KR20060092375A - A pellet agent containing clarithromycin for oral suspension - Google Patents

Abstract

The present invention relates to a pellet preparation for clarithromycin-containing syrup that masks the bitterness of clarithromycin, and more particularly, lactose, non-pareil, lactose-crystalline cellulose (trade name, MicroceLac 100), and sucrose, which are inert cores. Clarithromycin in the size of 180 to 350 μm, methacrylic acid-methylmethacrylate copolymer as enteric coating polymer, trialkyl citrate as a plasticizer, glycerol fatty acid derivative, dialkyl sebacate, oleate, ditriacetin, A first drug-containing layer is prepared by coating one or two or more mixtures selected from dialkyl phthalate and castor oil, followed by second coating of sodium alginate or propylene glycol having excellent resistance to acids, followed by final enteric coating. In a dry syrup formulation for oral administration comprising a clarithromycin pellet shielded in the multi-layer coating method It is about.

Macrolide antibiotics, clarithromycin, multilayer pellets, finely inert cores, bitter taste masking, enteric coatings, plasticizers

Description

A Pellet Agent Containing Clarithromycin for oral suspension}

1 illustrates a coating layer formed on a clarithromycin pellet formulation consisting of a multilayer coating.

The present invention relates to a pellet preparation for clarithromycin-containing syrup that masks the bitter taste of clarithromycin, a macrolide antibiotic, and specifically, has a primary coating layer containing an effective drug on the outside of an inert core, and has acid resistance. It relates to a formulation for orally administering clarithromycin pellets comprising a multilayer coating layer such as a secondary coating layer and a tertiary coating layer forming an enteric coating layer.

Clarisomycin refers to 6-O-methylerythromycin and is a macrolide antibiotic. Clarithromycin is known as S. pyogenes , S. pneumoniae , S. agalactiae , Streptococcus viridans , M. catarrhalis , Clidi . Mia trachomatis (C. trachomatis), Large ohnel LA (Legionella) Acute exacerbation of sore throat, tonsillitis, acute maxillary sinusitis, chronic bronchitis, pneumonia with antimicrobial effect against species , Mycoplasma pneumoniae ( H. influenzae ) , S. aureu s It is also used in the treatment of skin infections without complications, etc. In addition, it is used in combination with other antibiotics to eradicate H. pylori in gastric ulcer treatment. Unlike these, they are known to have excellent therapeutic effects because they are stable in the gastrointestinal tract, and azithromycin, similar to clarithromycin, is a microlide antibiotic.

The method of taking clarythromycin is usually taken orally. However, because of the bitter taste of clarithromycin itself, not only the bitter taste is felt in the mouth when taken orally, and patients with reflux esophagitis may have a bitter taste even when the drug is refluxed, there is a problem in patients compliance with the medication.

In order to solve this problem, various methods have been studied.

Korean Patent Laid-Open Publication No. 2002-16069 discloses a method for preparing a cation exchange resin complex by reacting in a solvent using a cation exchange resin and then drying to mask the bitter taste of the macrolide antibiotic. However, the method of the patent has a problem that it is difficult to prepare oral preparations containing the dosage of conventional macrolide antibiotics by obtaining a complex compound having a low workaround and a low content of macrolide antibiotics.

Korean Patent Publication No. 1999-67265 discloses a method of preparing granules by mixing with an anionic polymer carbomer to mask the bitter taste of macrolide antibiotics, followed by wetting and blending. However, the method of the patent is difficult to uniformly mix the drug and the water-swellable carbomer, it is required to go through repeated wet granulation process to reduce the amount of fine powder, and the manufacturing process, such as the setting of the temperature of the reaction zone, in particular the setting of the reaction temperature It is complicated and also has the disadvantage of yield problems and clarithromycin fine powder in the process of grinding using a fluidized bed grinder to produce the granules of a uniform size.

Korean Patent Registration No. 10-218700 is prepared by mixing a sugar alcohol and a basic oxide in a complex in which a basic drug having an unpleasant taste is mixed with a functional polymer, and then dispersed or dissolved in a low melting point material having a melting point of 40 to 120 ° C. A method is disclosed. However, since the method of the patent requires heat to be applied above a certain temperature in order to dissolve in a material having a low melting point, macrolide-based drugs are easily destroyed, and a macrolide-based antibiotic content is obtained. The disadvantage is that the preparation of oral formulations comprising dosages of antibiotics is difficult. In addition, a fluidized bed coater is used as a method for preparing pellets. When the size of the inert core material is too small (180 μm or less), the coating liquid is not coated on the inert core well, and the solid content of the coating liquid tends to be finely divided. Therefore, in the case of a general sustained release pellet preparation or pellet preparation, an inert core of 300 μm or more is used.

As described above, the method for preparing the macrolide antibiotic disclosed in the present invention requires a complicated manufacturing process to block bitter taste.

The present invention is to provide a dry syrup preparation containing a pellet for oral administration minimized foreign object by providing a fine pellet masked bitter taste of the macrolide antibiotics to solve the difficulties of the production.

It is an object of the present invention to provide a pellet formulation for clarithromycin-containing syrup that masks the bitter taste of clarithromycin.

According to the present invention, lactose, non-pareil, lactose-crystalline cellulose (trade name, MicroceLac 100), sucrose, and the like are used for various coating conditions using a fluidized bed coater for coating on a fine inert core having a particle size of 180 to 350 μm. The change to the branch solves the problem occurring in the conventional fine pellet coating. Specifically, according to the present invention, the primary coating solution coated on the inert core is clarithromycin, methacrylic acid-methylmethacrylate copolymer as enteric coating polymer, trialkyl citrate as plasticizer, glycerol fatty acid derivative, dialkyl One or two or more selected from sebacate, oleate, ditriacetin, dialkyl phthalate and castor oil are mixed and coated to prepare a primary drug-containing layer, and the second coating is sodium alginate having excellent acid resistance. Or dry syrup for oral administration comprising propylene glycol alginate and containing clarithromycin pellets with a bitter taste masked by a multilayer coating method such as tertiary coating.

 According to the present invention pellets having a size of 400 μm or less are prepared using lactose, nonpareil, lactose-crystalline cellulose (trade name, MicroceLac 100) or an inert core of 180 to 350 μm, preferably 180 to 200 μm, of white sugar. . The pellets prepared in this way can be easily dispersed in a dry syrup, and foreign substances can be minimized upon oral administration.

Such a pellet preparation in the form of clarithromycin dry syrup according to the present invention is described in detail below.

According to a preferred embodiment of the present invention for achieving the object, oral administration of the pellet formulation containing clarithromycin 1 containing the glaristhromycin as an effective drug outside the inert core of the size of 180 ~ 350㎛ It may include a multilayer coating layer comprising a secondary coating layer, a secondary coating layer containing sodium alginate having acid resistance and a tertiary enteric coating layer.

According to another suitable embodiment of the present invention, the inert core is one to two or more mixtures selected from white sugar, lactose, microcrystalline cellulose, lactose-microcrystalline cellulose and dextrin, 20 to 50% by weight of the total pellet weight Can be.

According to another suitable embodiment of the present invention, the effective drugs clarithromycin and azithromycin may be 20 to 50% by weight relative to the total pellet weight.

According to another suitable embodiment of the present invention, said first coating layer or tertiary coating layer comprises an enteric polymer, said enteric polymer is shellac, polyvinylacetate, Eudragit L, which is a methacrylic acid-methyl methacrylate copolymer, At least one material selected from S or a mixture of L and S, hydroxypropylmethylcellulose phthalate and cellulose acetate phthalate may be from 5 to 30% by weight relative to the total pellets.

According to another suitable embodiment of the present invention, the sodium alginate of the secondary coating layer may be 3 to 8% by weight based on the weight of the primary coating pellets.

According to another suitable embodiment of the present invention, the primary coating layer or the tertiary coating layer comprises a plasticizer, and the plasticizer is triethyl citrate, tributy citrate, acetyl citrate, acetyl buty citrate Selected from trialkyl citrate, glycerol bihenate, glycerol fatty acid derivatives of glycerol distearate, dibutyl phthalate, diethyl phthalate and dialkyl phthalate of dimethyl phthalate. And 2 to 10% by weight of the total pellets.

According to another suitable embodiment of the present invention, there is provided a dry syrup for oral administration comprising the pellet formulation set forth above.

According to another suitable embodiment of the present invention the syrup may comprise a sweetener, preservative, flavoring agent, thickener, pH adjuster or suspending agent.

The invention is described in detail below by way of example and not by way of limitation.

1 shows a coating form of a pellet formulation of clarithromycin dry syrup having a multi-layer coating according to the present invention.

As shown in Figure 1, the pellet preparation according to the present invention is an inert core, a primary coating layer containing the clarithromycin active drug coated on the core, a secondary coating layer having an acid resistance and a tertiary coating layer consisting of an enteric coating layer It includes. Each coating layer is formed by the following method.

(1) inert core and primary coating layer

The primary coating is formed on the outside of the insoluble core with a coating layer containing clarithromycin, an effective drug.

The composition ratio of the inert core and the primary coating layer is 20 to 50% by weight, 20 to 50% by weight of clarithromycin, and 5 to 30% by weight of methacrylic acid-methylmethacrylate copolymer as an enteric coating polymer. %, 1 to 5% by weight of a base selected from trialkyl citrate, glycerol fatty acid derivatives, dialkyl sebacate, oleate, ditriacetin, dialkyl phthalate, castor oil, and the like as a plasticizer. As for the particle diameter of the said inert core, 180-350 micrometers is suitable, Preferably it is 180-200 micrometers. The inert core of 180 μm or less has a small amount of coating due to the large loss of solids of the coating liquid. In the case of an inert core of 350 μm or more, the size of the final pellet is large, and foreign substances may occur in the mouth during oral administration. The methacrylic acid-methylmethacrylate copolymer as coating polymer for enteric coating has a low viscosity due to the low viscosity of the coating solution when it is less than 5% by weight, and the viscosity increases when more than 30% by weight is used for coating. Pellet sticks to it. In addition, in the present invention, the material that can be used as the inert core may be white sugar, lactose, microcrystalline cellulose, lactose-crystalline cellulose (MicroceLac 100) or dextrin.

(2) secondary coating: coating of alginic acid with excellent acid resistance

A process for coating alginic acid with excellent acid resistance on primary coated pellets. After dissolving sodium alginate in a solvent with a volume ratio of purified water and acetone of 80: 20 to 95: 5 in an amount of 1 to 4% by weight based on the weight of the solvent, the first step 3 to 8% by weight based on the weight of the coating pellets. As a solvent used for coating, the ratio of purified water and acetone is preferably 90:10, and when the ratio of acetone is increased, sodium alginate may be precipitated. Therefore, aceted amounts of the indicated amounts are preferred.

(3) 3rd coating: enteric coating

Enteric coating on pellets coated in secondary is a solvent mixture of acetone, purified water and ethanol in a ratio of 4.5 to 5.2: 0.4 to 0.8: 4.5 to 5.2 and enteric coating material methacrylic acid- methyl methacrylate copolymer Is dissolved 4 to 6% by weight of the solvent, and one or two or more mixtures selected from trialkyl citrate, glycerol fatty acid derivatives, sebacic acid fatty acid esters and castor oil as a plasticizer is methacrylic coating material It can be used in 1 to 30% by weight relative to the weight of the acid-methyl methacrylate copolymer. This coating solution is coated to 20 to 60% by weight relative to the secondary coated pellets.

In the case of coatings according to the invention, plasticizers are typically pharmaceutically acceptable plasticizers such as trialkylcitrate, glycerol fatty acid derivatives, dialkyl sebacates, dialkyloleates, ditriacetin, dialkylphthalates or castor oils. Trialkyl citrate may play an important role in masking bitter taste of triethyl citrate, tributyl citrate, acetyl triethyl citrate or acetyl tributyl citrate. Glycerol bihenate or glycerol distearate may be used as the glycerol fatty acid derivative. Dialkyl phthalates include dibutyl phthalate, diethyl phthalate, dimethyl phthalate and the like. The plasticizer may be used in the range of 5 to 30% by weight of the polymer to be coated. If the plasticizer is less than 5% by weight, the coated polymer film is very brittle, and cracking occurs due to moisture, which promotes the release of the effective drug, whereas if it is more than 30% by weight, the coated polymer cannot be formed into a film. There is.

As the most suitable plasticizer in the present invention, a fat-soluble plasticizer is suitable, and as the fat solubility is increased, the effect of delaying the release of the effective drug appears.

When prepared in accordance with the present invention orally administered clarithromycin dry syrup, it is preferable to contain 20 to 50% by weight of clarithromycin relative to the total pellet weight. When clarithromycin is less than 20% by weight of the total weight of the formulation, the main ingredient of the pellet is low, and when the syrup is used, a large amount of pellet is contained, so the amount of additives such as sweetener is limited. The size of the filament is so large that foreign bodies appear when administered orally.

In the present invention, in order to effectively mask the bitter taste, it is preferable to use an enteric coating material, the content of the enteric coating material is preferably 20 to 50% by weight relative to the total pellet formulation weight. If the enteric coating material is included in less than 20% by weight of the total pellet weight, satisfactory bitterness shielding effect is not obtained, and when it is included in excess of 50% by weight, it is not preferable because it can suppress the release of the main drug clarithromycin.

In the embodiment according to the present invention in the coating process, a peristaltic pump having a silicon tube (inner diameter: 6.0 mm) was used as the fluidizing coating machine of the GPCG type, and the coating liquid was sprayed at about 5 g per minute, and the injection pressure was 1.2. adjusted to bar. A, B or C type was used as the type of air dispersion plate, and the amount of air sprayed was adjusted to 15%. The chamber to be sprayed along the air stream was preheated. It was fluidized by addition of an inert core, and then clarithromycin was sequentially coated by the primary, secondary and tertiary coating methods. The temperature of each process product was 34-36 degreeC, and the flow rate at the time of coating was adjusted so that it might be 5 m / sec.

The orally administered clarithromycin dry syrup of the present invention is suitably mixed with an appropriate amount of sweetener, preservative, flavoring agent, thickener, pH adjuster and suspending agent in the clarithromycin fine pellet coated with enteric polymer and acid resistant sodium alginate. Each component may be prepared as a dry syrup uniformly blended.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to the above Examples.

Example 1

Primary coating: manufacturing effective drug layer

First, 150 g of MicroceLac of 180 to 350 µm as an inert core was fluidized in a fluidized bed coater, and then 150 g of clarithromycin as a main component, 60 g of hydroxypropyl methyl cellulose phthalate and 6 g of triacetin as an enteric coating material were used. Methylene: Ethanol = 1: 1 Completely dissolve in 3,000 g of mixed solvent and spray to coat the active drug layer. However, the operating conditions of the fluidized bed coater is shown in Table 1 below.

Table 1: Fluidized Bed Coating Machine Operating Conditions

Inlet air temperature 60 ℃ Product bed temperature 35 ℃ Feeding rate 5 g / min Air flap 10% Spray nozzle pressure 1.2 bar Spray nozzle diameter 0.8 mm Dispersion plate type B type

Second coating: Coating of sodium alginate layer with excellent acid resistance

The main component coating was completed in the same manner as described above, and 5 wt% of the primary coating pellet was coated with sodium alginate. However, the operating conditions of the fluidized bed coater was made according to the conditions of Table 1.

3rd coating: enteric coating

To 300 g of secondary coated pellets, 120 g of Eudragit S 100 as an enteric polymer, and 12 g of triethyl citrate (TEC) as a plasticizer were mixed with acetone: ethanol: purified water = 0.47: 0.47: 0.6. After complete dissolution in 2,400 g, the coating was sprayed onto a clarithromycin pellet in which the water-insoluble coating was completed. However, the operating conditions of the fluidized bed coater were in accordance with the conditions of Table 1 above.

Example 2

Primary coating: manufacture of effective drug layer

First, 150 g of MicroceLac of 180 to 350 μm as an inert core was fluidized in a fluidized bed coater, and then 150 g of clarithromycin, the main component, 60 g of Eudragit L and 10 g of glycerol bihenate were used as an enteric coating material. : Ethanol = 1: 1 Completely dissolved in 3,000 g of mixed solvent and sprayed to coat the effective drug layer. However, the operating conditions of the fluidized bed coater was as shown in Table 1 above.

Secondary coating: Coating of sodium alginate layer with excellent acid resistance

When the main component coating was completed, it was coated with sodium alginate 5% by weight based on the weight of the primary coating pellets. However, the operating conditions of the fluidized bed coater was made according to the conditions of Table 1.

3rd coating: enteric coating

In 300 g of secondary coated pellets, 120 g of Eudragit S 100 (Eudragit S 100) as an enteric polymer and 12 g of triethyl citrate (TEC) as a plasticizer were added in acetone: ethanol: purified water = 0.47: 0.47: 0.6 mixed solvent. After complete dissolution in 2,400 g, the coating was sprayed onto a clarithromycin pellet in which the water-insoluble coating was completed. However, the operating conditions of the fluidized bed coater followed the conditions of Table 1 above.

Example 3

Primary coating: manufacture of active drug layer

First, 150 g of MicroceLac of 180 to 350 μm as an inert core was fluidized in a fluidized bed coater, followed by 150 g of clarithromycin as the main component, 60 g of Eudragit S and 10 g of glycerol bihenate as an enteric coating material. Ethanol = 1: 1 dissolved completely in 3,000 g of mixed solvent and then sprayed to coat the effective drug layer. However, the operating conditions of the fluidized bed coater was the same as in Table 1 above.

Secondary coating: Coating of sodium alginate layer with excellent acid resistance

When the main component coating was completed, it was subjected to 2% by weight based on the weight of the primary coating pellets with sodium alginate. However, the operating conditions of the fluidized bed coater followed the conditions of Table 1 above.

3rd coating: enteric coating

To 300 g of secondary coated pellets, 120 g of Eudragit S 100 as an enteric polymer, and 12 g of triethyl citrate (TEC) as a plasticizer were mixed with acetone: ethanol: purified water = 0.47: 0.47: 0.6. After complete dissolution in 2,400 g, the coating was sprayed onto a clarithromycin pellet in which the water-insoluble coating was completed. However, the operating conditions of the fluidized bed coater followed the conditions of Table 1 above.

The following examples are shown in Tables 2 and 3 the amount of the effective drug and the additives to coat in the same manner as in Examples 1, 2, and 3.

Table 2: Examples 5-7

Example 5 Example 6 Example 7 Primary coating  MicroceLac, 150 g  MicroceLac, 150 g  MicroceLac, 150 g  Clarithromycin, 150 g  Clarithromycin, 150 g  Clarithromycin, 150 g  Eudragit S 100, 60 g  Eudragit S 100, 60 g  Eudragit S 100, 60 g  Dibutyphthalate, 6 g  Dibutyphthalate, 6 g  Dibutyphthalate, 6 g Second coating: Sodium alginate coating  Sodium Alginate, 18.3 g  Sodium Alkynate, 18.3 g  Sodium Alginate, 18.3 g 3rd coating  Eudragit S 100, 120 g  Eudragit S 100, 120 g  Eudragit S 100, 120 g  Dibutyphthalate, 12 g  Glycerol Bihenate, 12 g  Glycerol Distearate, 12 g

Table 3: Examples 8-10

Example 8 Example 9 Example 10 Primary coating  MicroceLac, 150 g  MicroceLac, 150 g  MicroceLac, 150 g  Clarithromycin, 150 g  Clarithromycin, 150 g  Clarithromycin, 150 g  Eudragit S 100, 60 g  Eudragit S 100, 60 g  Eudragit S 100, 60 g  Glycerol Bihenate, 12 g  Daiquet Sebacate, 12 g  Acetyl Tributyl Citrate, 12 g Second coating: Sodium alginate coating (omitted) 3rd coating  Eudragit S 100, 120 g  Eudragit S 100, 120 g  Eudragit S 100, 120 g  Daiquet Sebacate, 12 g  Daiquet Sebacate, 12 g  Acetyl Tributyl Citrate, 12 g

Example 11

The active drug of Example 9 was coated with azithromycin in place of clarithromycin with the effective drug by the method of multilayer coating.

Comparative Example 1

In Comparative Example 1, clarithromycin without a coating was used.

Preparation of Dry Syrup for Application

Preparation of Clarisomycin-containing Syrup

Clarisomycin-containing syrups were prepared using the clarithromycin pellets of Examples 1 to 10 and the uncoated clarithromycin of Comparative Example 1 and are presented in Tables 5 and 6. Each composition is the amount of each component in 100 g of the total weight, and about 70 g of the syrup is prepared, and purified water is added thereto to prepare a total volume of 100 ml.

Table 5: Composition ratios of the pellet-containing syrups of Examples 1 to 10

ingredient Usage (g) weight% Clarithromycin Pellets (Examples 1 to 10) 11.786 11.786 White sugar 68.720 68.720 Strawberry flavored cotton 10.000 10.000 Xanthan gum 0.186 0.186 Potassium Sorbate 0.568 0.568 Sodium Lauryl Sulfate 0.020 0.020 Citric acid 0.430 0.430 Sodium citrate 1.290 1.290 Silicon dioxide 7.000 7.000 system 100.000 100.000

11.786 g of pellets corresponds to 3.547 g of clarithromycin.

Table 6: Composition ratio of the pellet-containing syrup of Comparative Example 1

ingredient Usage (g) weight% Clarithromycin (Comparative Example 1) 3.547 3.547 White sugar 76.959 76.959 Orange micron 10.000 10.000 Xanthan gum 0.186 0.186 Potassium Sorbate 0.568 0.568 Sodium Lauryl Sulfate 0.020 0.020 Citric acid 0.430 0.430 Sodium citrate 1.290 1.290 Silicon dioxide 7.000 7.000 system 100.000 100.000

Test Example 1

Evaluation of Bitter Taste of Clarisomycin-containing Dry Syrup

The clarithromycin-containing dry syrup prepared according to Formulation Example 1 was orally administered to 10 healthy adults, and the bitter taste was evaluated 5 minutes after administration. Evaluation criteria were evaluated by the following six grades. The test results are shown in Table 4 below.

0: It does not feel bitter taste at all. 1: 쓴 has a bitter taste.

2: Write a little. 3: Writing.

4: Use but withstand. 5: I can't stand it.

Table 7: Test results for bitterness

quite Bitter taste Comparative Example 1 5 Example 1 4 Example 2 3 Example 3 3 Example 4 3 Example 5 2 Example 6 One Example 7 One Example 8 0 Example 9 0  Example 10 0  Example 11 0

Looking at the results of Examples 1 to 11 of Table 7, it can be seen that the more the fat-soluble plasticizer, the bitter taste shielding effect of clarithromycin.

Multilayer formed according to the present invention with an inert core coated with methacrylic acid-methylmethacrylate copolymer and plasticizer as the primary effective drug, clarithromycin, an enteric polymer, secondary sodium alginate, and tertiary enteric coating and plasticizer The pellet is provided with an orally administered clarithromycin dry syrup that masks the bitter taste of clarithromycin.

The dry syrup according to the present invention does not exhibit a strong bitter taste when taken and enables the preparation of a pellet formulation for clarithromycin-containing syrup that can dramatically block the reflux of bitter taste even when administered to a patient with reflux esophagitis. In particular, it has the effect of increasing the treatment effect by increasing the ease of taking and medication compliance of infants and infants should choose a syrup formulation.

Claims (8)

In the pellet preparation for oral administration containing clarithromycin, A multi-layer coating layer comprising a primary coating layer containing the glaris mycin as an effective drug, a secondary coating layer containing an acid-resistant sodium alginate, and a tertiary enteric coating layer outside of an inert core having a size of 180 to 350 μm. Clarisomycin-containing pellet formulation for oral administration comprising a. The method according to claim 1, wherein the inert core is one to two or more selected from the group consisting of white sugar, lactose, microcrystalline cellulose, lactose-crystalline cellulose and dextrin, 20 to 50% by weight of the total pellet weight, characterized in that Clarithromycin-containing pellet preparation for oral administration. The method of claim 1, wherein the effective drug clarithromycin or azithromycin is 20 to 50% by weight relative to the total pellet weight of the orally administered clarithromycin pellet preparation. The method according to claim 1, wherein the first coating or tertiary coating layer comprises an enteric polymer, wherein the enteric polymer of Eudragit L, S or L and S of the shellac, polyvinylacetate, methacrylic acid- methyl methacrylate copolymer A mixture of hydroxypropyl methyl cellulose phthalate and cellulose acetate phthalate is one or more selected from the group consisting of 5 to 30% by weight of the total pellet, characterized in that the orally administered clarithromycin containing pellet formulation. The method of claim 1, wherein the sodium alginate of the secondary coating layer is clarithromycin pellet formulation for oral administration, characterized in that 3 to 8% by weight based on the weight of the primary coating pellets. The method of claim 1, wherein the primary coating layer or the tertiary coating layer comprises a plasticizer, the plasticizer triethyl citrate, tributy citrate, acetyl citrate, trialkyl citrate of acetyl buty citrate Or glycerol fatty acid derivatives of glycerol bihenate, glycerol distearate, dibutyl phthalate, diethyl phthalate and dialkyl phthalate of dimethyl phthalate. Clarithromycin pellet preparation for oral administration, characterized in that 30% by weight. Dry syrup for oral administration comprising the pellet preparation of any one of claims 1 to 6. 8. The dry syrup for oral administration according to claim 7, comprising a sweetener, preservative, flavoring agent, thickener, pH adjuster or suspending agent.

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