embodiments are merely exemplary and do not constitute any limitation on the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the technical solutions of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, and such modifications and replacements shall fall within the scope of protection of the present invention.

Claims

1. A flash-release excipient, characterized in that: The invention is composed of polyols and starch; the mass ratio of the starch to the polyols is 1:0.5-1.

5.

2. The flash release excipient according to claim 1, characterized in that The polyol is at least one of erythritol, xylitol and sorbitol; and the starch is potato starch and / or corn starch.

3. The flash release excipient according to claim 1, characterized in that By weight, it consists of 40-60 parts of polysaccharide alcohol and 40-60 parts of starch.

4. The flash release excipient according to claim 1, characterized in that The mass ratio of starch to polyol is 1:0.8-1.

5.

5. The method for preparing the flash-release excipient according to any one of claims 1 to 4, characterized in that: The following steps are involved: The polyol and starch are weighed according to the formula amount, mixed, granulated, granulated, and dried to obtain the flash-release excipient.

6. The preparation method according to claim 5, characterized in that: The granulation is wet granulation.

7. The preparation method according to claim 6, characterized in that: The wet granulation has a stirring speed of 100-300 rpm, a cutting speed of 1000-2500 rpm, a water addition amount of 5 wt%-12.5 wt%, a water inlet rate of 200-400 rpm, and a temperature of 20-25°C; The drying step is: drying at 40-50° C. for 0.5-1.5 h.

8. Use of the flash-release excipient according to any one of claims 1 to 4 or the flash-release excipient prepared by the preparation method according to any one of claims 5 to 7 in the preparation of flash-release health products, foods and medicines.

9. A flash-release product, characterized in that: The invention relates to a flash-release excipient comprising the flash-release excipient described in any one of claims 1 to 4 or the flash-release excipient prepared by the preparation method described in any one of claims 5 to 7.

10. The flash-release product according to claim 9, characterized in that: The dosage form of the flash-release product is granules, microcapsules, pills, powders or tablets.

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