WO2023070985A1

WO2023070985A1 - Abidor hydrochloride tablet and preparation method therefor

Info

Publication number: WO2023070985A1
Application number: PCT/CN2022/075623
Authority: WO
Inventors: 孙立杰; 李磊; 程彦超; 董伟昌; 丁立秀; 左悦; 赵文鹤
Original assignee: 石家庄四药有限公司
Priority date: 2021-11-01
Filing date: 2022-02-09
Publication date: 2023-05-04
Also published as: CN113842370A; CN113842370B

Abstract

Disclosed are an abidor hydrochloride tablet and a preparation method therefor. The abidor hydrochloride tablet comprises the following components in parts by mass: 40-60 parts of abidor hydrochloride, 60-90 parts of a soybean phospholipid, 45-75 parts of a tea polyphenol, 86-120 parts of a filler, 4-15 parts of a disintegrant and 3-9 parts of a lubricant. By compounding the soybean phospholipid with the tea polyphenol, the solubility of abidor hydrochloride is improved, and by adding the disintegrant, the filler and the lubricant and preparing the abidor hydrochloride into tablets, the disintegration effect of the tablets is improved and the dissolution of abidor hydrochloride is significantly promoted, thereby helping to improve the efficacy of abidor hydrochloride tablets.

Description

A kind of Arbidol hydrochloride tablet and preparation method thereof

This patent application claims priority to Chinese Patent Application No. CN202111285132.X filed on November 1, 2021. The disclosure of the prior application is incorporated by reference in its entirety into this application.

technical field

The application relates to the technical field of pharmaceutical preparations, in particular to an arbidol hydrochloride tablet and a preparation method thereof.

Background technique

Arbidol hydrochloride is an off-white crystalline powder, easily soluble in methanol, slightly soluble in ethanol and glacial acetic acid, almost insoluble in water, dilute hydrochloric acid and sodium hydroxide test solution. Arbidol hydrochloride was first listed in Russia in 1993. It induces interferon and enhances immune function to fight against influenza virus. It can effectively treat influenza and other acute respiratory virus infections. Its broad-spectrum antiviral effect is better than that of amantadines. Drugs that have inhibitory effects on influenza A, B and C viruses. Arbidol hydrochloride also has the function of activating macrophages, which can improve the body's resistance to viral infection, and its antiviral market potential is huge. At present, Chinese enterprises mainly develop and produce tablets, capsules, dry suspensions, etc.

Arbidol hydrochloride is rapidly absorbed after oral administration, has a short half-life and poor oral effect. Due to the poor solubility of Arbidol hydrochloride in the gastrointestinal body fluid environment, the results of animal experiments show that its bioavailability in vivo is only about 30%, which leads to its clinical application of 200mg 3~4 times/day, which needs to be taken continuously 5 days. Therefore how to improve the absorption of Arbidol hydrochloride in vivo and improve the bioavailability have become the main direction of product improvement. At present, most of the research is focused on: changing the raw material ligands to improve the solubility of raw materials, such as preparing injections in the form of sulfate or oral liquids with methanesulfonic acid groups; using emulsification or micellar solubilization technology to improve drug solubility, such as preparing into injection etc. Compared with the above studies, oral administration of pharmaceutical tablets has more advantages in terms of safety and compliance, and the preparation process of arbidol hydrochloride tablets is simple and the cost is low. However, the tablet has low solubility, poor disintegration effect, and unsatisfactory in vitro dissolution effect. Therefore, it is urgent to find a method to improve the solubility of Arbidol hydrochloride tablets, and then improve the efficacy of Arbidol hydrochloride tablets. It has become a research hotspot. one.

technical problem

This application provides a kind of arbidol hydrochloride tablet and its preparation method, uses soybean lecithin and tea polyphenol compound to improve the solubility of arbidol hydrochloride, improves the disintegration effect of its tablet, and obviously promotes arbidol hydrochloride The dissolution effect of Al, thereby significantly improving the efficacy of Arbidol hydrochloride.

technical solution

In order to achieve the purpose of the above application, the embodiment of the present application adopts the following technical solutions:

The first aspect of the present application provides an Arbidol hydrochloride tablet, including the following components in parts by mass: Arbidol hydrochloride: 40-60 parts, soybean lecithin: 60-90 parts, tea polyphenols: 45~75 parts, filler: 86~120 parts, disintegrant: 4~15 parts and lubricant: 3~9 parts.

In one of the embodiments, the Arbidol hydrochloride tablet includes the following components in parts by mass: Arbidol hydrochloride: 45-55 parts, soybean lecithin: 70-80 parts, tea polyphenol : 55~65 parts, filler: 100~120 parts, disintegrant: 10~15 parts and lubricant: 7~9 parts.

Further optionally, the Arbidol hydrochloride tablet includes the following components in parts by mass: Arbidol hydrochloride: 50 parts, soybean lecithin: 75 parts, tea polyphenols: 60 parts, filler: 108 parts, disintegrant: 15 parts and lubricant: 9 parts.

The prescription amount of the Arbidol hydrochloride tablet significantly improves the solubility and bioavailability of the Arbidol hydrochloride, improves the disintegration effect of the tablet, and obviously promotes the dissolution of the preparation, thereby significantly improving the solubility of the Arbidol hydrochloride. efficacy.

In one embodiment, the disintegrant is croscarmellose sodium, crospovidone or sodium carboxymethyl starch.

The above-mentioned disintegrant can make the tablet disintegrate rapidly in the body, increase the solubility and bioavailability of insoluble drugs, thereby significantly improving the drug effect of arbidol hydrochloride.

In one of the embodiments, the filler is microcrystalline cellulose, corn starch, calcium hydrogen phosphate or lactose.

In one of the embodiments, the lubricant is calcium stearate, sodium stearyl fumarate or stearic acid.

The second aspect of the present application provides a kind of preparation method of Arbidol hydrochloride tablet, at least comprises the following steps:

Step 1, sieving the arbidol hydrochloride and tea polyphenols respectively;

Step 2. Weigh each component according to the mass fraction of each component in the above-mentioned Arbidol hydrochloride tablet, and dissolve the Arbidol hydrochloride, tea polyphenols and soybean lecithin with dehydrated alcohol to obtain a phospholipid complex substance solution;

Step 3, mixing the filler, disintegrant and the phospholipid complex solution, granulating, drying, and sizing to obtain phospholipid complex granules;

Step 4, mixing the lubricant with the phospholipid complex particles, compressing into tablets, and coating to obtain the arbidol hydrochloride tablets.

In one embodiment, in step 1, the fineness of the sieved screen is 50 mesh.

In one of the embodiments, in step 2, the quality of the absolute ethanol is 1.5 to 2.5 times the total mass of the arbidol hydrochloride, tea polyphenols and soybean lecithin, and the dissolution temperature is 45° C. 55°C.

The preferred heating method for dissolution is heating in a water bath.

The optimal process parameters can uniformly disperse arbidol hydrochloride in the inactive tea polyphenols and soybean lecithin adjuvant carrier in a highly dispersed state such as molecular, amorphous or microcrystalline state, effectively improving the solubility of insoluble drugs.

In one of the embodiments, the specific process of step three is: placing the filler and disintegrating agent in a fluidized bed granulation pot, and spraying the phospholipid complex solution into the In a granulation pot, granulate, dry, and granulate to obtain phospholipid complex particles; wherein, the process parameters of the granulation are: the air intake volume is 500m ³ /h ~ 1200m ³ /h, and the air intake temperature is 40°C ~ 60°C, the atomization pressure is 0.1MPa~0.2MPa, the liquid feeding speed of the phospholipid complex solution is 3rpm~10rpm; the air inlet temperature of the drying is 50°C~70°C; the sieve aperture of the granulation is 1.2 mm~2.0mm.

In one of the embodiments, the phospholipid complex solution is added with a peristaltic pump.

In this application, the phospholipid complex solution is volatilized and dried instantly by means of fluidized bed top-spray granulation, thereby promoting the solidification of the phospholipid complex, and at the same time helping to bind and granulate with fillers, thereby shortening the process flow.

In one embodiment, in step 4, the mixing speed is 10 rpm to 15 rpm, and the mixing time is 5 min to 10 min.

In one embodiment, in step 4, the core hardness of the compressed tablet is 40N-70N.

In one of the embodiments, in step 4, the coating adopts a coating liquid with a concentration of 10wt%~12wt%, and the weight gain of the coating layer is 3%~4%, that is, the weight gain of the coating layer It is 3%~4% of the total weight of the tablet core.

It can be understood that the numerical ranges disclosed in the embodiments of the present application can be any value in the range interval; the disclosed numerical ranges or values are only better choices. Of course, in other embodiments, other numerical ranges or values may also be used, and are not limited thereto.

Beneficial effect

Compared with the prior art, the Arbidol hydrochloride tablet provided by the application has the following advantages:

Arbidol hydrochloride raw material itself has poor water solubility, it is difficult to disintegrate when prepared into tablets, and the dissolution effect in vitro is poor. This application forms a highly dispersed phospholipid carrier system by dissolving soybean lecithin and arbidol hydrochloride, which can dissolve arbidol hydrochloride It is highly dispersed in molecular form in the inactive soybean lecithin carrier. Based on the structure of soybean lecithin containing a nitrogen or phosphorus hydrophilic end and two hydrophobic hydrocarbon chains, it can significantly improve the solubility of Arbidol hydrochloride. And improve the dissolution rate of arbidol hydrochloride, while soybean phospholipids and free phenolic hydroxyl groups in arbidol hydrochloride form intermolecular hydrogen bonds, obviously improve the absorption effect of arbidol hydrochloride through the gastrointestinal tract, and then obtain higher The blood concentration of the drug is high, and the elimination of the drug in the body is slow, and the bioavailability is significantly improved; however, due to the certain viscosity of soybean lecithin, it is difficult to disintegrate the tablet when it is used in the tablet, so it is necessary to supplement it with tea polyphenols. Prepared into a complex highly dispersed phospholipid carrier system, the free phenolic hydroxyl groups in the tea polyphenol structure form intermolecular hydrogen bonds with soybean lecithin, thereby further improving the solubility of Arbidol hydrochloride, and taking advantage of the good water solubility of tea polyphenols and relatively The low viscosity further increases the water-soluble channel of the tablet, thereby improving the disintegration effect of the preparation and promoting the dissolution effect of the preparation.

This application improves the solubility of arbidol hydrochloride by compounding soybean lecithin and tea polyphenols, and prepares tablets by adding disintegrants, fillers and lubricants to improve the disintegration effect of the tablets and significantly accelerate the preparation process. The dissolution effect, thereby significantly improving the efficacy of Arbidol hydrochloride.

Compared with the prior art, the preparation method of the Arbidol hydrochloride tablet provided by the application has the following advantages:

In this application, Arbidol hydrochloride is prepared into tablets by preparing a complex highly dispersed phospholipid complex solution, granulating, tableting and other processes, which improves the solubility and disintegration effect of Arbidol hydrochloride, and then improves its biological properties. Utilization reduces the number of administrations and solves the problem of low dissolution of tablets in vitro.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the accompanying drawings that need to be used in the embodiments. Obviously, the accompanying drawings in the following description are only some embodiments of the present application. For Those of ordinary skill in the art can also obtain other drawings based on these drawings without making creative efforts.

Fig. 1 is the XRD figure one that the application test example 4 provides;

Fig. 2 is the XRD pattern 2 provided by Test Example 4 of the present application.

Embodiment of this application

In order to make the purpose, technical solution and advantages of the present application clearer, the present application will be further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described here are only used to explain the present application, and are not intended to limit the present application.

Example 1

The embodiment of the present application provides an arbidol hydrochloride tablet, including the following components in parts by mass: arbidol hydrochloride: 50 g, soybean lecithin: 75 g, tea polyphenols: 60 g, microcrystalline cellulose : 108 g, sodium carboxymethyl starch: 15 g and calcium stearate: 9 g.

The preparation method of above-mentioned Arbidol hydrochloride sheet, comprises the following steps:

Step 1, passing the arbidol hydrochloride and tea polyphenols through a 50 mesh sieve respectively;

Step 2, each component is weighed according to the above-mentioned proportioning, and described arbidol hydrochloride, tea polyphenol and soybean lecithin are dissolved with dehydrated alcohol, obtain phospholipid complex solution; The quality of described dehydrated alcohol is 2 times the total mass of Arbidol hydrochloride, tea polyphenols and soybean lecithin, and the dissolution condition is 50°C heated in a water bath;

Step 3, placing the microcrystalline cellulose and sodium carboxymethyl starch in a fluidized bed granulation pot, spraying the phospholipid complex solution into the granulation pot by top spray granulation, and granulating , dried, and granulated to obtain phospholipid complex granules, wherein the process parameters for granulation are: air intake volume is 500m ³ /h, air intake temperature is 40°C, atomization pressure is 0.15MPa, and liquid addition speed of phospholipid complex solution It is 8rpm; the air inlet temperature of the drying is 60°C; the sieve aperture of the granulation is 1.5mm;

Step 4, putting the calcium stearate and the phospholipid complex granules into a three-dimensional mixer for mixing, tableting and coating to obtain 1000 tablets of Arbidol hydrochloride, wherein the mixing speed is 10rpm, The time is 5 minutes, the hardness of the tablet core is controlled at 50N, the coating is coated with a coating solution with a concentration of 12wt%, and the weight gain of the coating layer is 3%.

Example 2

The embodiment of the present application provides an arbidol hydrochloride tablet, including the following components in parts by mass: arbidol hydrochloride: 45 g, soybean lecithin: 80 g, tea polyphenols: 75 g, corn starch: 100 g g, croscarmellose sodium: 8 g and calcium stearate: 6 g.

Step 2, taking each component according to the above-mentioned proportioning; and dissolving the arbidol hydrochloride, tea polyphenols and soybean lecithin in absolute ethanol to obtain a phospholipid complex solution; the quality of the absolute ethanol is 2.5 times the total mass of Arbidol hydrochloride, tea polyphenols and soybean lecithin, and the dissolution condition is 55°C heated in a water bath;

Step 3, placing the cornstarch and croscarmellose sodium in a fluidized bed granulation pot, spraying the phospholipid complex solution into the granulation pot by means of top spray granulation, and preparing granulation, drying, and granulation to obtain phospholipid complex granules, wherein the process parameters for granulation are: air intake volume is 800m ³ /h, air intake temperature is 55°C, atomization pressure is 0.18MPa, liquid addition of phospholipid complex solution The rotating speed is 9rpm; the air inlet temperature of the drying is 50°C; the sieve aperture of the granulation is 1.8mm;

Step 4, putting the calcium stearate and the phospholipid complex granules into a three-dimensional mixer for mixing, tableting and coating to obtain 1000 tablets of Arbidol hydrochloride, wherein the mixing speed is 10rpm, The time is 8 minutes, the hardness of the tablet core is controlled at 70N, the coating is coated with a coating solution with a concentration of 12wt%, and the weight gain of the coating layer is 3.5%.

Example 3

The embodiment of the present application provides an arbidol hydrochloride tablet, which includes the following components in parts by mass: arbidol hydrochloride: 55 g, soybean lecithin: 70 g, tea polyphenols: 45 g, lactose: 120 g, Crospovidone: 4 g and stearic acid: 9 g.

Step 2, each component is weighed according to the above-mentioned proportioning, and described arbidol hydrochloride, tea polyphenols and soybean lecithin are dissolved in absolute ethanol to obtain a phospholipid complex solution; the quality of the absolute ethanol is 1.5 times the total mass of Arbidol hydrochloride, tea polyphenols and soybean lecithin, and the dissolution condition is 45°C heated in a water bath;

Step 3, placing the lactose and crospovidone in a fluidized bed granulation pot, spraying the phospholipid complex solution into the granulation pot by top spray granulation, granulating, drying, Graining to obtain phospholipid complex granules, wherein the process parameters for granulation are: air intake volume is 1200m ³ /h, air intake temperature is 50°C, atomization pressure is 0.2MPa, and liquid feeding speed of phospholipid complex solution is 5rpm; The air inlet temperature of the drying is 60°C; the sieve aperture of the granulation is 1.2mm;

Step 4, put the stearic acid and the phospholipid complex granules into a three-dimensional mixer for mixing, tableting and coating to obtain 1000 pieces of the Arbidol hydrochloride tablets, wherein the mixing speed is 10rpm, time The hardness of the compressed tablet core was controlled at 40N, the coating was coated with a coating solution with a concentration of 12wt%, and the weight gain of the coating layer was 3.5%.

Example 4

The embodiment of the present application provides an Arbidol hydrochloride tablet, including the following components in parts by mass: Arbidol hydrochloride: 40 g, soybean lecithin: 60 g, tea polyphenols: 65 g, calcium hydrogen phosphate: 120 g, sodium starch glycolate: 14 g and sodium stearyl fumarate: 3 g.

Step 2, each component is weighed according to the above-mentioned proportioning, and described arbidol hydrochloride, tea polyphenols and soybean lecithin are dissolved in absolute ethanol to obtain a phospholipid complex solution; the quality of the absolute ethanol is 2 times the total mass of Arbidol hydrochloride, tea polyphenols and soybean lecithin, and the dissolution condition is 50°C heated in a water bath;

Step 3, placing the calcium hydrogen phosphate and sodium carboxymethyl starch in a fluidized bed granulation pot, spraying the phospholipid complex solution into the granulation pot by means of top spray granulation, and granulating, Dry and granulate to obtain phospholipid complex granules, wherein the process parameters for granulation are: the air intake volume is 900m ³ /h, the air intake temperature is 45°C, the atomization pressure is 0.1MPa, and the liquid addition speed of the phospholipid complex solution is 6rpm; the air inlet temperature of the drying is 60°C; the sieve aperture of the granulation is 1.5mm;

Step 4, putting the sodium stearyl fumarate and the phospholipid complex particles into a three-dimensional mixer for mixing, tableting and coating to obtain 1000 tablets of the Arbidol hydrochloride tablet, wherein the mixing speed is 15rpm, time 5min, tablet core hardness controlled at 40N, coating with a coating solution with a concentration of 12wt%, and the weight gain of the coating layer was 3%.

Example 5

The embodiment of the present application provides an Arbidol hydrochloride tablet, including the following components in parts by mass: Arbidol hydrochloride: 60 g, soybean lecithin: 90 g, tea polyphenols: 55 g, microcrystalline cellulose : 86g, sodium carboxymethyl starch: 10 g and calcium stearate: 7 g.

Step 2, each component is weighed according to the above-mentioned proportioning, and described arbidol hydrochloride, tea polyphenols and soybean lecithin are dissolved in absolute ethanol to obtain a phospholipid complex solution; the quality of the absolute ethanol is 2.5 times the total mass of Arbidol hydrochloride, tea polyphenols and soybean lecithin, and the dissolution condition is 45°C heated in a water bath;

Step 3, placing the microcrystalline cellulose and sodium carboxymethyl starch in a fluidized bed granulation pot, spraying the phospholipid complex solution into the granulation pot by top spray granulation, and granulating , dried, and granulated to obtain phospholipid complex granules, wherein the process parameters for granulation are: air intake volume is 800m ³ /h, air intake temperature is 60°C, atomization pressure is 0.15MPa, and the liquid feeding speed of phospholipid complex solution is It is 5rpm; the air inlet temperature of the drying is 60°C; the sieve aperture of the granulation is 1.8mm;

Step 4, putting the calcium stearate and the phospholipid complex granules into a three-dimensional mixer for mixing, tableting and coating to obtain 1000 pieces of the Arbidol hydrochloride tablets, wherein the mixing speed is 15rpm, The time is 10 minutes, the hardness of the tablet core is controlled at 70N, the coating is coated with a coating solution with a concentration of 10wt%, and the weight gain of the coating layer is 4%.

In order to better illustrate the technical solution of the present application, a further comparison is made below through comparative examples and examples of the present application.

Comparative example 1

This comparative example provides a kind of Arbidol hydrochloride injection emulsion, is made up of following components: Arbidol hydrochloride 4.8g, soybean lecithin 15g, Tween 80 15g, gum arabic 15g, n-propanol 15g, soybean oil 300g , 45g of glycerin, 5g of vitamin C, an appropriate amount of acetic acid-sodium acetate buffer solution, and water for injection to 1000mL;

The above-mentioned Arbidol hydrochloride injection emulsion preparation method is as follows:

Weigh each component according to the above ratio, add arbidol hydrochloride, soybean lecithin, Tween 80, gum arabic, and n-propanol into soybean oil, heat and stir the dissolved first solution as the oil phase; Add glycerin and vitamin C to 500mL water for injection, heat and stir to dissolve the second solution as the water phase; add the oil phase to the water phase under shear and mix to make colostrum. The shear speed is 10000r/min. Time 20min; add water for injection to 1000ml in colostrum, and adjust pH to 2.5 with acetic acid-sodium acetate buffer solution, and make milk particles through high-pressure homogenization, homogenization pressure 600bar, homogenization times 6 times; Granular filtration, filling, and sterilization to obtain arbidol hydrochloride injection emulsion.

Comparative example 2

This comparative example provides a kind of Arbidol hydrochloride capsule, and the dosage of each prescription is as follows:

The preparation method of the above-mentioned Arbidol hydrochloride capsules is as follows:

Weigh each component according to the above ratio, mix Arbidol hydrochloride with microcrystalline cellulose MCC-CG and pregelatinized starch evenly, pulverize, pass through 80 sieves, and obtain the primary mixture; Add ketone K-30 and sodium lauryl sulfate into water, mix well to get a mixed solution; mix the primary mixture and 70wt% disintegrant (low-substituted hydroxypropyl cellulose LH-22 and crospovidone XL) Mix evenly, add to the fluidized bed, spray the mixed solution into the fluidized bed, granulate, dry at 55°C, sieve through a 40-mesh sieve to obtain granules; mix the granules with the remaining disintegrant and gas-phase micro-powdered silica gel evenly, Filling to obtain Arbidol hydrochloride capsules.

Comparative example 3

Original drug: Arbidol hydrochloride tablets (Арбидол) produced by Фармстандарт-Лексредства, product batch number: 40220.

Comparative example 4

This comparative example provides an Arbidol hydrochloride tablet, including the following components in parts by mass: Arbidol hydrochloride: 50 g, soybean lecithin: 75 g, lactose: 60 g, microcrystalline cellulose: 108 g , sodium carboxymethyl starch: 15 g and calcium stearate: 9 g.

The preparation method of the above-mentioned Arbidol hydrochloride tablet is consistent with that of Example 1, only the tea polyphenol in Example 1 is replaced with the lactose in Comparative Example 4, and the rest are the same, and will not be repeated here.

In order to better illustrate the characteristics of the Arbidol hydrochloride tablets provided by the embodiments of the application, the Arbidol hydrochloride tablets prepared in Examples 1~3 and the Arbidol hydrochloride preparations prepared in Comparative Examples 1~4 are carried out below. Performance testing.

Test Example 1 Solubility

Grinding the preparations of Arbidol hydrochloride raw materials, Examples 1~3 and Comparative Examples 2~4 respectively; For ~4 and raw material samples, use a constant temperature oscillator to measure the equilibrium solubility in purified water and pH 6.8 phosphate buffer solution. At 37 ° C, three parallel experiments are performed. After oscillating with a constant temperature oscillator for 24 hours, pass through a 0.45-micron filter membrane, dilute the sample, take the test solution and the reference solution, according to the ultraviolet-visible spectrophotometry ("Chinese Pharmacopoeia" 2020 Edition Four General Rules 0401), at a wavelength of 315nm The absorbance was measured respectively, and the solubility was converted according to the dilution factor. Comparative Example 1 was tested for solubility according to the above detection method, and the results are shown in Table 1.

As can be seen from Table 1, the solubility of arbidol hydrochloride raw material in water and pH6.8 phosphate buffer solution is all poor, wherein it is almost insoluble in pH6.8 solution; comparative examples 2～3 all adopt raw material and auxiliary material The preparation method of grinding and pulverizing has no significant change in drug solubility, which is consistent with the drug solubility of the original preparation; the solubility of the arbidol hydrochloride tablets prepared in comparative example 4 in water and in pH6.8 solution all has certain improvement, and in water The solubility of the drug has been improved by about 2.5 times; in the Arbidol hydrochloride tablets prepared in Examples 1 to 3, tea polyphenols have been added, and the solubility has been significantly improved, which has been increased by about 4 times in water, and the solubility in pH6.8 solution has reached It is about 0.25mg/mL, which shows that the equilibrium solubility of the drug can be effectively improved by compounding soybean lecithin and tea polyphenols.

The Arbidol hydrochloride injection emulsion prepared in Comparative Example 1 has the highest solubility in water, and the solubility of the Arbidol hydrochloride tablets prepared in Examples 1 to 3 of the present application is basically equivalent to that of the Comparative Example 1 emulsion, thus indicating , Through the compounding of soybean lecithin and tea polyphenols, the solubility of Arbidol hydrochloride tablets is significantly improved.

Table 1 Solubility test results

Test example 2

The disintegration time of the Arbidol hydrochloride tablets prepared in Examples 1-3 and Comparative Examples 3-4 was measured according to the disintegration time limit detection method of the 2020 edition of the Four General Rules 0902 of the "Chinese Pharmacopoeia", and the results are shown in Table 2 below. It can be seen from Table 2 that the disintegration time of the arbidol hydrochloride tablet is significantly shortened and the disintegration performance is significantly improved by compounding soybean lecithin and tea polyphenols.

Table 2 Disintegration time

Test example 3

According to the second method of the four general rules of the "Chinese Pharmacopoeia" 2020 edition, use pH6.8 phosphate buffer solution plus 0.05% Tween 900ml as the dissolution medium, and the rotation speed is 75 rpm, according to the second method of the four general rules of the "Chinese Pharmacopoeia" 2020 edition operate. After 5min, 10min, 15min, 30min, 60min, 90min, and 120min, take 10mL of the dissolution solution, and immediately replenish the dissolution medium at the same temperature and volume. Take the test solution and the reference solution, and measure the absorbance at a wavelength of 315nm according to the ultraviolet-visible spectrophotometry ("Chinese Pharmacopoeia" 2020 Edition Four General Rules 0401), respectively, and calculate each tablet of Arbidol hydrochloride at different times. of dissolution.

The arbidol hydrochloride preparations prepared in Examples 1-3 and Comparative Examples 2-4 were subjected to in vitro dissolution testing, and the testing results are shown in Table 3 below. As can be seen from Table 3, the dissolution curve of the Arbidol hydrochloride preparation prepared by comparative examples 2 to 3 can only dissolve about 18% when it reaches 120min, and the dissolution curve of the Arbidol hydrochloride sheet prepared by comparative example 4 reaches 120min Only 59.5% can be dissolved at the same time, and the dissolution curve of the Arbidol hydrochloride sheet prepared in Examples 1 ~ 3 reaches about 95% when the dissolution curve reaches 120min. This shows that the combination of soybean lecithin and Arbidol hydrochloride can improve its biological However, the combination of tea polyphenols and soybean lecithin can significantly improve the disintegration effect of the preparation and accelerate the dissolution of the preparation.

Table 3 In vitro dissolution curve test results

Test example 4

The raw materials of Arbidol hydrochloride, the preparations prepared in Example 1 and Comparative Examples 2-3 were characterized by X-ray diffraction (XRD), and the results are shown in Figure 1 and Figure 2. As can be seen from Figure 1, in the raw material of Arbidol hydrochloride, the comparative example 2 prepared by the grinding technology of the drug and the auxiliary material, and the comparative example 3 of the original preparation, the drug all exists in the form of crystals, and the diffraction angle of the drug is basically the same; from the figure 2, it can be seen that the characteristic crystal diffraction peak of Arbidol hydrochloride in Example 1 disappears and presents an amorphous state, which shows that a highly dispersed state is formed between Arbidol hydrochloride, tea polyphenols and soybean lecithin Solid dispersion, improves drug solubility.

The solubility, disintegration time, in vitro dissolution and X-ray diffraction detection results of the Arbidol hydrochloride tablets prepared in Examples 4-5 are all equivalent to the results of Examples 1-3.

The above description is only a preferred embodiment of the application, and is not intended to limit the application. Any modification, equivalent replacement or improvement made within the spirit and principles of the application shall be included in the protection of the application. within range.

Claims

An Arbidol hydrochloride tablet, characterized in that: it comprises the following components in parts by mass: Arbidol hydrochloride: 40-60 parts, soybean lecithin: 60-90 parts, tea polyphenols: 45 parts ~75 parts, filler: 86 parts~120 parts, disintegrant: 4 parts~15 parts and lubricant: 3 parts~9 parts.
Arbidol hydrochloride tablet as claimed in claim 1, is characterized in that: comprise each component of following mass fraction: Arbidol hydrochloride: 45 ~ 55 parts, soybean lecithin: 70 ~ 80 parts, tea Polyphenol: 55~65 parts, filler: 100~120 parts, disintegrant: 10~15 parts and lubricant: 7~9 parts.
Arbidol hydrochloride tablet as claimed in claim 2, is characterized in that: comprise each component of following mass fraction: Arbidol hydrochloride: 50 parts, soybean lecithin: 75 parts, tea polyphenol: 60 parts, Filling agent: 108 parts, disintegrant: 15 parts and lubricant: 9 parts.
The Arbidol hydrochloride tablet according to any one of claims 1 to 3, wherein the disintegrant is croscarmellose sodium, crospovidone or sodium carboxymethyl starch.
The Arbidol hydrochloride tablet according to any one of claims 1 to 3, wherein the filler is microcrystalline cellulose, corn starch, calcium hydrogen phosphate or lactose.
The Arbidol hydrochloride tablet according to any one of claims 1 to 3, wherein the lubricant is calcium stearate, sodium stearyl fumarate or stearic acid.
A kind of preparation method of Arbidol hydrochloride sheet, it is characterized in that: comprise the following steps at least:

Step 1, sieving Arbidol hydrochloride and tea polyphenols respectively;

Step 2, weigh each component according to the mass parts of each component in the Arbidol hydrochloride tablet described in any one of claims 1 to 6, and combine the Arbidol hydrochloride, the tea polyphenol Dissolving the soybean lecithin with absolute ethanol to obtain a phospholipid complex solution;

Step 3, mixing the filler, the disintegrant and the phospholipid complex solution, granulating, drying, and sizing to obtain phospholipid complex granules;

Step 4, mixing the lubricant with the phospholipid complex particles, compressing into tablets, and coating to obtain the arbidol hydrochloride tablets.
The preparation method of Arbidol hydrochloride tablet as claimed in claim 7, is characterized in that: in step 1, the sieve mesh fineness of described sieving is 50 orders; And/or

In step 2, the mass of the absolute ethanol is 1.5-2.5 times the total mass of the arbidol hydrochloride, the tea polyphenols and the soybean lecithin, and the dissolution temperature is 45°C-55°C.
The preparation method of Arbidol hydrochloride tablet as claimed in claim 7, is characterized in that: the concrete process of step 3 is: described filler and described disintegrant are placed in fluidized bed granulation pot, adopt Top-spray granulation method sprays the phospholipid complex solution into the granulation pot, granulates, dries, and granulates to obtain phospholipid complex granules; wherein, the process parameters of the granulation are: the air intake volume is 500m 3 /h ~ 1200m 3 /h, the air inlet temperature is 40°C ~ 60°C, the atomization pressure is 0.1MPa ~ 0.2MPa, the liquid feeding speed of the phospholipid complex solution is 3rpm ~ 10rpm; the dry air inlet The temperature is 50° C. to 70° C.; the aperture of the sieve for the granulation is 1.2 mm to 2.0 mm.
The preparation method of Arbidol hydrochloride tablet as claimed in claim 7, is characterized in that: in step 4, the rotating speed of described mixing is 10rpm～15rpm, and the time of mixing is 5min～10min; And/or

In step 4, the tablet core hardness of the compressed tablet is 40N~70N; and/or

In step 4, a coating solution with a concentration of 10wt%-12wt% is used for the coating, and the weight gain of the coating layer of the coating is 3%-4%.