Tebipenem pivoxil granule and preparation method thereof

Abstract

The invention provides a tipipenem pectin granule and a preparation method thereof, and relates to the technical field of medicine and its preparation. A tipipenem granule, comprising the following raw materials in parts by weight: 600 to 700 parts of tipipenem, 3500 to 4500 parts of diluent, 40 to 50 parts of hydroxypropyl cellulose, and 455 to 470 parts of coating agent I 380-400 parts of coating agent II, the coating agent I is composed of ethyl cellulose suspension and talcum powder at a weight ratio of 10-20:1, the coating agent II is composed of gastric-soluble acrylic resin, Talc powder, hydroxypropyl methylcellulose and aspartame are composed in a weight ratio of 25-40:1-3:1:1.5-2.5. The tipipenem ester granule of the present invention uses tipipenem ester as the main drug, strictly screens and controls the ingredients of the excipients, optimizes the proportion, has stable drug efficacy under high temperature and high humidity environment, safe quality, high dissolution rate and excellent process. Easy to control and suitable for industrial production.

Description

Technical field

[0001] The invention relates to the technical field of medicines and their preparation, in particular to a granule of tipipenem ester and a preparation method thereof. Background technique

[0002] Tippenem ester ( Tebipenempivoxil ) Is a new broad-spectrum antibiotic of oral penem. It was originally researched and developed by Wyeth Rieter Co., Ltd., and then transferred to Meiji Confectionery Pharmaceutical Co., Ltd. in Japan in March 2002. It was approved by the Ministry of Health and Welfare in Japan in April 2009. It was first launched in Japan on 26th. Tippenem ester, chemical name is (1R, 5S, 6S)-6-[1(R)-hydroxyethyl]-1-methyl-2-[1-(2-thiazolin-2-yl) Azetidine-3-ylthio]-1-carbapenem-2-ene-3-carboxylic acid pivaloyloxymethyl ester, its chemical structure is: , The molecular formula is: C 22 H 31 N 3 O 6 S 2 .

[0003] The structural feature of Tippenem Ester is that the C3 side chain is a thiazolyl substituted azetidinyl group, and the prodrug is formed by ...

Examples

Embodiment 1

[0035] The formula of Tippenem Methoxylate Granules is as follows:

[0036] Raw materials

Dosage g

Ratio w / w%

Tippenem

655

11.80

Microcrystalline cellulose

1000

18.02

sucrose

3000

54.05

Hydroxypropyl cellulose

45

0.81

talcum powder

49.3

0.89

Ethyl cellulose suspension

433

7.80

Hydroxypropylmethylcellulose

10.3

0.19

Aspartame

18.5

0.33

Ethyl acrylate-methyl methacrylate copolymer water dispersion

339

6.11

[0037] Refer to figure 1 , The preparation method of tippenem meximate granules includes the following steps:

[0038] Step S1: prepare a hydroxypropyl cellulose solution, mix the hydroxypropyl cellulose with pure water, and stir to prepare a solution with a mass percentage of 2 wt%; respectively prepare coating agent I and coating agent II into solutions for use;

[0039] Step S2: Pass the tipipenem ester and diluent through a 100-mesh sieve, weigh the formulated amount of tipipenem ester, microcrystalline cellulose and sucrose, and add them to the fluidized bed granulation...

Embodiment 2

[0047] The formula of Tippenem Methoxylate Granules is as follows:

[0048] Raw materials

Dosage g

Ratio w / w%

Tippenem

655

11.80

Microcrystalline cellulose

1000

18.02

sucrose

3000

54.05

Hydroxypropyl cellulose

45

0.81

talcum powder

49.3

0.89

Ethyl cellulose suspension

433

7.80

Hydroxypropylmethylcellulose

10.3

0.19

Aspartame

18.5

0.33

Ethyl acrylate-methyl methacrylate copolymer water dispersion

339

6.11

[0049] The preparation method of Tippenem Methoxylate granules includes the following steps:

[0050] Step S1: Prepare a hydroxypropyl cellulose solution, mix the hydroxypropyl cellulose with pure water, and stir to prepare a solution with a mass percentage of 2 wt%; respectively prepare coating agent I and coating agent II into solutions, see implementation Example 1, spare;

[0051] Step S2: Pass the tipipenem ester and diluent through a 120-mesh sieve, weigh the formula amount of tipipenem ester, microcrystalline cellulose and sucrose, add them to the fluidized bed granul...

Embodiment 3

[0057] The formula of Tippenem Methoxylate Granules is as follows:

[0058] Raw materials

Dosage g

Ratio w / w%

Tippenem

655

11.80

Microcrystalline cellulose

1000

18.02

sucrose

3000

54.05

Hydroxypropyl cellulose

45

0.81

talcum powder

49.3

0.89

Ethyl cellulose suspension

433

7.80

Hydroxypropylmethylcellulose

10.3

0.19

Aspartame

18.5

0.33

Ethyl acrylate-methyl methacrylate copolymer water dispersion

339

6.11

[0059] The preparation method of Tippenem Methoxylate granules includes the following steps:

[0060] Step S1: Prepare a hydroxypropyl cellulose solution, mix the hydroxypropyl cellulose with pure water, and stir to prepare a solution with a mass percentage of 2 wt%; respectively prepare coating agent I and coating agent II into solutions, see implementation Example 1, spare;

[0061] Step S2: Pass the tipipenem ester and diluent through a 200-mesh sieve, weigh the formula amount of tipipenem ester, microcrystalline cellulose and sucrose, add them to the fluidized bed granul...

Technical field

[0001] The invention relates to the technical field of medicines and their preparation, in particular to a granule of tipipenem ester and a preparation method thereof. Background technique

[0002] Tippenem ester ( Tebipenempivoxil ) Is a new broad-spectrum antibiotic of oral penem. It was originally researched and developed by Wyeth Rieter Co., Ltd., and then transferred to Meiji Confectionery Pharmaceutical Co., Ltd. in Japan in March 2002. It was approved by the Ministry of Health and Welfare in Japan in April 2009. It was first launched in Japan on 26th. Tippenem ester, chemical name is (1R, 5S, 6S)-6-[1(R)-hydroxyethyl]-1-methyl-2-[1-(2-thiazolin-2-yl) Azetidine-3-ylthio]-1-carbapenem-2-ene-3-carboxylic acid pivaloyloxymethyl ester, its chemical structure is: , The molecular formula is: C 22 H 31 N 3 O 6 S 2 .

[0003] The structural feature of Tippenem Ester is that the C3 side chain is a thiazolyl substituted azetidinyl group, and the prodrug is formed by ...

Examples

Embodiment 1

[0035] The formula of Tippenem Methoxylate Granules is as follows:

[0036] Raw materials

Dosage g

Ratio w / w%

Tippenem

655

11.80

Microcrystalline cellulose

1000

18.02

sucrose

3000

54.05

Hydroxypropyl cellulose

45

0.81

talcum powder

49.3

0.89

Ethyl cellulose suspension

433

7.80

Hydroxypropylmethylcellulose

10.3

0.19

Aspartame

18.5

0.33

Ethyl acrylate-methyl methacrylate copolymer water dispersion

339

6.11

[0037] Refer to figure 1 , The preparation method of tippenem meximate granules includes the following steps:

[0038] Step S1: prepare a hydroxypropyl cellulose solution, mix the hydroxypropyl cellulose with pure water, and stir to prepare a solution with a mass percentage of 2 wt%; respectively prepare coating agent I and coating agent II into solutions for use;

[0039] Step S2: Pass the tipipenem ester and diluent through a 100-mesh sieve, weigh the formulated amount of tipipenem ester, microcrystalline cellulose and sucrose, and add them to the fluidized bed granulation...

Embodiment 2

[0047] The formula of Tippenem Methoxylate Granules is as follows:

[0048] Raw materials

Dosage g

Ratio w / w%

Tippenem

655

11.80

Microcrystalline cellulose

1000

18.02

sucrose

3000

54.05

Hydroxypropyl cellulose

45

0.81

talcum powder

49.3

0.89

Ethyl cellulose suspension

433

7.80

Hydroxypropylmethylcellulose

10.3

0.19

Aspartame

18.5

0.33

Ethyl acrylate-methyl methacrylate copolymer water dispersion

339

6.11

[0049] The preparation method of Tippenem Methoxylate granules includes the following steps:

[0050] Step S1: Prepare a hydroxypropyl cellulose solution, mix the hydroxypropyl cellulose with pure water, and stir to prepare a solution with a mass percentage of 2 wt%; respectively prepare coating agent I and coating agent II into solutions, see implementation Example 1, spare;

[0051] Step S2: Pass the tipipenem ester and diluent through a 120-mesh sieve, weigh the formula amount of tipipenem ester, microcrystalline cellulose and sucrose, add them to the fluidized bed granul...

Embodiment 3

[0057] The formula of Tippenem Methoxylate Granules is as follows:

[0058] Raw materials

Dosage g

Ratio w / w%

Tippenem

655

11.80

Microcrystalline cellulose

1000

18.02

sucrose

3000

54.05

Hydroxypropyl cellulose

45

0.81

talcum powder

49.3

0.89

Ethyl cellulose suspension

433

7.80

Hydroxypropylmethylcellulose

10.3

0.19

Aspartame

18.5

0.33

Ethyl acrylate-methyl methacrylate copolymer water dispersion

339

6.11

[0059] The preparation method of Tippenem Methoxylate granules includes the following steps:

[0060] Step S1: Prepare a hydroxypropyl cellulose solution, mix the hydroxypropyl cellulose with pure water, and stir to prepare a solution with a mass percentage of 2 wt%; respectively prepare coating agent I and coating agent II into solutions, see implementation Example 1, spare;

[0061] Step S2: Pass the tipipenem ester and diluent through a 200-mesh sieve, weigh the formula amount of tipipenem ester, microcrystalline cellulose and sucrose, add them to the fluidized bed granul...

Images