Method for preparing microcrystalline cellulose from cotton linters and its applications

Abstract

The present application belongs to the field of microcrystalline cellulose preparation, and provides a method for preparing microcrystalline cellulose from linter fibers. The method comprises the following steps: (1) dispersing and defibrating high-purity cellulose of linter to screen out linter fibers of 50-100 mesh; (2) drying the linter fibers obtained in step (1) and balancing the moisture; (3) acidolysis of the linter fibers obtained in step (2); (4) filtering the reaction product with a sand core funnel, washing clean. Collecting the solid, and freeze-drying for 48 h, then obtaining the microcrystalline cellulose. The raw material is screened, and the linter fibers are subjected to acid hydrolysis, which improves the selectivity of acid hydrolysis, and directionally prepares the microcrystalline cellulose with a particle size distribution range of 80-120 um and 120-180 um, which provides a theoretical basis for the directional preparation and control of microcrystalline cellulose, and has important guiding significance for the actual production of microcrystalline cellulose.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of microcrystalline cellulose preparation, and particularly relates to a method for preparing microcrystalline cellulose from cotton linter fibers and application thereof. BACKGROUND

[0002] The information disclosed in this Background section is only for the purpose of increasing the understanding of the general background of the application and does not necessarily constitute an admission or a recognition that the information forms part of the prior art that is already known in any country in the world.

[0003] Microcrystalline cellulose is a white, odorless, water-insoluble fine powder or particle, which is a cellulose derivative obtained by treating natural cellulose. In the pharmaceutical industry, microcrystalline cellulose has become a new type of pharmaceutical excipient widely used in solid drug preparations. As a biomass product, the raw material sources of microcrystalline cellulose are wide, such as cotton fabric, wood, bagasse, bean hulls, tea dregs, oil palm fibers, algae, reed, corn cobs and Jerusalem artichoke stems, etc. Acid hydrolysis of cellulose is the most commonly used method for preparing microcrystalline cellulose, which has the advantages of low cost, short time consumption, high yield, mature preparation method and industrial production, etc., but still has the problems of large particle size fluctuation and inability to directionally prepare microcrystalline cellulose with a specific particle size distribution interval. SUMMARY

[0004] In order to solve the above problems, the present application provides a method for preparing microcrystalline cellulose from cotton linter fibers and application thereof. The selectivity of hydrochloric acid hydrolysis is improved by starting from raw materials, taking high-purity cotton linter cellulose as raw material, screening out cotton linter fibers with 50-120 mesh and high alpha-cellulose content (more than 95%), and through hydrochloric acid hydrolysis, microcrystalline cellulose with a particle size distribution interval of 80-120 μm and 120-180 μm can be directionally prepared. At the same time, the prepared microcrystalline cellulose has better sustained-release effect for western medicine tablets.

[0005] In order to achieve the above purpose, the present application adopts the following technical solutions:

[0006] In a first aspect, the present application provides a method for preparing microcrystalline cellulose from cotton linter fibers, comprising:

[0007] The cotton linter fibers are dispersed and defibered, and then cotton linter fibers with 50-100 mesh are screened out;

[0008] The cotton linter fibers are subjected to acid hydrolysis by using an acid to obtain a reaction product;

[0009] The reaction product is washed to neutral and freeze-dried to obtain the microcrystalline cellulose.

[0010] In the cotton linter fibers, the alpha-cellulose content is more than 95%.

[0011] In some embodiments, the average length of the fiber is 0.760 mm, the average width of the fiber is 35.7 μm, the moisture is 74.11%, the crystallinity is 73.82%, and the water retention value is 0.9503 g / g.

[0012] In some embodiments, the acid is hydrochloric acid.

[0013] In some embodiments, the specific conditions of the acid hydrolysis are that the amount of hydrochloric acid is 3% to 7%, the reaction temperature is 75 to 90℃, the reaction time is 30 to 60 min, and the solid-liquid ratio is 1:30 to 40; the reaction time is 30 to 60 min.

[0014] In some embodiments, the acid hydrolysis is carried out under mechanical stirring.

[0015] In some embodiments, the washing uses hot water, the temperature of the hot water is 90 to 100℃, and the amount of the hot water used for washing is 1 to 2 L.

[0016] In some embodiments, the freeze-drying temperature is -30 to -40℃, and the freeze-drying time is 48 to 60 h.

[0017] In some embodiments, the particle size distribution range of the microcrystalline cellulose is 80 to 120 μm, or 120 to 180 μm.

[0018] In a second aspect of the present application, the above-mentioned microcrystalline cellulose is provided for use in pharmacy.

[0019] In a third aspect of the present application, a ibuprofen tablet is provided, which is composed of the following components by weight: the microcrystalline cellulose of claim 7 35 to 40 parts, lactose 35 to 40 parts, ibuprofen 20 to 25 parts, magnesium stearate 2 to 5 parts, talc 3 to 5 parts, stevioside 2 to 5 parts, and corn starch 3 to 5 parts.

[0020] In a fourth aspect of the present application, a preparation method of the above-mentioned ibuprofen tablet is provided, which comprises:

[0021] The components are ground and mixed, and then directly compressed to obtain the tablet.

[0022] Advantages of the present application

[0023] (1) The present application improves the selectivity of acid hydrolysis by starting from raw materials, and analyzes traditional raw materials such as cotton linters with high purity cellulose. It is found that: the cotton linter fibers with high α-cellulose content (more than 95%) and specific particle size range (50 to 120 mesh) can be directly used for the preparation of microcrystalline cellulose, which can improve the selectivity of acid hydrolysis and realize the directional preparation of 80 to 120 μm and 120 to 180 μm interval microcrystalline cellulose.

[0024] (2) The present application selects inorganic acid hydrochloric acid to carry out acid hydrolysis on the fiber, through the screening of raw materials and the adjustment of hydrochloric acid treatment conditions, the prepared microcrystalline cellulose has more uniform particle size distribution, the yield in the interval of 80-120 μm and 120-180 μm is higher, the efficiency of acid hydrolysis is greatly improved, and low acid consumption, low energy consumption and high yield can be realized in actual production.

[0025] (3) The present application uses microcrystalline cellulose in the preparation of ibuprofen tablets, as a filler and a disintegrant, the ibuprofen tablets prepared by the method have better sustained release effect.

[0026] (4) The preparation method is simple, practical and easy to popularize. DETAILED DESCRIPTION

[0027] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used in the present application have the same meaning as generally understood by those skilled in the art to which the present application belongs.

[0028] The present application will be further described in detail below in combination with specific examples, it should be noted that the specific examples are an explanation of the present application rather than a limitation.

[0029] In the following examples, high-purity cotton linter cellulose is taken as an example, the α-cellulose content is 98.67%, the moisture content is 7.75%, and the ash content is 0.05%.

[0030] The test of particle size, disintegration time, dissolution rate and friability all uses the general method in the industry.

[0031] Example 1

[0032] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board was weighed, torn and dispersed in water, soaked for 24 hours, then defibrated, and the fiber was screened by a Bauer screen instrument, and 50-120 mesh cotton linter fiber was screened out.

[0033] (2) The cotton linter fiber obtained in step (1) was dried and transferred to a sealed bag to balance the moisture, and the cotton linter fiber was characterized, the average length of the fiber was 0.760 mm, and the average width of the fiber was 35.7 μm.

[0034] (3) 2.0 g (absolutely dry) of cotton linter fiber obtained in step (2) was weighed and transferred to a reaction container, hydrochloric acid and deionized water were added to the reaction container, the amount of hydrochloric acid was 5%, and the solid-liquid ratio was 1:30. The reaction was carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature was 85℃, and the reaction time was 60 min.

[0035] (4) The reaction product obtained in step (3) is rapidly cooled, filtered with a sand core funnel, and the solid hydrolysis product is washed with 1 L of hot water at 90-100°C until neutral. The solid hydrolysis product is collected, and after freeze-drying for 48 h, a microcrystalline cellulose product is obtained.

[0036] (5) Ibuprofen tablets are prepared, and the specific components and proportions are: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All components are thoroughly ground and mixed, and direct compression is used for tabletting, with the tablet mass controlled at 200 mg.

[0037] Results: The D50 of the cotton linter fiber microcrystalline cellulose obtained is 42.1 μm, and the particle size distribution range of 80-120 μm accounts for 57.32%. The disintegration time of the ibuprofen tablet prepared under this condition is 1321 s, the dissolution rate is 56.18%, and the friability is 0.79%.

[0038] Example 2

[0039] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board is weighed, torn apart, and dispersed in water, soaked for 24 hours, and then defibered. The fibers are screened using a Bauer screen, and cotton linter fibers of 50-120 mesh are screened out.

[0040] (2) The cotton linter fibers obtained in step (1) are spun dry, transferred to a sealed bag, and balanced for moisture. The basic characterization of the cotton linter fibers is performed, with an average fiber length of 0.760 mm and an average fiber width of 35.7 μm.

[0041] (3) 2.0 g (absolutely dry) of the cotton linter fibers obtained in step (2) is weighed and transferred to a reaction container. Hydrochloric acid and deionized water are added to the reaction container, with the amount of hydrochloric acid being 6% and the solid-liquid ratio being 1:30. The reaction is carried out in a heat collecting constant temperature heating magnetic stirrer, with the reaction temperature being 85°C and the reaction time being 60 min.

[0042] (4) The reaction product obtained in step (3) is rapidly cooled, filtered with a sand core funnel, and the solid hydrolysis product is washed with 1 L of hot water at 90-100°C until neutral. The solid hydrolysis product is collected, and after freeze-drying for 48 h, a microcrystalline cellulose product is obtained.

[0043] (5) Ibuprofen tablets are prepared, and the specific components and proportions are: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All components are thoroughly ground and mixed, and direct compression is used for tabletting, with the tablet mass controlled at 200 mg.

[0044] Results: The D50 of the obtained cotton linter fiber microcrystalline cellulose is 32.7 μm, the particle size distribution interval of 80-120 μm accounts for 57.55%, the disintegration time of the ibuprofen tablet prepared under the condition is 1253 s, the dissolution rate is 57.12%, and the friability is 1.01%.

[0045] Example 3

[0046] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board was torn into pieces and dispersed in water, soaked for 24 hours, and then defibered. The fibers were screened by a Bauer screen instrument, and cotton linter fibers of 50-120 meshes were screened out.

[0047] (2) The cotton linter fibers obtained in step (1) were dried and transferred to a sealed bag to balance the moisture. The basic characterization of the cotton linter fibers was performed, and the average length of the fibers was 0.760 mm, and the average width of the fibers was 35.7 μm.

[0048] (3) 2.0 g (absolutely dry) of the cotton linter fibers obtained in step (2) was transferred to a reaction container, and hydrochloric acid and deionized water were added to the reaction container, wherein the amount of hydrochloric acid was 7%, and the solid-liquid ratio was 1:30. The reaction was carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature was 85°C, and the reaction time was 60 min.

[0049] (4) The reaction product obtained in step (3) was quickly cooled, filtered with a sand core funnel, and washed with 1 L of hot water at 90-100°C until the solid hydrolysis product was neutral. The solid hydrolysis product was collected, and after 48 h of freeze-drying, the microcrystalline cellulose product was obtained.

[0050] (5) Ibuprofen tablets were prepared, and the specific components and proportions were as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All the components were thoroughly ground and mixed, and the direct compression method was used for tabletting, and the mass of the tablet was controlled to be 200 mg.

[0051] Results: The D50 of the obtained cotton linter fiber microcrystalline cellulose is 30.1 μm, the particle size distribution interval of 80-120 μm accounts for 53.75%, the disintegration time of the ibuprofen tablet prepared under the condition is 1145 s, the dissolution rate is 62.37%, and the friability is 0.87%.

[0052] Example 4

[0053] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board was torn into pieces and dispersed in water, soaked for 24 hours, and then defibered. The fibers were screened by a Bauer screen instrument, and cotton linter fibers of 50-120 meshes were screened out.

[0054] (2) The cotton linter fibers obtained in step (1) were spun dry, transferred to a sealed bag to balance the moisture, and the cotton linter fibers were characterized. The average fiber length was 0.760 mm, and the average fiber width was 35.7 μm.

[0055] (3) 2.0 g (absolute dry) of the cotton linter fibers obtained in step (2) were weighed and transferred to a reaction vessel. Hydrochloric acid and deionized water were added to the reaction vessel, wherein the amount of hydrochloric acid was 5%, and the solid-liquid ratio was 1:30. The reaction was carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature was 85°C, and the reaction time was 70 min.

[0056] (4) The reaction product obtained in step (3) was rapidly cooled, filtered with a sand core funnel, and washed with 1 L of hot water at 90-100°C until the solid hydrolysis product was neutral. The solid hydrolysis product was collected and freeze-dried for 48 h to obtain a microcrystalline cellulose product.

[0057] (5) Ibuprofen tablets were prepared, and the specific components and proportions were as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All the components were thoroughly ground and mixed, and direct compression was used for tabletting, with the tablet mass controlled at 200 mg.

[0058] Results: The D50 of the cotton linter microcrystalline cellulose obtained was 34.3 μm, the particle size distribution range of 20-80 μm accounted for 55.63%, and the disintegration time of the ibuprofen tablet prepared under the above conditions was 1379 s, the dissolution rate was 52.71%, and the friability was 0.97%.

[0059] Example 5

[0060] (1) 500 g of absolute dry cotton linter high-purity cellulose pulp board was weighed, torn apart and dispersed in water, soaked for 24 hours, and then defibered. The fibers were screened using a Bauer screen separator, and cotton linter fibers of 50-120 mesh were screened out.

[0061] (2) The cotton linter fibers obtained in step (1) were spun dry, transferred to a sealed bag to balance the moisture, and the cotton linter fibers were characterized. The average fiber length was 0.760 mm, and the average fiber width was 35.7 μm.

[0062] (3) 2.0 g (absolute dry) of the cotton linter fibers obtained in step (2) were weighed and transferred to a reaction vessel. Hydrochloric acid and deionized water were added to the reaction vessel, wherein the amount of hydrochloric acid was 5%, and the solid-liquid ratio was 1:30. The reaction was carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature was 90°C, and the reaction time was 50 min.

[0063] (4) The reaction product obtained in step (3) is rapidly cooled, filtered with a sand core funnel, and the solid hydrolysis product is washed with 1 L of hot water at 90-100°C until neutral. The solid hydrolysis product is collected, and after freeze-drying for 48 h, a microcrystalline cellulose product is obtained.

[0064] (5) Ibuprofen tablets are prepared, and the specific components and proportions are as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All components are thoroughly ground and mixed, and direct compression is used for tabletting, with the tablet mass controlled at 200 mg.

[0065] Results: The D50 of the cotton linter fiber microcrystalline cellulose obtained is 29.7 μm, and the particle size distribution range of 80-120 μm accounts for 53.91%. The disintegration time of the ibuprofen tablet prepared under this condition is 1265 s, the dissolution rate is 51.29%, and the friability is 0.87%.

[0066] Example 6

[0067] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board is torn into pieces and dispersed in water, soaked for 24 hours, and then defibered. The fibers are screened using a Bauer screen, and cotton linter fibers of 50-120 mesh are screened out.

[0068] (2) The cotton linter fibers obtained in step (1) are spun dry and transferred to a sealed bag to balance the moisture. The basic characterization of the cotton linter fibers is performed, and the average fiber length is 0.760 mm, and the average fiber width is 35.7 μm.

[0069] (3) 2.0 g (absolutely dry) of the cotton linter fibers obtained in step (2) is transferred to a reaction container, and hydrochloric acid and deionized water are added to the reaction container. The amount of hydrochloric acid is 5%, and the solid-liquid ratio is 1:30. The reaction is carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature is 95°C, and the reaction time is 60 min.

[0070] (4) The reaction product obtained in step (3) is rapidly cooled, filtered with a sand core funnel, and the solid hydrolysis product is washed with 1 L of hot water at 90-100°C until neutral. The solid hydrolysis product is collected, and after freeze-drying for 48 h, a microcrystalline cellulose product is obtained.

[0071] (5) Ibuprofen tablets are prepared, and the specific components and proportions are as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All components are thoroughly ground and mixed, and direct compression is used for tabletting, with the tablet mass controlled at 200 mg.

[0072] Results: The D50 of the obtained microcrystalline cellulose is 27.6 μm, the particle size distribution range of 80-120 μm accounts for 54.79%, the disintegration time of the ibuprofen tablet prepared under the condition is 986 s, the dissolution rate is 57.96%, and the friability is 0.85%.

[0073] Comparative Example 1

[0074] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board was torn into pieces and dispersed in water, soaked for 24 hours, and then defibered. The fibers were screened by a Bauer screen instrument, and 12-18 mesh long fibers were screened out.

[0075] (2) The long fibers obtained in step (1) were dried and transferred to a sealed bag to balance the moisture. The long fibers were characterized, with an average fiber length of 2.562 mm and an average fiber width of 35.5 μm.

[0076] (3) 2.0 g (absolutely dry) of long fibers obtained in step (2) was transferred to a reaction container, and hydrochloric acid and deionized water were added to the reaction container. The amount of hydrochloric acid was 5%, and the solid-liquid ratio was 1:30. The reaction was carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature was 85℃, and the reaction time was 60 min.

[0077] (4) The reaction product obtained in step (3) was quickly cooled, filtered with a sand core funnel, and washed with 1 L of hot water at 90-100℃ until the solid hydrolysis product was neutral. The solid hydrolysis product was collected and freeze-dried for 48 h to obtain the microcrystalline cellulose product.

[0078] (5) Ibuprofen tablets were prepared, and the specific ingredients and proportions were as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All ingredients were thoroughly ground and mixed, and direct compression was used for tabletting, with the tablet mass controlled at 200 mg.

[0079] Results: The D50 of the obtained long fiber microcrystalline cellulose is 35.9 μm, the particle size distribution range of 80-120 μm accounts for 52.21%, the disintegration time of the ibuprofen tablet prepared under the condition is 1089 s, the dissolution rate is 56.53%, and the friability is 0.96%.

[0080] Comparative Example 2

[0081] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board was torn into pieces and dispersed in water, soaked for 24 hours, and then defibered. The fibers were screened by a Bauer screen instrument, and 12-18 mesh long fibers were screened out.

[0082] (2) The long fibers obtained in step (1) were spun dry, transferred to a sealed bag to balance the moisture, and the long fibers were characterized. The average length of the fibers was 2.562 mm, and the average width of the fibers was 35.5 μm.

[0083] (3) 2.0 g (absolute dry) of the long fibers obtained in step (2) were transferred to a reaction vessel, and hydrochloric acid and deionized water were added to the reaction vessel. The amount of hydrochloric acid was 6%, and the solid-liquid ratio was 1:30. The reaction was carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature was 85°C, and the reaction time was 60 min.

[0084] (4) The reaction product obtained in step (3) was quickly cooled, filtered with a sand core funnel, and washed with 1 L of hot water at 90-100°C until the solid hydrolysis product was neutral. The solid hydrolysis product was collected and freeze-dried for 48 h to obtain a microcrystalline cellulose product.

[0085] (5) Ibuprofen tablets were prepared, and the specific components and proportions were as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All the components were thoroughly ground and mixed, and direct compression was used to compress the tablets, with the tablet mass controlled at 200 mg.

[0086] Results: The D50 of the long fiber microcrystalline cellulose obtained was 31.2 μm, the particle size distribution range of 80-120 μm accounted for 53.74%, and the disintegration time of the ibuprofen tablets prepared under this condition was 1105 s, the dissolution rate was 52.53%, and the friability was 1.02%.

[0087] Comparative Example 3

[0088] (1) 500 g of absolute dry cotton linter high purity cellulose pulp board was torn and dispersed in water, soaked for 24 hours, and then defibered. The fibers were screened using a Bauer screen separator, and long fibers of 12-18 mesh were screened out.

[0089] (2) The long fibers obtained in step (1) were spun dry, transferred to a sealed bag to balance the moisture, and the long fibers were characterized. The average length of the fibers was 2.562 mm, and the average width of the fibers was 35.5 μm.

[0090] (3) 2.0 g (absolute dry) of the long fibers obtained in step (2) were transferred to a reaction vessel, and hydrochloric acid and deionized water were added to the reaction vessel. The amount of hydrochloric acid was 7%, and the solid-liquid ratio was 1:30. The reaction was carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature was 85°C, and the reaction time was 60 min.

[0091] (4) The reaction product obtained in step (3) is rapidly cooled, filtered with a sand core funnel, and the solid hydrolysis product is washed with 1 L of hot water at 95-100°C until neutral. The solid hydrolysis product is collected, and after freeze-drying for 48 h, a microcrystalline cellulose product is obtained.

[0092] (5) Ibuprofen tablets are prepared, and the specific components and proportions are as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All components are thoroughly ground and mixed, and direct compression is used for tabletting, with the tablet mass controlled at 200 mg.

[0093] Results: The D50 of the long-fiber microcrystalline cellulose obtained is 26.4 μm, and the particle size distribution range of 20-80 μm accounts for 52.11%. The disintegration time of the ibuprofen tablet prepared under this condition is 1055 s, the dissolution rate is 59.49%, and the friability is 0.92%.

[0094] Comparative Example 4

[0095] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board is torn into pieces and dispersed in water, soaked for 24 hours, and then defibered. The fibers are screened with a Bauer screen instrument, and long fibers of 12-18 mesh are screened out.

[0096] (2) The long fibers obtained in step (1) are spun dry and transferred to a sealed bag to balance the moisture. The long fibers are characterized, and the average length of the fibers is 2.562 mm, and the average width of the fibers is 35.5 μm.

[0097] (3) 2.0 g (absolutely dry) of long fibers obtained in step (2) is transferred to a reaction container, and hydrochloric acid and deionized water are added to the reaction container. The amount of hydrochloric acid is 5%, and the solid-liquid ratio is 1:30. The reaction is carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature is 85°C, and the reaction time is 75 min.

[0098] (4) The reaction product obtained in step (3) is rapidly cooled, filtered with a sand core funnel, and the solid hydrolysis product is washed with 1 L of hot water at 90-100°C until neutral. The solid hydrolysis product is collected, and after freeze-drying for 48 h, a microcrystalline cellulose product is obtained.

[0099] (5) Ibuprofen tablets are prepared, and the specific components and proportions are as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All components are thoroughly ground and mixed, and direct compression is used for tabletting, with the tablet mass controlled at 200 mg.

[0100] Results: The D50 of the long fiber microcrystalline cellulose obtained is 27.3 μm, the particle size distribution interval of 20-80 μm accounts for 52.86%, the disintegration time of the ibuprofen tablet prepared under the condition is 1143 s, the dissolution is 53.66%, and the friability is 1.12%.

[0101] Comparative Example 5

[0102] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board was torn into pieces and dispersed in water, soaked for 24 hours, and then defibered. The fibers were screened by a Bauer screen instrument, and long fibers of 12-18 meshes were screened out.

[0103] (2) The long fibers obtained in step (1) were spun dry and transferred to a sealed bag to balance the moisture. The long fibers were characterized, with an average fiber length of 2.562 mm and an average fiber width of 35.5 μm.

[0104] (3) 2.0 g (absolutely dry) of long fibers obtained in step (2) was transferred to a reaction container, and hydrochloric acid and deionized water were added to the reaction container. The amount of hydrochloric acid was 5%, and the solid-liquid ratio was 1:30. The reaction was carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature was 90℃, and the reaction time was 60 min.

[0105] (4) The reaction product obtained in step (3) was quickly cooled, filtered with a sand core funnel, and washed with 1 L of 90-100℃ hot water to neutralize the solid hydrolysis product. The solid hydrolysis product was collected, and after 48 h of freeze-drying, the microcrystalline cellulose product was obtained.

[0106] (5) Ibuprofen tablets were prepared, and the specific ingredients and proportions were as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All ingredients were thoroughly ground and mixed, and direct compression was used for tabletting, with the tablet mass controlled at 200 mg.

[0107] Results: The D50 of the long fiber microcrystalline cellulose obtained is 27.5 μm, the particle size distribution interval of 80-120 μm accounts for 51.02%, the disintegration time of the ibuprofen tablet prepared under the condition is 1102 s, the dissolution is 53.68%, and the friability is 0.91%.

[0108] Comparative Example 6

[0109] (1) 500 g of absolutely dry cotton linter high-purity cellulose pulp board was torn into pieces and dispersed in water, soaked for 24 hours, and then defibered. The fibers were screened by a Bauer screen instrument, and long fibers of 12-18 meshes were screened out.

[0110] (2) The long fibers obtained in step (1) are spun dry, transferred to a sealed bag to balance the moisture, and the long fibers are characterized. The average length of the fibers is 2.562 mm, and the average width of the fibers is 35.5 μm.

[0111] (3) 2.0 g (dry weight) of the long fibers obtained in step (2) are transferred to a reaction vessel, and hydrochloric acid and deionized water are added to the reaction vessel. The amount of hydrochloric acid is 5%, and the solid-to-liquid ratio is 1:30. The reaction is carried out in a heat collecting constant temperature heating magnetic stirrer, the reaction temperature is 95°C, and the reaction time is 60 min.

[0112] (4) The reaction product obtained in step (3) is rapidly cooled, filtered with a sand core funnel, and washed with 1 L of hot water at 90-100°C until the solid hydrolysis product is neutral. The solid hydrolysis product is collected, and after freeze-drying for 48 h, the microcrystalline cellulose product is obtained.

[0113] (5) Ibuprofen tablets are prepared. The specific components and proportions are as follows: microcrystalline cellulose 35%, lactose 35%, ibuprofen 20%, magnesium stearate 2%, talc 3%, stevioside 2%, and corn starch 3%. All the components are thoroughly ground and mixed, and the direct compression method is used to compress the tablets, with the tablet mass controlled at 200 mg.

[0114] Results: The D50 of the long fiber microcrystalline cellulose obtained is 23.2 μm, the particle size distribution range of 80-120 μm accounts for 50.12%, and the disintegration time of the ibuprofen tablet prepared under this condition is 923 s, the dissolution rate is 68.71%, and the friability is 0.91%.

[0115] From the comparison of Example 1 and Comparative Example 1, it can be seen that the use of cotton linter fibers with high α-cellulose content (more than 95%) and a specific particle size range (50-120 mesh) for the preparation of microcrystalline cellulose can effectively increase the content of microcrystalline cellulose in the 80-120 μm and 120-180 μm ranges, achieving directional preparation. At the same time, the use of this raw material for ibuprofen tablets effectively prolongs the disintegration time.

[0116] The above only describes preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing microcrystalline cellulose from cotton linter fibers, characterized in that, include: (1) Weigh 500g of oven-dried cotton linter high-purity cellulose pulp board, tear it into pieces and disperse it in water. After soaking for 24 hours, it is disintegrated. The fibers are then sieved using a Pall sieve to separate 50-120 mesh cotton linter fibers. The α-cellulose content in the cotton linter high-purity cellulose pulp board is 98.67%. (2) The cotton linters obtained in step (1) were spun dry and transferred to a sealed bag to balance the moisture. The cotton linters were then characterized. The average length of the cotton linters was 0.760 mm and the average width of the cotton linters was 35.7 μm. (3) Weigh 2.0g of the oven-dry cotton lint obtained in step (2), transfer it to the reaction vessel, add hydrochloric acid and deionized water to the reaction vessel, the amount of hydrochloric acid is 5% and the solid-liquid ratio is 1:30; the reaction is carried out in a heat-collecting constant temperature heating magnetic stirrer, the reaction temperature is 85℃ and the reaction time is 70min. (4) Cool the reaction product obtained in step (3) quickly, filter it with a sintered glass funnel, and wash the solid hydrolysis product thoroughly with 1L of hot water at 90~100℃ until it is neutral; The solid hydrolysis products were collected and freeze-dried for 48 hours to obtain microcrystalline cellulose products.

2. The microcrystalline cellulose prepared by the method of claim 1, characterized in that, The microcrystalline cellulose has a D50 of 34.3 μm, and the particle size distribution range of 20~80 μm accounts for 55.63%.

3. The application of the microcrystalline cellulose according to claim 2 in pharmaceutical manufacturing.

4. An ibuprofen tablet, characterized in that, It is composed of the following raw materials in parts by weight: 35 parts of microcrystalline cellulose as described in claim 2, 35 parts of lactose, 20 parts of ibuprofen, 2 parts of magnesium stearate, 3 parts of talc, 2 parts of stevioside, and 3 parts of corn starch.

5. A method for preparing ibuprofen tablets according to claim 4, characterized in that, include: The raw material components are ground and mixed, and then compressed into tablets using the direct compression method to obtain the final product.