A flash-release excipient and its preparation method and application

Abstract

The present invention belongs to the technical field of food preparations, and discloses a flash-release excipient, a preparation method thereof, and an application thereof. The flash-release excipient is composed of a polyol and starch. The present invention uses a specific polyol and a specific starch to synergistically enhance the effect and compound them in a specific mass ratio; and further adopts a wet granulation method of first low-temperature drying and then high-temperature sterilization to prepare the flash-release excipient. The present invention does not contain any adhesives and disintegrants, and while reducing costs, has a flash-release characteristic of a disintegration time of less than two seconds in artificial saliva and water.

Description

Technical Field

[0001] The invention belongs to the technical field of food preparations, and in particular relates to a flash-release auxiliary material and a preparation method and application thereof. Background Art

[0002] Existing granulation methods are roughly divided into ① wet granulation in which a binder is added during granulation, ② dry granulation in which the powder is compressed and then crushed, ③ granulation by heating and melting the powder, and ④ fluidized bed granulation in which a binder solution and compressed air are sprayed into the fluidized powder. Among the above granulation methods, wet granulation or dry granulation is usually used to process the powdered object for ease of operation.

[0003] However, when the product contains a large amount of erythritol, the product after dry granulation and wet granulation alone cannot achieve the effect of instant dissolution, or the instant dissolution effect is poor. Chinese invention patent CN110313597A discloses a method for making instant granules without watering by wet granulation, wherein the auxiliary materials 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 the best instant dissolution effect in the current patent data, but the oral disintegration speed of this patent is as long as 4 seconds, disintegrants are added, and the preparation process steps are cumbersome and the cost is high. Chinese invention patent CN112544984A discloses an oral instant granule, the auxiliary materials of which are erythritol, xylitol, sorbitol and / or maltitol, potato starch, corn starch and resistant dextrin. Chinese invention patent CN114098059A discloses an oral instant composition for sobering up and protecting the liver, and its preparation method and preparation equipment, wherein the auxiliary materials include 15-20 parts of sugar alcohol and 1-2 parts of starch. Although it has an instant dissolving effect, the instant dissolving time takes 5 seconds, and 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, and 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 hydroxypropyl methylcellulose, 0.5-5 parts of sorbitol, and 1-4 parts of povidone. The shortest disintegration time of this patent is 5 minutes, and the addition of disintegrants increases the cost.

[0004] Yin Zongmei et al. reported a mannitol-starch composite excipient for direct tableting in Chinese Pharmaceutical Journal, 2015(4):348-351. The mannitol-starch composite excipient was prepared by granulation technology with a mannitol: starch mass ratio of 20:1. The mannitol-starch composite excipient can be used as a carrier for loading drugs and has excellent fluidity, compressibility, filling and disintegration. The content uniformity of low-dose tablets meets the requirements and is suitable for direct tableting process.

[0005] The instant products currently on the market take more than 4 seconds to dissolve in artificial saliva or water, and the existing instant dissolution process is relatively complex and costly. The prefabricated excipients in the prior art take a long time to dissolve, so there is an urgent need to develop a flash-release excipient that is low in cost, simple in process, and quickly dissolves. Summary of the invention

[0006] 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 object of the present invention is to provide a flash-release excipient and a preparation method and application thereof.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] The invention provides a flash-release auxiliary material, which consists of polyol and starch.

[0009] Furthermore, the mass ratio of the starch to the polyol is 1:0.5-1.5.

[0010] Furthermore, the mass ratio of the starch to the polyol is 1:0.8-1.5.

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

[0012] Furthermore, the polyol is at least one of erythritol, xylitol and sorbitol.

[0013] Furthermore, the polyol is erythritol.

[0014] Furthermore, the starch is at least one of potato starch and corn starch.

[0015] Furthermore, the flash-release excipients are composed of 40-60 parts of polysaccharide alcohol and 40-60 parts of starch by weight.

[0016] The present invention also provides a method for preparing the flash-release excipient, comprising the following steps:

[0017] The polyol and starch are weighed according to the formula amount, mixed, granulated, and the whole granules are dried to obtain the flash-release excipient.

[0018] Furthermore, the granulation is wet granulation.

[0019] Furthermore, in the wet granulation, the stirring speed is 100-300rpm, the cutting speed is 1000-2500rpm, the water addition amount is 5wt%-12.5wt%, the water inlet rate is 200-400rpm, and the temperature is 20-25°C.

[0020] Furthermore, the drying is: drying at 40-50° C. for 0.5-1.5 h.

[0021] The present invention also provides application of the flash-release auxiliary material in the preparation of flash-release health products, foods and medicines.

[0022] A flash-release product comprises the above-mentioned flash-release excipient.

[0023] Furthermore, the dosage form of the flash-release product is granules or microcapsules, pills, powders or tablets.

[0024] Polysaccharide alcohols are easy to recrystallize. If they are directly mixed with other materials for wet granulation and then dried, the finished product will have obvious granular feeling and will be difficult to disintegrate in artificial saliva, and will not achieve the effect of instant dissolution. Starch is a water-soluble material. By making starch encapsulate polysaccharide alcohols to form a dispersed structure, the obtained particles have an instant dissolution effect. Solubility can still be guaranteed in the subsequent granulation process with other products. Since it is a water-soluble material, the release rate in artificial saliva is less than two seconds, which has a flash release effect.

[0025] Starch is easily soluble 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.

[0026] It avoids the recrystallization of polyols, which may affect the dissolution of subsequent products and cause granular taste. At the same time, low-temperature drying can prevent the gelatinization properties of starch from changing and affecting the yield.

[0027] The beneficial effects of the present invention are:

[0028] The flash-release auxiliary material of the present invention is compounded with a specific polyol and a specific starch to synergistically enhance the effect and is compounded in a specific mass ratio; and further adopts a low-temperature drying method to reduce the moisture content of the starch to below the gelatinization moisture content, thereby ensuring that the starch does not undergo gelatinization reaction when sterilized at high temperature, maintaining the original high water absorption, thereby maintaining the flash-release characteristics with the flash-release auxiliary material composed of erythritol.

[0029] In the granulation process of granules, the higher the proportion of the present invention is added, the better the solubility of the granulated product, the faster the disintegration speed, and the shorter the disintegration time. The main function of the present invention is to be a filler with good solubility and still have flash release characteristics after adding other active ingredients for granulation, and the present invention does not add disintegrants, binders and other additives, ensuring that the present invention and the active ingredients or other raw materials are not easy to react and affect the component effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is the morphology of the flash-release excipient of Example 1;

[0031] Figure 2 This is the morphology of the flash-release excipient of Comparative Example 9. DETAILED DESCRIPTION

[0032] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0033] 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.

[0034] When the embodiment gives a numerical range, it should be understood that, unless otherwise specified in the present invention, the two endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those of ordinary skill in the art to which the present invention belongs.

[0035] 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.

[0036] Basic Example

[0037] Example 1

[0038] A flash-release auxiliary material consists of 45 parts of erythritol and 45 parts of potato starch by weight.

[0039] The preparation method of the flash-release excipient comprises the following steps:

[0040] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator for stirring. The parameters of the wet granulator were as follows: stirring speed 200 rpm, cutting knife speed 2000 rpm, water addition amount 5.5 wt%, water inlet rate 200 rpm, temperature 25° C. After stirring, the material was added to a granulator for granulation, and then dried at 40° C. for 0.5 h to obtain a flash release excipient.

[0041] Example 2

[0042] A flash-release auxiliary material consists of 55 parts of erythritol and 50 parts of potato starch by weight.

[0043] The preparation method of the flash-release excipient comprises the following steps:

[0044] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator for stirring. The parameters of the wet granulator were as follows: stirring speed 200 rpm, cutting knife speed 2000 rpm, water addition amount 5.5 wt%, water inlet rate 200 rpm, temperature 25° C. After stirring, the material was added to a granulator for granulation, and then dried at 50° C. for 1.5 h to obtain a flash release excipient.

[0045] Example 3

[0046] A flash-release auxiliary material consists of 40 parts of xylitol and 60 parts of potato starch by weight.

[0047] The preparation method of the flash-release excipient comprises the following steps:

[0048] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator for stirring. The parameters of the wet granulator were as follows: stirring speed 250 rpm, cutting knife speed 1500 rpm, water addition amount 7.5 wt%, water inlet rate 300 rpm, temperature 20° C. After stirring, the material was added to a granulator for granulation, and then dried at 50° C. for 1.5 h to obtain a flash release excipient.

[0049] Example 4

[0050] A flash-release auxiliary material consists of 45 parts of erythritol and 50 parts of corn starch by weight.

[0051] The preparation method of the flash-release excipient comprises the following steps:

[0052] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator for stirring. The parameters of the wet granulator were as follows: stirring speed 100 rpm, cutting knife speed 1500 rpm, water addition amount 12.5 wt%, water inlet rate 300 rpm, temperature 20° C. After stirring, the material was added to a granulator for granulation, and then dried at 45° C. for 1 h to obtain a flash release excipient.

[0053] Example 5

[0054] A flash-release auxiliary material consists of 50 parts of sorbitol and 40 parts of corn starch by weight.

[0055] The preparation method of the flash-release excipient comprises the following steps:

[0056] The polyol and starch were weighed according to the formula, mixed, and added to a wet granulator for stirring. The parameters of the wet granulator were as follows: stirring speed 250 rpm, cutting knife speed 1500 rpm, water addition amount 6.5 wt%, water inlet rate 300 rpm, temperature 20° C. After stirring, the material was added to a granulator for granulation, and then dried at 45° C. for 1 h to obtain a flash release excipient.

[0057] Basic comparison

[0058] Comparative Example 1

[0059] The difference between this comparative example and Example 1 is that potato starch is not used.

[0060] Comparative Example 2

[0061] The difference between this comparative example and Example 1 is that erythritol is not used.

[0062] Comparative Example 3

[0063] 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 portion of potato starch is 30 parts, and the weight portion of erythritol is 60 parts.

[0064] Comparative Example 4

[0065] 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 1:0.4, wherein the weight portion of potato starch is 60 parts and the weight portion of erythritol is 24 parts. During the wet granulation process, the amount of water added is increased to 13%, and the drying time in step S1 is extended to 3 hours.

[0066] Comparative Example 5

[0067] 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.

[0068] Comparative Example 6

[0069] 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.

[0070] Comparative Example 7

[0071] 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.

[0072] Comparative Example 8

[0073] 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.

[0074] Comparative Example 9

[0075] 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 hour.

[0076] Comparative Example 10

[0077] 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 %.

[0078] Comparative Example 11

[0079] 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 %.

[0080] Comparative Example 12

[0081] 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 granulation is directly dried.

[0082] Comparative Example 13

[0083] 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.

[0084] Comparative Example 14

[0085] Jin Xiaocao Throat Soaking Treasures were purchased from Shanghai Jianshun Biotechnology Co., Ltd., product standard code Q / HSHLY 0001S, product patent number ZL201711013148.9.

[0086] Effect example

[0087] The flash-release excipients obtained in basic examples 1-5 and comparative examples 1-13 were respectively mixed with 3.25 parts of Chinese medicinal ingredients, 3.5 parts of sweeteners, 1 part of anhydrous citric acid and 1.5 parts of menthol, and placed in a wet granulator for stirring. The parameters of the wet granulator were as follows: stirring speed 200 rpm, cutting knife speed 2000 rpm, water addition amount 12.5 wt%, water inlet rate 200 rpm, temperature 25° C. After stirring, the materials were added to a granulator for granulation. After granulation, the granules were dried at 45° C. for 1 hour, and then heated to 85° C. for drying for 0.5 hours to obtain effect examples 1-5 and effect comparative examples 1-13.

[0088] Evaluation of the physicochemical properties of flash-release excipients in efficacy performance tests

[0089] 1. Experimental Methods

[0090] 1.1 Evaluation of dissolution time

[0091] Examples 1-5 and Comparative Examples 1-14 were evaluated using the dissolution time (in artificial saliva and in water at room temperature) as an indicator.

[0092] 1.2 Morphology of flash-release excipients

[0093] The morphology of the flash-release excipients of Example 1 and Comparative Example 9 was observed using an electron microscope.

[0094] 1.3 Formability evaluation

[0095] Examples 1-5 and Comparative Examples 1-12 were evaluated on the basis of their formability.

[0096] 1.4 Comprehensive evaluation

[0097] Effect Examples 1-5, Effect Comparative Examples 1-13, and Comparative Example 14 were evaluated based on three indicators: solubility (dissolution in artificial saliva), solubility (in water at room temperature), and mouthfeel.

[0098] 2. Experimental results

[0099] 2.1 Evaluation of dissolution time

[0100] The results of dissolution time for Examples 1-5 and Comparative Examples 1-14 are shown in Table 1. It can be seen from the table that the instant dissolution effect of the embodiments is good, and the dissolution time in artificial saliva is between 1.36s and 1.63s, and Example 1 only takes 1.36s to dissolve in artificial saliva; the embodiments have good dissolution effect in water at room temperature, 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 form. Too much water was added in Comparative Example 11, causing the starch to form a non-Newtonian fluid state, and granulation could not be formed. 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 water at room temperature, and there was still granules at the bottom of the beaker after stirring.

[0101] Table 1

[0102]

[0103] 2.2 Morphology of flash-release excipients

[0104] Figure 1 and Figure 2 The morphologies of the flash-release excipients of Example 1 and Comparative Example 9 are shown respectively. Figure 1 It can be seen that in Example 1, the flash-release excipient is almost intact and is wrapped by a water-soluble material. Figure 2 It can be seen that in Comparative Example 9, the flash-release excipient prepared after direct high-temperature drying and gelatinization is wrapped by a water-soluble material, but its molecular structure has been destroyed.

[0105] 2.3 Formability evaluation

[0106] The formulation molding properties of Examples 1-5 and Comparative Examples 1-12 were evaluated, and the results are shown in Table 2. As can be seen from the results in Table 2, the molding effects of Examples 1-5 and Comparative Examples 5-8 are good. However, the molding properties of Comparative Examples 1-4 and Comparative Example 10 are not good, and Comparative Examples 9 and Comparative Example 11 cannot be molded. Among them, when the mass ratio of erythritol in Comparative Example 3 is too high, the mixture cannot ensure a uniformly dispersed state, resulting in an increase in the contact area between erythritol molecules during wet drying and an increase in the crystallization rate. In Comparative Example 4, the mass ratio of starch is too high, and the amount of water added needs to be increased during wet granulation, resulting in the need to extend the drying time in subsequent steps, and gelatinization and non-molding state are prone to occur in step S2. Starch gelatinization occurs in Comparative Example 9 during the drying process and cannot be molded. Excessive water addition in Comparative Example 11 causes starch to form a non-Newtonian fluid state, and granulation cannot be molded. The granulation process can ensure the uniformity and dispersibility of the material. Comparative Example 12 is not granulated, resulting in a decrease in drying efficiency and a longer process time than other embodiments.

[0107] Table 2

[0108]

[0109] 2.4 Comprehensive Evaluation

[0110] The evaluation results of solubility (in artificial saliva), solubility (in water at room temperature), 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. There is still powder residue after stirring in water at room temperature. Comparative Examples 1-8 have a granular or pasty feeling after entering the mouth due to changes in starch composition and content, or changes in sugar alcohol composition and content.

[0111] Table 3

[0112]

[0113]

[0114]

[0115] 3. Conclusion

[0116] The flash-release auxiliary material of the present invention is scientifically compounded with specific polysaccharide alcohols and specific starches, 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 maintaining its original high water absorption, thereby maintaining the flash-release characteristics with the flash-release auxiliary material composed of erythritol.

[0117] The present invention is a flash-release excipient with good solubility and still has flash-release characteristics after adding other active ingredients for granulation. The present invention does not add disintegrants, adhesives and other additives, ensuring that the present invention and the effective ingredients or other raw materials are not easy to react and affect the component effects.

[0118] The above is a further description of the present invention in conjunction with specific embodiments, but 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 solution of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, but these modifications and replacements all fall within the scope of protection of the present invention.

Claims

1. A flash-release excipient, characterized in that: Made from polyols and starch; The mass ratio of the starch to the polyol is 1:0.8-1.5; The polyol is one of erythritol, xylitol and sorbitol; The starch is potato starch or corn starch; The preparation method of the flash-release excipient comprises: weighing polyol and starch according to the formula amount, mixing, wet granulating, granulating, and drying to obtain the flash-release excipient; In the wet granulation, the amount of water added is 5wt%-12.5wt%; The drying step is: drying at 40-50°C for 0.5-1.5 h.

2. 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.

3. The method for preparing the flash-release excipient according to any one of claims 1 to 2, characterized in that: The method comprises the following steps: weighing polyols and starch according to the formula amount, mixing, wet granulating, granulating, and drying to obtain flash-release auxiliary materials.

4. The preparation method according to claim 3, 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 5wt%-12.5wt%, a water inlet rate of 200-400 rpm, and a temperature of 20-25°C.

5. Use of the flash-release excipient according to any one of claims 1 to 2 or the flash-release excipient prepared by the preparation method according to any one of claims 3 to 4 in the preparation of flash-release health products, foods and medicines.

6. 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 2 or the flash-release excipient prepared by the preparation method described in any one of claims 3 to 4.

7. The flash-release product according to claim 6, characterized in that: The dosage form of the flash-release product is granules, microcapsules, pills, powders or tablets.

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