KR100801589B1 - Cefuroxime axetil granule and process for the preparation thereof - Google Patents

Abstract

The present invention relates to a high bioavailability and excellent stability, high purity shielded cefuroxime axetyl granules and a method for preparing the same, amorphous cepuroxime acetil solid dispersion or amorphous cepuroxime axetyl, HLB is in the range of 1 to 8 It provides cefuroxime axetyl granules prepared by mixing and melting a nonionic surfactant having a melting point of 35 to 80 ° C., and a disintegrant. The cefuroxime axetyl granules according to the present invention are excellent in the stability of the drug, the bitter taste is effectively shielded to improve the medication compliance, reproducible production, it can be useful for oral administration of cefuroxime axetyl.

Description

Cefuroxime AXETIL GRANULES AND MANUFACTURING METHOD THEREOF {CEFUROXIME AXETIL GRANULE AND PROCESS FOR THE PREPARATION THEREOF}             

1 is a result of comparing the amount of drug released over time during dispersing of the water of cefuroxime axetil (cefuroxime axetil) formulation and the comparative formulation (Ginnet ^R tablet, GSK) according to the present invention,

Figure 2 is a dissolution test results of the cefuroxime axetyl formulation and the comparative formulation (Ginnet ^R tablet) according to the present invention,

Figure 3 is the result of comparing the blood concentration of the drug with time when the administration of the cefuroxime axetyl preparation and the comparative preparation (Gennet ^R tablet) according to the present invention.

The present invention relates to cefuroxime axetyl granules having high bioavailability, excellent stability, and high drug compliance, and a preparation method thereof.

Cefuroxime axetil is a cephalosporin-based oral antibiotic that exhibits high activity against a wide range of Gram-positive and negative microorganisms. Sepuroxime axetyl usually has three types of polymorphisms: crystalline with a melting point of about 180 ° C., high melting point like amorphous with a melting point of about 135 ° C., and low melting point like amorphous with a melting point of about 70 to 95 ° C. There is this. Although cefuroxime axetyl has good antimicrobial activity, there are two considerations in the preparation of dry syrup.

First, due to the crystalline form of the drug substance itself is poorly soluble and due to the nature of the drug itself forms a gel phase by contact with a water-soluble medium there is a problem that the rate of dissolution and absorption in the gastrointestinal tract is inhibited.

In order to improve this problem, the present inventors have already prepared an amorphous cefuroxime axetyl solid dispersion with improved dissolution rate and bioavailability as described in Korean Patent No. 342943, which can be formulated or used as a raw material itself.

Second, despite the excellent antimicrobial activity, due to the very bitter taste of the drug itself, which can not be masked by the sweetening and flavoring agents commonly applied to granules, there is a problem that not only children but also general adult patients are reluctant to take orally.

In Korean Patent Publication No. 1999-0009097 of GlaxoSmithKline (GSK), in order to shield the bitter taste of cefuroxime axetyl, the drug is dispersed in a molten stearic acid and spray-dried, and the product is cooled using a low temperature air stream. By this, a method of producing granules is disclosed. However, the granules prepared by the above method are to be dispersed in water but are suspended in water due to the physical properties of stearic acid itself, so there is a problem that it is difficult to take a certain amount when taking the homogeneity. In addition, the first taste after taking a certain degree of masking the sweet taste by the sweetener and flavor, but has a disadvantage in that the aftertaste is very low, especially in compliance with the medication.

Therefore, the present inventors have studied a new method that can overcome the disadvantages of the existing method, the amorphous cepuroxime axetyl, including a nonionic surfactant and disintegrant having a HLB range of 1 ~ 8 and a melting point of 35 ~ 80 ℃ The present invention was completed by developing a composition for oral administration, and confirming that the composition is easy to take and reproducibly masks bitter taste, and exhibits excellent stability and good release property.

It is an object of the present invention to provide cefuroxime axetyl granules which are excellent in dissolution rate and stability and effectively mask the bitter taste.

Another object of the present invention is to provide a method for producing the granules.

In accordance with the above object, in the present invention, cefu prepared by mixing and melting amorphous cepuroxime axetyl solid dispersion or amorphous cepuroxime axetyl, a nonionic surfactant having a HLB of 1 to 8 and a melting point of 35 to 80 ° C, and a disintegrant Provides Roxim Axetyl Granules.

In addition, in the present invention 1) the HLB is in the range of 1 to 8 and melting by applying heat to a nonionic surfactant having a melting point of 35 to 80 ℃; 2) adding and dispersing an amorphous cefuroxime axetyl solid dispersion or a mixture of amorphous cefuroxime axetyl and a disintegrant to the molten surfactant of step 1); And 3) cooling the molten mixture of step 2) and then pulverizing it to a predetermined size to produce granules.

Hereinafter, the present invention will be described in detail.

The cefuroxime axetyl granules according to the present invention are amorphous cefuroxime axetyl solid dispersion or amorphous cefuroxime axetyl, a nonionic surfactant having a HLB in the range of 1 to 8 and a melting point of 35 to 80 ° C., and a disintegrant. And nonionic surfactants, coatings, and pharmaceutically acceptable additives that are at least HLB 8 to aid in formulation.

Referring to each component of the composition for oral administration is as follows.

(1) Sepuroxime Axetyl

Sepuroxime axetyl is used as an active ingredient of the present invention. Amorphous cefuroxime acetyl solid dispersion prepared by the method described in Patent No. 342943, or amorphous cefuroxime axetyl raw material is preferred. They have the same bitter taste as crystalline cefuroxime axetyl, but are amorphous and have very good solubility and dissolution properties.

(2) nonionic surfactants having an HLB ranging from 1 to 8 and a melting point of from 35 to 80 ° C;

Nonionic surfactants used in the compositions of the present invention are essential ingredients in obtaining a formulation capable of masking the bitter taste of cefuroxime axetyl. If the nonionic surfactant having a low melting point of 35 to 80 ℃ can be melted at a low temperature, the manufacturing process is facilitated and the decomposition of the drug can be suppressed to ensure stability. In particular, nonionic surfactants having a range of 1 to 8 of the HLB (Hydrophilic Lipophilic Balance) are oil-based surfactants that have a very low affinity with water, so when used with a disintegrant, they are stored for several days or more with water. Even if the disintegration is not easy to prevent the dissolution of the drug.

Of the nonionic surfactants having a HLB in the range of 1 to 8 and a melting point of 35 to 80 ° C., all surfactants which can be used in medicine can be used in the present invention. Among them, representative examples suitable for the purpose of the present invention are as follows.

1) Sugars and derivatives thereof having hydrophilic addition to polyols

Representative is Sucrose fatty acid esters (37318-31-3). It is marketed under the trade name (SUCROSE FAESTER (DK ES.F-20W)) (Japanese Dai-ichi Kogyo Seiyaku Co., Ltd.) and has an HLB value of about 2 and a melting point of about 65 to 68 ° C. Carrier.

2) Sorbitan fatty acid esters

Representative examples include sorbitan monopalmitate, sorbitan monostearate and sorbitan tristearate. The product is marketed under the trade names SOLFA-400, SOLFA-600 and SOLFA-650 (Ilshin emulsifier), with HLB values of 6.7, 4.7 and 2.1, respectively. It is an oil-soluble carrier which is 65 degreeC.

3) Propylene glycol fatty acid esters

A typical one is an oil-soluble carrier having a melting point of about 38 to 50 ° C., available under the trade name of Aldo (Sampoong BnF).

In addition, virtually any surfactant capable of masking the bitter taste of cepuroxime axetyl with a nonionic surfactant having a HLB in the range of 1 to 8 and a melting point of 35 to 80 ° C. is applicable.

According to the present invention, nonionic surfactants having a HLB in the range of 1 to 8 and a melting point of 35 to 80 ° C. are 0.5 to 50 parts by weight, preferably 1 to 20, based on 1 part by weight of cefuroxime axetyl as a pharmacologically active ingredient. It can be used in the amount of parts by weight.

(3) nonionic surfactants having at least HLB 8

In the present invention, the nonionic surfactant having an HLB 8 or higher increases hydrophilicity so that the non-ionic surfactant having an HLB exhibiting properties close to oils or waxes in the range of 1 to 8 and having a melting point of 35 to 80 ° C is emulsified and dispersed in water stably. Thereby increasing release properties. As long as the above effects are exhibited, any of the nonionic surfactants having a pharmaceutically acceptable HLB 8 or higher may be used, and for example, the following components may be used.

1) Reaction products of natural or hydrogenated vegetable oils with ethylene glycol:

Polyoxyethylene glycolated natural or hydrogenated vegetable oils, for example polyoxyethylene glycolated natural or hydrogenated castor oils, and the like, cremophores (Cremophor, BASF Corporation) or HCO (Nikkol Corporation).

2) polyoxyethylene-sorbitan-fatty acid esters:

Esters of mono or trilauryl, palmityl, stearyl or oleyl are sold under the trade name Tween, ICI.

3) polyoxyethylene fatty acid esters:

Polyoxyethylene stearic acid ester is commercially available under the trade name MyRZ (Myrj, ICI).

4) Polyoxyethylene-polyoxypropyl-

ene) block copolymers:

It is marketed under the trade names Poloxamer (BASF), Pluronic (BASF) or Lutrol (BASF).

5) sodium dioctylsulfosuccinate or sodium lauryl sulfate

6) Propylene glycol mono- or di-fatty acid esters:

For example, propylene glycol dilaurate, propylene glycol ricinoleate, propylene glycol caprylic-capric acid diester (trade name: Myglyol 840, Huls) Can be used. Among the surfactants listed above, polyoxyethylene products, polyoxyethylene-polyoxypropylene block copolymers and polyoxyethylene sorbitan fatty acid esters of hydrogenated vegetable oils are particularly preferred.

The surfactant of HLB 8 or more of the present invention may be used in an amount of 0.01 to 10 parts by weight, preferably 0.05 to 2 parts by weight, based on 1 part by weight of cefuroxime acetyl.

(4) disintegrant

Disintegrants are used as the components necessary for the rapid disintegration of nonionic surfactants having a HLB in the range of 1 to 8 and a melting point of 35 to 80 ° C. to show the desired elution. Disintegrating agents which can be used for this purpose are as follows.

1) microcrystalline cellulose

2) Crosslinked Sodium Carboxymethyl Cellulose

3) crosslinked polyvinyl pyrrolidone

4) Ion exchange resins, in particular amberlite IRP-88

5) alginic acid

6) sodium starch glycolate

Alginate is used as the most preferable component among these components.

The disintegrant of the present invention may be used in an amount of 0.1 to 40 parts by weight, preferably 0.2 to 20 parts by weight, based on 1 part by weight of cefuroxime axetyl.

(5) coating material

Granules containing a nonionic surfactant having a HLB of the present invention in the range of 1 to 8 and having a melting point of 35 to 80 ° C. may be coated in a conventional manner using a suitable coating material as necessary. As a coating material which can be used for this purpose, an enteric material for protecting cefuroxime axetyl is preferable.

Representative examples of coating materials that can be used in the present invention are as follows.

Representative examples of enteric coatings include hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, cellulose acetate phthalate, shellac, methacrylic acid-methyl methacrylate copolymer, methacrylate Acid-ethyl acrylate copolymer etc. are mentioned.

The coating material of the present invention may be used in an amount of 0.2 to 20 parts by weight, preferably 0.2 to 10 parts by weight, based on 1 part by weight of cefuroxime acetyl.

(6) pharmaceutically acceptable additives

The composition for oral administration according to the present invention may be formulated into pharmaceutical formulations such as powders, dry syrups, and granules according to conventional methods, and may further include other pharmaceutically acceptable additives to aid in formulation. Representative examples of the additives include sugars such as sugars, viscosity modifiers such as gum, powder excipients that can be used in emulsifiers, pH adjusters, and other powders, and the like, and fragrances, colorants, sweeteners and the like can be further added.

Pharmaceutically acceptable additives required for formulation may be used in amounts of 0.01 to 100 parts by weight, preferably 0.02 to 50 parts by weight, based on 1 part by weight of cefuroxime axetyl.

In addition, the present invention is to prepare a granule after mixing and mixing amorphous cefuroxime axetyl solid dispersion or amorphous cefuroxime axetyl and disintegrant to a nonionic surfactant having a molten HLB range of 1 to 8 and a melting point of 35 to 80 ℃ It provides a method for producing the cefuroxime axetyl granules comprising the step of.

The method for producing cefuroxime axetyl granules of the present invention

1) heating and melting a nonionic surfactant having a HLB in the range of 1 to 8 and a melting point of 35 to 80 ° C .;

2) adding and dispersing an amorphous cefuroxime acetil solid dispersion or a mixture of amorphous cefuroxime axetyl and a disintegrant to the molten nonionic surfactant; And

3) cooling the molten mixture of step 2) and then grinding the melt mixture to a predetermined size to produce granules.

The melting temperature in step 1) is preferably from 60 to 75 ° C. In addition, by further adding and melting a nonionic surfactant of at least HLB 8 in step 1), the granules produced by the present method can be emulsified and dispersed in water stably and the release property can be enhanced. In order to use the prepared granules in the form of suspension for oral administration, in step 3), it is preferable to adjust the size of the particles to 45 to 60 mesh. Granules that do not pass through the 45 mesh screen may be further ground to increase the yield of 45 to 60 mesh particles.

The cefuroxime axetyl granules of the present invention prepared as described above are easy to take and reproducibly mask the bitter taste, exhibit excellent dissolution rate and stability, and exhibit good release properties.

Granules prepared by the above method may be coated in a conventional pharmaceutical method as necessary, or may be formulated in various forms by mixing with a pharmaceutically acceptable carrier.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

Example 1 Preparation of Sepuroxime Axetyl Granules 1

(Step 1) Preparation of Amorphous Sepuroxime Axetyl Solid Dispersion

100 parts by weight of crystalline cefuroxime axetyl and 16.63 parts by weight of Tween 80 were dissolved in acetone, and 16.63 parts by weight of silicon dioxide was added thereto and dispersed well. The dispersion was spray dried using a spray dryer under conditions of an inlet temperature of 45 ° C. and an outlet temperature of 37 ° C. to prepare a solid dispersion. The solid dispersion was dried at 30 to 40 ° C. for about 3 hours to remove residual solvent.

(Step 2) Preparation of Cepuroxime Axetyl Granules

231 g of sucrose fatty acid ester (Dai-ichi Kogyo Seiyaku), a nonionic surfactant, and 14 g of poloxamer, a nonionic surfactant, were mixed and melted by heating to about 75 ° C. 56 g of amorphous cefuroxime acetyl solid dispersion prepared in Step 1 and 231 g of alginic acid (trade name Kelasid, ISP company) as a disintegrating agent were added before cooling and completely solidified. Granulated to a size of 60 to 60 mesh. In order to improve the yield of 45-60 mesh of cefuroxime axetyl particles, the fine particles produced by grinding and processing (ie, fractions passed through a 60 mesh screen) were regranulated to finally yield 532 g.

Example 2 Preparation of Sepuroxime Axetyl Granules 2

Sepuroxime axetyl granules were prepared in the same composition and amount as in Example 1, except that amorphous cefuroxime axetyl raw material (Orchid Chemicals & Pharmaceuticals, India) was used instead of amorphous cefuroxime axetyl solid dispersion as a main component. .

Example 3 Preparation of Sepuroxime Axetyl Granules 3

Sepuroxime axetyl granules were prepared in the same composition and amount as in Example 1, except that crosslinked sodium carboxymethyl cellulose (AVEBE) was used instead of alginic acid as a disintegrant.

Example 4 Preparation of Sepuroxime Axetyl Granules 4

Sepuroxime axetyl granules were prepared in the same composition and amount as in Example 1, except that sodium starch glycolate (Penwest) was used instead of alginic acid as a disintegrant.

Example 5 Preparation of Cepuroxime Axetyl Granules 5

Sepuroxime acetyl granules were prepared in the same composition and amount as in Example 1, except that sorbitan monopalmitate (Il shin emulsifier) was used instead of sucrose fatty acid ester as a nonionic surfactant.

Example 6 Preparation of Cepuroxime Axetyl Granules 6

Sepuroxime acetyl granules were prepared in the same composition and amount as in Example 1, except that sorbitan monostearate (Il shin emulsifier) was used instead of sucrose fatty acid ester as a nonionic surfactant.

Example 7 Preparation of Cepuroxime Axetyl Granules 7

Sepuroxime acetyl granules were prepared in the same composition and amount as in Example 1 except that sorbitan tristearate (Il shin emulsifier) was used instead of sucrose fatty acid ester as a nonionic surfactant.

Example 8 Preparation of Cepuroxime Axetyl Granules 8

Sepuroxime axetyl granules were prepared in the same composition and amount as in Example 1, except that HCO-50 (NIKKOL Co., Ltd.) was used instead of poloxamer 407 as a surfactant.

Example 9 Preparation of Sepuroxime Axetyl Granules 9

Sepuroxime axetyl granules were prepared in the same composition and amount as in Example 1, except that Tween 20 (ICI) was used instead of Poloxamer 407 as a surfactant.

Example 10 Coating Preparation of Sepuroxime Axetyl Granules 1

Eudragit® L30D-55 (R ㆆ hm) 177.3 (53.2 as a solid powder) g, triacetin (Triacetin, plasticizer) for 532 g of the cefuroxime acetyl granules prepared in Example 1 A bottom spray was performed on a NQ-160 fluid bed bed of DALTON, Japan, using a coating liquid consisting of 5.32 g and 355 g of distilled water. At this time, the inlet temperature was 36 to 39 ° C, the outlet temperature was 24 to 28 ° C, the liquid injection amount was 0.7 to 0.8 ml / min, spraying air pressure (40 to 50 psi) to coat the methacrylic acid- A complex coated with Eudragit® L30D-55, a methyl methacrylate copolymer, was obtained.

Example 11 Coating Preparation of Sepuroxime Axetyl Granules 2

A coated complex was obtained in the same manner as in Example 10 except that hydroxypropyl methylcellulose phthalate (Shin-Etsu) was used as the coating material.

Example 12 Coating Preparation of Sepuroxime Axetyl Granules 3

Except for the use of Eudragit® E-100 (R ㆆ hm), a butyl methacrylate- (2-dimethylaminoethyl) methacrylate-methylmethacrylate copolymer as coating material. It carried out by the method similar to Example 10, and obtained the coated complex.

Example 13 Coating Preparation of Cepuroxime Axetyl Granules 4

A coated complex was obtained in the same manner as in Example 10 except that ethyl cellulose (IPI) was used as the coating material.

Preparation Example 1 Preparation of Dry Syrup 1

590.52 g of cefuroxime acetil coating prepared in Example 10, 660.8 g sucrose powder, 2.1 g corn starch, 14.0 g stevioside, 114.8 g tutti-frutti flavor ) Are mixed evenly. Oral dry syrup of cefuroxime axetyl was prepared by adding and mixing the remaining components, 8.4 g citric acid and 9.1 g sodium citrate.

Preparation Example 2 Preparation of Dry Syrup 2

1,181 g of the cefuroxime acetyl coating prepared in Example 11 was mixed evenly with 7 g of xanthan gum, 14 g of corn starch, 1.4 g of sodium lauryl sulfate, 7 g of methylcellulose, and 4,812 g of sucrose powder. The granules were then prepared with the addition of 355 g of silicone suspension 30% (Dow Corning, LS-300 emulsion) and dried at about 55 ° C. The oral dry syrup of cefuroxime axetyl was prepared by adding and mixing the remaining ingredients, 284 g of cidar fragrance powder, 284 g of drink fragrance powder, 71 g of citric acid, and 43 g of sodium citrate.

Test Example 1 Stability Test in Aqueous Solution

The preparation of cefuroxime axetyl prepared by the method of Formulation Example 2 and GSK's Jinnet (Zinnat®) dry syrup was suspended in 5 ml purified water at 150 mg equivalent amount as cepuroxime axetyl, respectively. Each suspension was left at room temperature and released into purified water of cefuroxime axetyl on day 1, day 2, day 4 and day 6 to confirm the amount dissolved by UV detector. At this time, the analysis was carried out at a wavelength of 278 nm, the emission amount (%) was a total content of 100% and after a certain period of time to measure the emission amount emitted from it was recorded as a relative value.

As a result, as shown in Figure 1, the cefuroxime axetyl preparation according to the present invention was stable above the control in the storage conditions that the patients actually take. In addition, it can be seen that it is suitable for the preparation of cefuroxime axetyl, which is unstable in an aqueous state because of no change in taste due to high stability.

Test Example 2 Dissolution Test in Phosphate Buffer

A comparative dissolution test of cefuroxime acetyl prepared by the method of Formulation Example 1 and GSK's Jinnet (Zinnat®) dry syrup as a cefuroxime axetyl, respectively, was carried out in an amount equivalent to 150 mg. At this time, 900 ml of 0.05 mol / L potassium dihydrogen phosphate buffer (pH 7.0) was used as the eluent, and it was carried out as described in Method 2 of the Korean seventh tablet dissolution test method at 100 rpm at 37 ± 0.5 ° C. It was.

The eluate obtained therefrom was analyzed at 278 nm wavelength using a UV detector.

As a result, as shown in Figure 2, the cefuroxime axetyl preparation according to the present invention showed a good dissolution properties similar to the control.

<Test Example 3> Bitter taste shielding effect test

Sepuration of cefuroxime acetyl prepared by the method of Formulation Examples 1 and 2 and GSK's Jinnet (Zinnat®) dry syrup as 150 mg of cefuroxime acetil, respectively, as a control to confirm the bitter taste shielding effect The sensory test was performed.

Specifically, the formulation of Formulation Example 1, Formulation Example 2 Formulation and Jinnet dry syrup was suspended by adding 5 mL of purified water to 150 mg equivalent amount as cepuroxime axetyl. Five syrups of 20-30 year-old adult men and women were placed in the mouth for 10 seconds, and immediately after spitting, the strength of Gomi was evaluated as the initial Komi strength, and after 1 minute, the Komi strength was regarded as the latter. Shown in

A person who expressed the bitter taste was evaluated as A when 2 or less, B when 3 to 5, C when 6 to 8, and D when 9 to 10.

Early high tail strength Late high Komi strength Formulation Example 1 A A Formulation Example 2 A A Ginnet (registered trademark) A C

From the results in Table 1, it can be seen that the formulations of the present invention exhibit lower gourd than the control formulation.

Test Example 4 Animal Experiment for Evaluating Bioavailability

GSK's Jinnet (Zinnat®) dry syrup was prepared as a cefuroxime axetyl in rats at 20 mg / kg, respectively, as a preparation of cefuroxime axetyl prepared by the method of Formulation Example 1 and as a control. Rats used SD and when administered, the formulation was dispersed in 2 ml of water and orally administered using oral sonde. After administration, a certain amount of blood was collected after 30, 60, 120, 180, 300, 420 minutes, and the method of J. Kor. Pharm. Sci., Vol. 29, No. 4, 361-365 (1999). The sample was pretreated according to the procedure. This blood sample was analyzed by liquid chromatography according to the method of the document. 50 μl at a flow rate of 1.0 ml / min using Inertsil ODS-2 (4.6 × 250 mm) C ₁₈ as the column, 0.05 M ammonium phosphate buffer (pH 3.2): acetonitrile (86:14) as the mobile phase Each injection was analyzed with a UV detector at 280 nm wavelength.

As a result, as shown in Figure 3 and Table 2, the preparation for cefuroxime axetyl dry syrup according to the present invention showed a higher bioavailability than the control formulation.

AUC7h (μg.hr / ml) ^{* 1} T _max (hr) ^{* 2} C _max (μg / ml) ^{* 3} Formulation Example 1 11.3 ± 2.5 1.0 ± 0.0 3.7 ± 0.3 Ginnet (registered trademark) 7.3 ± 2.5 1.0 ± 0.0 2.9 ± 1.1  * 1: Area under the plasma concentration curve of the drug up to 7 hours after administration * 2: Time to peak plasma concentration * 3: Maximum plasma concentration

As described above, the cefuroxime axetyl granules of the present invention are excellent in the stability of the drug and effectively masked the bitter taste, showing improved medication compliance and reproducible production.

Claims (10)

Amorphous cefuroxime axetyl solid dispersion or amorphous cefuroxime axetyl; Sucrose fatty acid esters, sorbitan fatty acid esters and propylene glycol fatty acid esters selected from the group consisting of propylene glycol fatty acid esters, HLB ranges from 1 to 8 and has a melting point Nonionic surfactants between 35 and 80 ° C .; And cefuroxime axetyl granules prepared by mixing and melting a disintegrant. delete The method of claim 1, The disintegrant is selected from the group consisting of microcrystalline cellulose, crosslinked sodium carboxymethyl cellulose, crosslinked polyvinyl pyrrolidone, ion exchange resins, alginic acid and sodium starch glycolate. Sepuroxime Axetyl Granules. The method of claim 1, 1 to 20 parts by weight of a nonionic surfactant having an HLB in the range of 1 to 8 and a melting point of 35 to 80 ° C, and 0.2 to 20 parts by weight of a disintegrant, based on 1 part by weight of the amorphous cefuroxime axetyl solid dispersion or amorphous cefuroxime axetyl Sepuroxime axetyl granules, characterized in that it comprises a. The method of claim 1, Sepuroxime axetyl granules further comprising a coating material and a pharmaceutically acceptable additive. The method of claim 5, wherein Sepuroxime axetyl granules, characterized in that the coating material is an enteric coating material. The method of claim 5, wherein A cefuroxime acetyl granules comprising from 0.2 to 10 parts by weight of a coating material and from 0.02 to 50 parts by weight of a pharmaceutically acceptable additive with respect to 1 part by weight of amorphous cefuroxime axetyl solid dispersion or amorphous cefuroxime axetyl. 1) HLB is selected from the group consisting of sucrose fatty acid esters, sorbitan fatty acid esters and propylene glycol fatty acid esters and has a HLB ranging from 1 to 8 Applying heat to a nonionic surfactant having a melting point of 35 to 80 ° C. to melt; 2) adding and dispersing an amorphous cefuroxime axetyl solid dispersion or a mixture of amorphous cefuroxime axetyl and a disintegrant to the molten surfactant of step 1); And 3) cooling the melt mixture of step 2) and then pulverizing it to a constant size to produce granules. delete The method of claim 8, Melting temperature in step 1) is 60 to 75 ℃.

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