L-carnitine composite tablet with high hygroscopicity resistance and preparation method of L-carnitine composite tablet

Abstract

The invention discloses an L-carnitine composite tablet with high hygroscopicity resistance and a preparation method of the L-carnitine composite tablet. The preparation method comprises the following steps: S1, adding 65-80 parts by weight of dietary fiber, 1-3 parts by weight of tea polyphenol, 5-10 parts by weight of isomaltitol, 1-3 parts by weight of calcium carbonate and 0.75-1.5 parts by weight of hydroxypropyl methylcellulose into a boiling drying granulator, and mixing to obtain mixed powder; s2, uniformly spraying a citric acid solution on the surface of the mixed powder in a guniting manner to obtain a first guniting material; s3, uniformly spraying an L-carnitine solution on the surface of the first guniting material in a guniting manner, so that L-carnitine is uniformly absorbed in pores of dietary fibers and honeycomb-shaped pores generated by citric acid and calcium carbonate to obtain a second guniting material; and S4, carrying out guniting granulation by utilizing 0.25-0.5 part of a hydroxypropyl methylcellulose solution, adding 2-3 parts by weight of a lubricant and an anti-caking agent after granulation is completed, uniformly mixing to obtain a total mixed material, tabletting, and coating to obtain the L-carnitine composite tablet.

Description

Technical Field

[0001] The present invention relates to the technical field of food processing, and more specifically to a L-carnitine composite tablet with high hygroscopicity resistance and a preparation method thereof. Background Art

[0002] L-carnitine is a vitamin-like substance with no toxic side effects on the human body. The most prominent physiological function of L-carnitine is to act as a carrier for the transport of fatty acids. It transfers medium-chain fatty acids from the outside of the cell mitochondrial membrane to the inside of the membrane in the form of acetyl-L-carnitine, oxidizes in the mitochondrial matrix, and generates energy. It can be figuratively compared to a forklift that can scoop up fat and burn it in a fuel furnace to provide energy. It acts as a "porter" for fat to mitochondria. It is an internationally recognized safe and non-toxic fat-reducing nutritional enhancer, especially suitable for people who do aerobic exercise to reduce fat, and the effect is obvious. However, L-carnitine has extremely strong hygroscopicity and is not suitable for direct production of solid preparations. Not only is the production process difficult, but the product quality stability cannot be guaranteed. The L-carnitine products currently on sale are mainly its hydrochloride, tartrate and magnesium citrate. Although the hygroscopicity of these L-carnitine salt products has been reduced, the content is not high and the cost is high, which restricts its development.

[0003] Apple fiber is the remaining pomace after apple juice is squeezed. Different from artificially extracted natural dietary fiber or synthetic dietary fiber, apple fiber is a natural mixed dietary fiber rich in dietary fiber, soluble sugars, organic acids, minerals, vitamins and other ingredients. Dietary fiber is called the "seventh nutrient" for humans and has one or more physiological functions such as moisturizing the intestines, regulating and controlling blood sugar concentration, and lowering blood lipids. However, as a natural mixed dietary fiber, apple fiber has poor plasticity and is not suitable for making solid preparations and tablets, especially large and heavy special-shaped tablets. Not only is the production process difficult, the product quality is difficult to guarantee, and the preparation yield is low.

[0004] In previous research, the applicant publicly published an invention patent application with application number CN 106072673 A, entitled "A composition that can effectively reduce body fat ratio", which disclosed a composition that can effectively reduce body fat ratio. The composition includes the following components by weight: 20-70 parts of dietary fiber, 5-15 parts of L-carnitine, 5-15 parts of chitosan and 1-5 parts of tea polyphenols. This invention focuses on the compatibility of raw materials, and the formulated composition can effectively reduce body fat ratio, but it does not solve the technical problem of the difficulty in processing solid preparations of L-carnitine and high-proportion dietary fiber, and the hygroscopicity of L-carnitine cannot guarantee the quality of the product, which ultimately leads to the product being unable to be put into actual production. CN 1520810A discloses a drug for treating fatty liver, which is a western medicine preparation with L-carnitine as the main effective ingredient. The main technical problems to be solved are the portability of the drug, the convenience of use, and the lack of obvious effect. The formula uses a high content of L-carnitine and a sugar alcohol composition, but the patent does not clearly give the relevant parameters for granulation, and therefore the problems of high hygroscopicity, difficulty in tablet forming, low yield, and unqualified product stability cannot be solved.

[0005] Therefore, it is urgent to provide a solid preparation method with high addition ratio of L-carnitine and apple fiber as main raw materials and with high product stability, so that high addition ratio of L-carnitine and dietary fiber can be smoothly put into large-scale production in the field of solid tablets of food and health food. Summary of the invention

[0006] One object of the present invention is to provide a method for preparing L-carnitine composite tablets with high hygroscopic resistance. The preparation method provided by the present invention can effectively solve the problems of strong hygroscopicity, difficulty in processing and forming, poor stability, low yield, etc. in the preparation process of large-scale heavy and irregular tablets with high content of L-carnitine and apple fiber as main raw materials, which is conducive to the smooth implementation of large-scale production.

[0007] Another object of the present invention is to provide a L-carnitine composite tablet prepared by the preparation method as described above.

[0008] In order to achieve the above first object, the present invention adopts the following technical scheme:

[0009] The present invention discloses a method for preparing a L-carnitine composite tablet with high hygroscopicity resistance, comprising the following steps:

[0010] S1, adding 65-80 parts by weight of dietary fiber, 1-3 parts by weight of tea polyphenols, 5-10 parts by weight of isomalt, 1-3 parts by weight of calcium carbonate and 0.75-1.5 parts by weight of hypromellose into a boiling drying granulator for mixing to obtain a mixed powder;

[0011] S2, spraying the citric acid solution evenly on the surface of the mixed powder by spraying, and drying at 50-60° C. until the moisture content of the material particles is 5-7%, to obtain the first spraying material;

[0012] S3, spraying the L-carnitine solution uniformly on the surface of the first spraying material in a spraying manner, so that the L-carnitine is uniformly absorbed in the pores of the dietary fiber and the honeycomb pores generated by the citric acid and calcium carbonate, to obtain a second spraying material;

[0013] S4, using 0.25-0.5 parts of hydroxypropyl methylcellulose solution for spray granulation, so that the hydroxypropyl methylcellulose forms a film and evenly wraps the particles, after the granulation is completed, add 2-3 parts of lubricant and anti-caking agent in total weight, mix evenly, obtain the total mixed material, and obtain L-carnitine composite tablets after tableting and coating.

[0014] Taking into account the typical problems of strong hygroscopicity of L-carnitine and difficulty in forming L-carnitine and dietary fiber, the applicant has made process improvements from the following aspects through a large number of experimental attempts: first, the honeycomb pores generated by the reaction of citric acid and calcium carbonate in step S4 provide a transferable space for the water absorbed by L-carnitine; second, the special structure (long chain structure and fiber pore structure) in each dietary fiber is used to provide sufficient transferable space for the water absorbed by L-carnitine; the third and most important link is to refer to the process of spray granulation, and evenly spray the L-carnitine solution on the surface rich in honeycomb pores and fibers by spraying. The surface of the first spraying material with pores can make L-carnitine smoothly and evenly enter the honeycomb pores produced by the reaction and the pores and long-chain structure of the dietary fiber, so that it can play a role in absorbing water. If there is no spraying process, L-carnitine cannot be evenly absorbed by the fluffy pores, even if dietary fiber, citric acid and calcium carbonate are added to the formula, it cannot play a role in absorbing water; Fourth, in step S4, with the help of the spraying granulation process of hydroxypropyl methylcellulose, the L-carnitine is wrapped up so that it does not directly contact the air to absorb moisture, and the coating treatment is carried out at the same time to achieve the effects of isolating moisture, shading and isolating air.

[0015] Furthermore, in terms of weight, the dietary fiber includes 50-60 parts of apple fiber, 8-10 parts of chitosan and 7-10 parts of resistant dextrin.

[0016] Furthermore, the mass ratio of dietary fiber to L-carnitine is 5-7:1, and the mass ratio of apple fiber to L-carnitine is 4-5:1; the concentration of the L-carnitine solution is 30%-50%, and the solvent is purified water.

[0017] Furthermore, the mass ratio of citric acid to calcium carbonate is 1-2:3; the concentration of the citric acid solution is 10%-25%, and the solvent is purified water.

[0018] Furthermore, during the spraying process of step S2, the temperature is 20-30°C, the spraying speed is 60-90 rpm, the flow rate is 0.6-0.9 L / min, and the atomization pressure is 0.2-0.4 MPa. Under this condition, citric acid molecules and calcium carbonate molecules can slowly react to produce carbon dioxide, so that the material particles produce honeycomb pores. Hydroxypropyl methylcellulose is added to the mixed powder, which can be used as a binder to increase the bridging effect of the material particles, increase the particle friction of calcium citrate, the reaction product of citric acid and calcium carbonate, absorb excess fatty acids, and make the particle tablets easy to form.

[0019] Furthermore, in the spraying process of step S3, the temperature is 50-60°C, the spraying speed is 60-90 rpm, the flow rate is 0.6-0.9 L / min, and the atomization pressure is 0.2-0.4 MPa. The addition method of L-carnitine is crucial. There are few attempts to add L-carnitine in the form of a solution, especially the heating control, spraying speed control, and pressure control during the spraying process, which avoids excessive particle growth, uneven accumulation of L-carnitine, and the appearance of black spots, and avoids uneven mixing and moisture absorption and discoloration.

[0020] Furthermore, in the spray granulation process of step S4, spray granulation is performed using a 3-5% hydroxypropyl methylcellulose solution at a temperature of 20-30° C., a spraying speed of 40-60 rpm, a flow rate of 0.4-0.6 L / min, and an atomization pressure of 0.2-0.4 MPa.

[0021] The concentration of the hydroxypropyl methylcellulose solution used in step S4 is 3-5%. During the spray granulation, the hydroxypropyl methylcellulose can slowly form a film to wrap the fiber mixture that has absorbed L-carnitine. Some commonly used formulation ingredients for preparations, such as sweeteners (such as aspartame), can also be added to the hydroxypropyl methylcellulose solution. With the help of the spraying method, these ingredients can also be sprayed more evenly onto the surface of the material.

[0022] Furthermore, the particle size D90 μm of the granulated product is controlled at 250-350 μm (i.e. 60 mesh), and the moisture content is controlled at 5-7%.

[0023] Furthermore, the lubricant and anti-caking agent are selected from one or more of magnesium stearate, calcium stearate, silicon dioxide and talc.

[0024] Furthermore, the hypromellose used in the present invention is hypromellose E50, and the viscosity of hypromellose E50 is more suitable for the formulation system of the present invention.

[0025] In order to achieve the above second purpose, the present invention adopts the following technical solutions:

[0026] The invention discloses a L-carnitine composite tablet prepared according to the preparation method as described above. The L-carnitine composite tablet is an olive-shaped special-shaped tablet with a tablet weight of 1.0 g / tablet±5%. The pressed tablet has a smooth and beautiful surface, a qualified friability, and a qualified hardness of more than 80N.

[0027] The tablets prepared above are packaged in aluminum-plastic blisters, and the aluminum-plastic blister plates can be further sealed and packaged in polyethylene aluminum film bags. The product quality is qualified in the inspection, the accelerated test stability inspection, and the long-term stability inspection product quality is qualified, and the L-carnitine content is high and stable.

[0028] The beneficial effects of the present invention are as follows:

[0029] The invention provides a tablet preparation method with L-carnitine and apple fiber as main raw materials. The method specifically solves the problems of strong hygroscopicity, difficulty in processing and forming, poor stability, low yield, etc. in the prior art tablets with high content and high addition amount of L-carnitine and dietary fiber as main raw materials. By optimizing the parameters such as the ratio of dietary fiber to L-carnitine, the ratio of citric acid to calcium carbonate, the L-carnitine adding method, the citric acid adding method, etc., the method overcomes the shortcomings of strong hygroscopicity, difficulty in forming, poor stability, etc., which exist in large-sized heavy and special-shaped tablets of solid preparations with high content and high addition amount of L-carnitine directly. At the same time, the method overcomes the shortcomings of difficulty in forming and low yield, etc., which are beneficial to the promotion and application of L-carnitine and natural dietary fiber in tablets in the fields of food and health food. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The specific implementation modes of the present invention will be further described in detail below in conjunction with the accompanying drawings.

[0031] Figure 1 A photograph at 400 times magnification of the granulated particles of Example 1 after the addition of L-carnitine is shown.

[0032] Figure 2 A photograph at 400 times magnification of the granulated particles of Example 4 after the addition of L-carnitine is shown.

[0033] Figure 3 A plain photograph of Example 3 is shown.

[0034] Figure 4 A plain photograph of Example 4 is shown.

[0035] Figure 5 The sample picture of Example 3 after coating is shown.

[0036] Figure 6 The sample picture of Example 4 after coating is shown.

[0037] Figure 7 A picture showing the aluminum-plastic packaging of the coated tablets of Example 2.

[0038] Figure 8 The sample picture of Example 2 after acceleration for 3 months is shown. DETAILED DESCRIPTION

[0039] In order to more clearly illustrate the present invention, the present invention is further described below in conjunction with preferred embodiments and accompanying drawings. Similar components in the accompanying drawings are represented by the same reference numerals. It should be understood by those skilled in the art that the content specifically described below is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0040] Examples 1-4 are the adjustment process of the formula and preparation process of L-carnitine apple fiber tablets in the experimental stage. The specific formula and preparation process are as follows:

[0041] Example 1

[0042] By weight, L-carnitine compound tablets include the following raw materials:

[0043] 9.35 parts of chitosan, 15.52 parts of resistant dextrin, 51.7 parts of apple fiber, 11.83 parts of L-carnitine, 2.8 parts of tea polyphenols, 0.26 parts of aspartame, 1.0 part of hypromellose (E50), 1.0 part of magnesium stearate, and 6.54 parts of sucrose powder.

[0044] The preparation method is as follows:

[0045] 9.35 parts of chitosan, 15.52 parts of resistant dextrin, 51.7 parts of apple fiber and 2.8 parts of tea polyphenols were added into a boiling drying granulator and premixed for 10 minutes; 6.54 parts of sucrose powder were prepared into slurry I with a concentration of 40%; 0.26 parts of aspartame and 0.3 parts of hydroxypropyl methylcellulose were prepared into slurry II with a concentration of 2%; spray granulation was carried out in the order of adding slurry I first and then slurry II; the temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the speed of the peristaltic pump was 80-90 rpm, and the flow rate was 0.8-0.9L / min; after spraying, the granulated particles were dried at 50-60°C to obtain granulated particles with a particle size of 30 mesh.

[0046] 11.83 parts of L-carnitine (crushed through a 80-mesh sieve), 1.0 part of magnesium stearate, 0.7 part of hypromellose and granulated particles were added to a mixer and mixed for 30 minutes. The corresponding parameters of the tablet press were adjusted to obtain tablets with a tablet weight of 1.0 g / tablet ±5%.

[0047] Example 2

[0048] By weight, L-carnitine compound tablets include the following raw materials:

[0049] 9.35 parts of chitosan, 15.52 parts of resistant dextrin, 51.7 parts of apple fiber, 11.83 parts of L-carnitine, 2.8 parts of tea polyphenols, 0.26 parts of aspartame, 1.0 part of hypromellose (E50), 1.0 part of magnesium stearate, and 6.54 parts of sucrose powder.

[0050] The preparation method is as follows:

[0051] 9.35 parts of chitosan, 15.52 parts of resistant dextrin, 51.7 parts of apple fiber, and 2.8 parts of tea polyphenols were added to a boiling drying granulator for premixing for 10 minutes, 6.54 parts of sucrose powder were prepared into slurry I with a concentration of 40%, 0.26 parts of aspartame and 0.3 parts of hydroxypropyl methylcellulose were prepared into slurry II with a concentration of 2%, and spray granulation was performed in the order of adding slurry I first and then slurry II. The temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 80-90 rpm, and the flow rate was 0.8-0.9L / min. After spraying, it was dried at 50-60°C to obtain granulated particles with a particle size of 40 meshes.

[0052] The formulated amount of L-carnitine was mixed with an equal amount of granulated particles, crushed and passed through a 40-mesh sieve, added into a mixer together with 0.7 parts of hydroxypropyl methylcellulose and 1.0 parts of magnesium stearate, and mixed for 30 minutes. The corresponding parameters of the tablet press were adjusted to obtain tablets with a tablet weight of 1.0 g / tablet ±5%.

[0053] Example 3

[0054] By weight, L-carnitine compound tablets include the following raw materials:

[0055] 8.42 parts of chitosan, 2.8 parts of tea polyphenols, 15.57 parts of resistant dextrin, 52.64 parts of apple fiber, 11.27 parts of L-carnitine, 0.26 parts of aspartame, 1.0 parts of hypromellose (E50), 6.54 parts of sucrose powder, 1.0 parts of magnesium stearate, 2.0-3.0 parts of coating powder (out of specification, including 1-1.5 parts of first coating powder for the first layer of coating, and 1-1.5 parts of second coating powder for the second layer of coating, the amount can be fine-tuned within the range).

[0056] The preparation method is as follows:

[0057] Chitosan, resistant dextrin, part of apple fiber (48.89 parts), tea polyphenols, and sucrose powder were added to a granulation pot according to the formula amount and premixed for 10 minutes. 0.26 parts of aspartame and 1.0 parts of hydroxypropyl methylcellulose were prepared into a slurry with a concentration of 2% for spray granulation. The temperature during spray granulation was 30° C., the atomization pressure was 0.2-0.4 MPa, the peristaltic pump speed was 80-90 rpm, and the flow rate was 0.8-0.9 L / min. After spraying, it was dried at 50-60° C. to obtain granulated particles with a particle size of 40 meshes.

[0058] The formulated amount of L-carnitine and part of apple fiber (3.75 parts) were mixed in a ratio of 3:1 and crushed through a 40-mesh sieve, and added into a mixer together with magnesium stearate and granulated particles and mixed for 30 minutes. The corresponding parameters of the tablet press were adjusted to obtain tablets with a tablet weight of 1.0 g / tablet ±5%.

[0059] The coating is divided into two layers. The coating liquid of the first layer is 47.5% ethanol mixed with 1-1.5 parts of coating powder, with a solid content of 8-12%. The main components of the coating powder are hydroxypropyl methylcellulose and polyethylene glycol. The coating conditions are: coating weight gain 0.8-1.5%, coating machine preheated to 40°C, tablet bed not preheated, spray coating with a small flow rate, tablet bed temperature rising synchronously, air inlet temperature 40-60°C, tablet bed temperature maintained at 38-42°C; exhaust 2000-2900 rpm, air inlet 1000-1200 rpm; negative pressure in the pot -50±5Mpa; spray gun 30cm away from tablet bed, coating pot speed 2-6 rpm, atomization / spray gun / flattening pressure set to 0.2Mpa-0.4Mpa, peristaltic pump 20-60 rpm, 33-100ml / minute.

[0060] The second layer of coating liquid is 19% ethanol mixed with 1-1.5 parts of coating powder, with a solid content of 8-14%. The main components of the coating powder are hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide, and red iron oxide. The coating conditions are: coating weight gain 1%-1.5%, inlet air temperature 40-60℃, tablet bed temperature maintained at 38-42℃; exhaust 2000-2900 rpm, inlet 1000-1200 rpm; negative pressure in the pot -50±5Mpa; spray gun 30cm away from the tablet bed, coating pot speed 2-6 rpm, set atomization / spray gun / flattening pressure 0.2Mpa-0.4Mpa, peristaltic pump 20-60 rpm, 33-100ml / minute.

[0061] Example 4

[0062] By weight, L-carnitine compound tablets include the following raw materials:

[0063] 9.0 parts of chitosan, 3.0 parts of tea polyphenols, 7.8 parts of resistant dextrin, 51.0 parts of apple fiber, 13.0 parts of L-carnitine, 0.2 parts of aspartame, 2.0 parts of hypromellose (E50), 1.0 parts of citric acid, 7.0 parts of isomalt, 2.0 parts of calcium carbonate, 3.0 parts of silicon dioxide, 1.0 parts of magnesium stearate, 2.0-3.0 parts of coating powder (out of specification, including 1-1.5 parts of first coating powder for the first layer of coating, and 1-1.5 parts of second coating powder for the second layer of coating, the amount can be fine-tuned within the range).

[0064] Chitosan, resistant dextrin, apple fiber, tea polyphenols, isomalt (crushed), calcium carbonate, and part of hydroxypropyl methylcellulose (1.5 parts) were added to a granulation pot according to the formula amount and premixed for 10 minutes. First, 1.0 part of citric acid was prepared into a slurry I with a concentration of 25% with purified water for spray granulation. The temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 60-90 rpm, and the flow rate was 0.6-0.9L / min. The formula amount of L-carnitine was dissolved in purified water to prepare a slurry II with a concentration of 50% for spray granulation. The temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 60-90 rpm, and the flow rate was 0.6-0.9L / min. Finally, 0.2 parts of aspartame and 0.5 parts of hydroxypropyl methylcellulose were prepared into slurry III with a concentration of 3% for spray granulation. The temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 40-60 rpm, and the flow rate was 0.4-0.6L / min. After spraying, the granulated particles were dried at 50-60°C to obtain granules with a particle size of 40 mesh.

[0065] The magnesium stearate and silicon dioxide in the formula amount were added to the mixer together with the granulated particles and mixed for 30 minutes. The tablet press parameters were adjusted to obtain tablets with a tablet weight of 1.0 g / tablet ± 5%.

[0066] The coating is divided into two layers. The coating liquid of the first layer is 47.5% ethanol mixed with 1-1.5 parts of coating powder, with a solid content of 8-12%. The main components of the coating powder are hydroxypropyl methylcellulose and polyethylene glycol. The coating conditions are: coating weight gain 0.8-1.5%, coating machine preheated to 40°C, tablet bed not preheated, spray coating with a small flow rate, tablet bed temperature rising synchronously, air inlet temperature 40-60°C, tablet bed temperature maintained at 38-42°C; exhaust 2000-2900 rpm, air inlet 1000-1200 rpm; negative pressure in the pot -50±5Mpa; spray gun 30cm away from tablet bed, coating pot speed 2-6 rpm, atomization / spray gun / flattening pressure set to 0.2Mpa-0.4Mpa, peristaltic pump 20-60 rpm, 33-100ml / minute.

[0067] The second layer of coating liquid is 19% ethanol mixed with 1-1.5 parts of coating powder, with a solid content of 8-14%. The main components of the coating powder are hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide, and red iron oxide. The coating conditions are: coating weight gain 1%-1.5%, inlet air temperature 40-60℃, tablet bed temperature maintained at 38-42℃; exhaust 2000-2900 rpm, inlet 1000-1200 rpm; negative pressure in the pot -50±5Mpa; spray gun 30cm away from the tablet bed, coating pot speed 2-6 rpm, set atomization / spray gun / flattening pressure 0.2Mpa-0.4Mpa, peristaltic pump 20-60 rpm, 33-100ml / minute.

[0068] Figure 1 This is a 400-fold magnified photograph of the granulated particles in Example 1 after L-carnitine was added. The granulated particles contain L-carnitine microcrystalline structures, proving that after L-carnitine is added by crushing and sieving, microscopic fine crystals appear unevenly, which can easily cause the local moisture absorption of the tablet to increase. Figure 2 This is a 400-fold magnified photo of the granulated particles in this example after adding L-carnitine. Figure 1 In contrast, there is no L-carnitine microcrystalline structure in the granulated particles in the picture, which proves that the addition of L-carnitine in the form of spraying can make the pores in each dietary fiber absorb evenly, which is beneficial to reduce local moisture absorption of tablets.

[0069] Figure 3 The photograph of the plain tablet after tableting of Example 3 is shown. The plain tablet has many black spots on the surface due to the uneven distribution of L-carnitine and the black spots on the surface caused by moisture absorption. Figure 4 The photo of the plain tablet of Example 4 shows that the black spots on the surface of the plain tablet are significantly reduced. The reason is that the L-carnitine solution is evenly absorbed by the pores of the dietary fiber, and the hygroscopic black spots on the surface of the plain tablet are significantly reduced.

[0070] Figure 5 The sample picture of Example 3 after coating is shown. Since the L-carnitine hygroscopic points on the plain tablets dissolve after encountering the coating liquid, it will cause the sensory "rough surface" on one side to be unqualified. The sample obtained in Example 4 has a smooth surface without the "rough surface" phenomenon (see Figure 6 ).

[0071] Example 1

[0072] By weight, L-carnitine compound tablets include the following raw materials:

[0073] 10.0 parts of chitosan, 3.0 parts of tea polyphenols, 8.8 parts of resistant dextrin, 50.0 parts of apple fiber, 13.0 parts of L-carnitine, 0.2 parts of aspartame, 2.0 parts of hypromellose (E50), 0.5 parts of citric acid, 7.0 parts of isomalt, 1.5 parts of calcium carbonate, 3.0 parts of silicon dioxide, 1.0 part of magnesium stearate, 2.0-3.0 parts of coating powder (out of specification, including 1-1.5 parts of first coating powder for the first layer of coating, and 1-1.5 parts of second coating powder for the second layer of coating, the amount can be fine-tuned within the range).

[0074] Chitosan, resistant dextrin, apple fiber, tea polyphenols, isomalt (crushed), calcium carbonate, and part of hydroxypropyl methylcellulose (1.5 parts) were added to a granulation pot according to the formula amount and premixed for 10 minutes. First, 0.5 parts of citric acid were prepared into a slurry I with a concentration of 25% with purified water for spray granulation. The temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 60-90 rpm, and the flow rate was 0.6-0.9L / min. The formula amount of L-carnitine was dissolved in purified water to prepare a slurry II with a concentration of 50% for spray granulation. The temperature during spray granulation was 50°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 60-90 rpm, and the flow rate was 0.6-0.9L / min. Finally, aspartame and 0.5 parts of hydroxypropyl methylcellulose were prepared into a slurry III with a concentration of 3% for spray granulation. The temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 40-60 rpm, and the flow rate was 0.4-0.6L / min. After spraying, the granulated particles were dried at 50-60°C to obtain granulated particles with a particle size of 60 mesh.

[0075] The magnesium stearate and silicon dioxide in the formula amount were added to the mixer together with the granulated particles and mixed for 30 minutes. The tablet press parameters were adjusted to obtain tablets with a tablet weight of 1.0 g / tablet ± 5%.

[0076] The coating is divided into two layers. The coating liquid of the first layer is 47.5% ethanol mixed with 1-1.5 parts of coating powder, with a solid content of 8-12%. The main components of the coating powder are hydroxypropyl methylcellulose and polyethylene glycol. The coating conditions are: coating weight gain 0.8-1.5%, coating machine preheated to 40°C, tablet bed not preheated, spray coating with a small flow rate, tablet bed temperature rising synchronously, air inlet temperature 40-60°C, tablet bed temperature maintained at 38-42°C; exhaust 2000-2900 rpm, air inlet 1000-1200 rpm; negative pressure in the pot -50±5Mpa; spray gun 30cm away from tablet bed, coating pot speed 2-6 rpm, atomization / spray gun / flattening pressure set to 0.2Mpa-0.4Mpa, peristaltic pump 20-60 rpm, 33-100ml / minute.

[0077] The second layer of coating liquid is 19% ethanol mixed with 1-1.5 parts of coating powder, with a solid content of 8-14%. The main components of the coating powder are hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide, and red iron oxide. The coating conditions are: coating weight gain 1%-1.5%, inlet air temperature 40-60℃, tablet bed temperature maintained at 38-42℃; exhaust 2000-2900 rpm, inlet 1000-1200 rpm; negative pressure in the pot -50±5Mpa; spray gun 30cm away from the tablet bed, coating pot speed 2-6 rpm, set atomization / spray gun / flattening pressure 0.2Mpa-0.4Mpa, peristaltic pump 20-60 rpm, 33-100ml / minute.

[0078] The coated tablets are packaged in aluminum plastic.

[0079] Example 2

[0080] By weight, L-carnitine compound tablets include the following raw materials:

[0081] 8.0 parts of chitosan, 3.0 parts of tea polyphenols, 8.5 parts of resistant dextrin, 50.8 parts of apple fiber, 12.5 parts of L-carnitine, 0.2 parts of aspartame, 2.0 parts of hypromellose (E50), 2.0 parts of citric acid, 7.0 parts of isomalt, 3.0 parts of calcium carbonate, 2.0 parts of silicon dioxide, 1.0 part of magnesium stearate, 2.0-3.0 parts of coating powder (out of specification, including 1-1.5 parts of first coating powder for the first layer of coating, and 1-1.5 parts of second coating powder for the second layer of coating, the amount can be fine-tuned within the range).

[0082] Chitosan, resistant dextrin, apple fiber, tea polyphenols, isomalt (crushed), calcium carbonate, and part of hydroxypropyl methylcellulose (1.5 parts) were added to the granulation pot according to the formula amount and premixed for 10 minutes. First, 2 parts of citric acid were prepared into a slurry I with a concentration of 25% with purified water for spray granulation. The temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 60-90 rpm, and the flow rate was 0.6-0.9L / min. L-carnitine was dissolved in purified water again to prepare a slurry II with a concentration of 50% for spray granulation. The temperature during spray granulation was 50°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 60-90 rpm, and the flow rate was 0.6-0.9L / min. Finally, aspartame and 0.5 parts of hydroxypropyl methylcellulose were prepared into 3% concentration slurry III for spray granulation. The temperature during spray granulation was 30°C, the atomization pressure was 0.2-0.4MPa, the peristaltic pump speed was 40-60 rpm, and the flow rate was 0.4-0.6L / min. After spraying, it was dried at 50-60°C to obtain granulated particles with a particle size of 60 mesh.

[0083] The magnesium stearate and silicon dioxide in the formula amount were added to the mixer together with the granulated particles and mixed for 30 minutes. The tablet press parameters were adjusted to obtain tablets with a tablet weight of 1.0 g / tablet ± 5%.

[0084] The coating is divided into two layers. The coating liquid of the first layer is 47.5% ethanol mixed with 1-1.5 parts of coating powder, with a solid content of 8-12%. The main components of the coating powder are hydroxypropyl methylcellulose and polyethylene glycol. The coating conditions are: coating weight gain 0.8-1.5%, coating machine preheated to 40°C, tablet bed not preheated, spray coating with a small flow rate, tablet bed temperature rising synchronously, air inlet temperature 40-60°C, tablet bed temperature maintained at 38-42°C; exhaust 2000-2900 rpm, air inlet 1000-1200 rpm; negative pressure in the pot -50±5Mpa; spray gun 30cm away from tablet bed, coating pot speed 2-6 rpm, atomization / spray gun / flattening pressure set to 0.2Mpa-0.4Mpa, peristaltic pump 20-60 rpm, 33-100ml / minute.

[0085] The second layer of coating liquid is 19% ethanol mixed with 1-1.5 parts of coating powder, with a solid content of 8-14%. The main components of the coating powder are hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide, and red iron oxide. The coating conditions are: coating weight gain 1%-1.5%, inlet air temperature 40-60℃, tablet bed temperature maintained at 38-42℃; exhaust 2000-2900 rpm, inlet 1000-1200 rpm; negative pressure in the pot -50±5Mpa; spray gun 30cm away from the tablet bed, coating pot speed 2-6 rpm, set atomization / spray gun / flattening pressure 0.2Mpa-0.4Mpa, peristaltic pump 20-60 rpm, 33-100ml / minute.

[0086] The coated tablets are packaged in aluminum plastic and aluminum film.

[0087] Figure 7 The picture of the aluminum-plastic packaging of the coated tablets in this example is shown, and it can be seen that the surface of the coated tablets is intact without any "rough surface".

[0088] Figure 8 The picture of the sample after 3 months of acceleration is shown, which proves that the sample has good stability and the moisture absorption is controllable within the validity period.

[0089] The L-carnitine composite tablets prepared in each example and Examples 1-2 are compared and summarized in Table 1.

[0090] Table 1

[0091]

[0092]

[0093] Table 2 provides detailed stability test data of Example 2. From the results, it can be seen that the L-carnitine composite tablets provided by the present invention have good stability. After 0-3 months of stability testing, there is no significant change in the appearance, total colony count, tablet weight, moisture, ash content, or L-carnitine content of the L-carnitine composite tablets, and the sensory organs are acceptable. The other data meet the requirements, and the overall stability data meets the requirements.

[0094] Table 2

[0095]

[0096]

[0097] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made on the basis of the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A method for preparing a L-carnitine composite tablet having high hygroscopicity resistance, characterized in that: The steps include: S1, adding 65-80 parts by weight of dietary fiber, 1-3 parts by weight of tea polyphenols, 5-10 parts by weight of isomalt, 1-3 parts by weight of calcium carbonate and 0.75-1.5 parts by weight of hypromellose into a boiling drying granulator for mixing to obtain a mixed powder; S2, spraying the citric acid solution evenly on the surface of the mixed powder by spraying to obtain a first spraying material; S3, spraying the L-carnitine solution uniformly on the surface of the first spraying material in a spraying manner, so that the L-carnitine is uniformly absorbed in the pores of the dietary fiber and the honeycomb pores generated by the citric acid and calcium carbonate, to obtain a second spraying material; S4, using 0.25-0.5 parts of hydroxypropyl methylcellulose solution for spray granulation, adding 2-3 parts of lubricant and anti-caking agent by total weight after granulation, mixing evenly to obtain a total mixed material, and obtaining L-carnitine composite tablets after tableting and coating.

2. The preparation method according to claim 1, characterized in that: In terms of weight, the dietary fiber includes 50-60 parts of apple fiber, 8-10 parts of chitosan and 7-10 parts of resistant dextrin.

3. The preparation method according to claim 1, characterized in that: The mass ratio of dietary fiber to L-carnitine is 5-7:1; and the concentration of the L-carnitine solution is 30%-50%.

4. The preparation method according to claim 1, characterized in that: The mass ratio of citric acid to calcium carbonate is 1-2:3; the concentration of the citric acid solution is 10%-25%.

5. The preparation method according to claim 1, characterized in that: During the spraying process in step S2, the temperature is 20-30°C, the spraying speed is 60-90 rpm, the flow rate is 0.6-0.9 L / min, and the atomization pressure is 0.2-0.4 MPa.

6. The preparation method according to claim 1, characterized in that: During the spraying process in step S3, the temperature is 50-60°C, the spraying speed is 60-90 rpm, the flow rate is 0.6-0.9 L / min, and the atomization pressure is 0.2-0.4 MPa.

7. The preparation method according to claim 1, characterized in that: In the spray granulation process of step S4, a 3-5% concentration of hydroxypropyl methylcellulose solution is used for spray granulation at a temperature of 20-30° C., a spray speed of 40-60 rpm, a flow rate of 0.4-0.6 L / min, and an atomization pressure of 0.2-0.4 MPa.

8. The preparation method according to claim 1, characterized in that: After the spray granulation in step S4 is completed, the particle size D90μm of the obtained particles is 250-350μm and the water content is 5-7%.

9. The preparation method according to claim 1, characterized in that: The lubricant is selected from one or more of magnesium stearate, calcium stearate, silicon dioxide and talc.

10. The L-carnitine composite tablet prepared according to the preparation method according to any one of claims 1 to 9.

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