WO2007033515A1

WO2007033515A1 - Oral formulation containing moxifloxacin and its preparation method

Info

Publication number: WO2007033515A1
Application number: PCT/CN2005/001504
Authority: WO
Inventors: Xue Qi Fu; Bang Ai Zhao; Bing Qi Zhang
Original assignee: Shenzhen Tys R & D Co., Ltd.
Priority date: 2005-09-21
Filing date: 2005-09-21
Publication date: 2007-03-29

Abstract

An oral tablet formulation of moxifloxacin or its salts and/or hydrates, comprises at least one film-forming material used for coating the intermediate particles. Said film-forming material may be one or more of hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, sodium carboxymethycellulose, polyacrylic resins, polyethylene glycol, polyvinylpyrrolidone vinylacetate copolymer, PVA-PEG graft copolymer, carbopol, gelatin, poloxamer, polyvinylpyrrolidone. Preparation of said formulation comprises: mixing or granulating moxifloxacin blended with excipients, coating the intermediate granular with the film- forming material, then compressing the mixture. The invented tablet formulation has a prolonged shelf life and rapid dissolution.

Description

Moxifloxacin oral pharmaceutical preparation and preparation method thereof

Technical field

The present invention relates to a pharmaceutical preparation and a preparation method thereof, and in particular, the present invention relates to a moxifloxacin

Stable oral pharmaceutical preparation of (raoxifloxacin) or a salt thereof and/or its hydrate and a method for preparing the same. Background technique

Moxifloxacin is a new generation of fluoroquinolone antibiotics. Currently, moxifloxacin hydrochloride has been approved for upper and lower respiratory tract infections caused by sensitive microorganisms, such as acute exacerbation of chronic bronchitis, community acquired pneumonia, acute bacterial sinusitis and Treatment of uncomplicated skin and soft tissue infections.

Moxifloxacin hydrochloride tablets were first registered in Mexico in February 1999 and first in Germany in September 1999. Infusions were first marketed in the United States and Germany in December 2001. Currently, the products are already in Germany, Spain, Italy, Sweden. Listed in Switzerland, the United States, Canada, Australia, Argentina, Brazil, South Korea, Malaysia and other countries.

Chinese patent "Moxifloxacin Pharmaceutical Preparation", Patent No. 99813124. 5 The preparation process of moxifloxacin tablets is to granulate the drug with at least one anhydrous binder and lactose, and then to granulate the particles with at least one The disintegrant is mixed with at least one lubricant and optionally tableted and coated. This patent feature improves the hardness or breaking load of the prior patent (EP-A-0350733) tablet by using 2. 5 to 25% of the lactose in the formulation, while obtaining excellent release properties.

The Chinese patent "Moxifloxacin Pharmaceutical Preparation", at least one anhydrous binder mentioned in Patent No. 99813124. 5, the original patent applicant cites microcrystalline cellulose, fibrous cellulose, calcium phosphate mannose in the specification. The sugar alcohol, and preferably microcrystalline cellulose, does not have film forming properties.

The Chinese patent "Moxifloxacin Pharmaceutical Preparation", Patent No. 99813124. 5 mentions that the pharmaceutical preparation of the invention is preferably in the form of a tablet, which may optionally be coated, for the coating, Coating agents commonly used in the pharmaceutical field, such as various hydroxypropyl methylcellulose (HPMC) and/or polyethylene glycol, may also be used, and the coating may also contain conventional pigments such as titanium dioxide or iron oxide red. . The coating material specifically mentioned in Examples 1, 4, 5, and 6 was HPMC. However, in this patent document, the coatings referred to refer to the coating of the tablet of the tablet, and it is not mentioned that the film-forming material is used to prepare the intermediate particles or to coat the particles.

The patent applicant has previously designed two test formulations and compared it with the Chinese patent "Moxifloxacin Pharmaceuticals".

1 Confirmation The formula of the "agent" (patent number 99813124. 5) was compared. The three parties all refer to the process of the comparative patent (patent number 99813124. 5), and the granules are compressed by water. The specific formula and the results of the investigation are shown in Table 1, Table 2.

Table 1 Moxifloxacin hydrochloride tablets formula

Remarks: *: The comparative patent formula is Chinese patent 99813124. 5 Example 4, containing lactose. Self-test formula

1-containing lactose; self-tested formula 2 does not contain lactose.

**: The comparative patent formulation is the uncoated core formulation of Example 4 in the Chinese patent (Patent No. 99813124. 5, Publication No. CN1325306A), but in the publication, ** is sodium carboxymethylcellulose, Translated from croscarmellose soldium, see the second page of the original patent specification, and in fact the translation is incorrect, correctly translated as croscarmellose sodium (disintegrant).

Table 2. Comparison of the quality of the three formula cores

Remarks: The hardness is measured by Mansanto hardness tester. The friability, disintegration degree and dissolution rate are determined according to the Chinese Pharmacopoeia 2000 version. The dissolution method is determined according to the first method in the Chinese Pharmacopoeia 2000 edition two appendix XC. The dissolution medium is 0.1 M hydrochloric acid solution, the rotation speed is 100 rpm, and the measurement is performed. The dissolution value was 45 minutes.

As can be seen from Table 2, the hardness, friability, disintegration, and dissolution of the three formulations were comparable. However, in the tablet pressing process prepared by the above three formulations, it was found that the appearance or edge of the tablet often showed a red color, suggesting that new impurities were generated.

The stability study of moxifloxacin hydrochloride was found to be in contact with metallic iron, especially under moist heat conditions, causing discoloration of moxifloxacin hydrochloride (from yellow to red). During the preparation process, moxifloxacin hydrochloride can be discolored after contact with iron container or stainless steel punch, die or friction. Therefore, the granulation and drying of the preparation should avoid the use of iron-containing containers, usually containing moxifloxa hydrochloride during tableting. The contact of the particles of the star with the punch and the die is inevitable.

At present, there is no literature on the pharmacological and toxicological effects of moxifloxacin hydrochloride raw materials or red impurities produced during tableting, and it is not known that it is harmless to the human body. Summary of the invention

The object of the present invention is to solve the problem that moxifloxacin produces red impurities during the preparation process, especially during tableting, and provides a stable oral pharmaceutical preparation of moxifloxacin, especially a tablet, and a preparation method of the same The prepared tablets have good hardness and dissolution properties.

To achieve the above object, the present invention adopts the following technical solutions:

The present invention discloses an oral pharmaceutical preparation of moxifloxacin containing moxifloxacin or a salt thereof and/or a hydrate thereof, the pharmaceutical preparation further comprising at least one intermediate granule for preparing a preparation or powder or granule package a film forming material of the garment, the film forming material comprising:

Hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, polyacrylic resins, polyethylene glycol, Polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol-'polyethylene glycol graft copolymer, Carbopol, gelatin, poloxamer, polyvinylpyrrolidone. +

Among them, the polyacrylic resin is also often referred to as a poly(meth)acrylic resin.

The moxifloxacin oral pharmaceutical preparation is preferably present in the form of a tablet, or may be an oral preparation such as a granule dosage form. When a tablet is preferred, the tablet of the tablet may optionally be coated. For the coating of the tablet, a coating formulation commonly used in the pharmaceutical field may be used, such as various hydroxypropyl methylcellulose. Based on (HPMC) and/or polyethylene glycol, the coating may also contain conventional pigments such as titanium dioxide or iron oxide red.

0%。 0%. 0%. 0%. 5〜10. 0%。 0%.

The moxifloxacin or a salt thereof and/or a hydrate thereof thereof means moxifloxacin hydrochloride.

The pharmaceutical formulation also contains a pharmaceutically acceptable amount of a pharmaceutically acceptable excipient.

The excipients include starch, dextrin, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, croscarmellose sodium, micronized silica gel, magnesium stearate, lactose. Among them, lactose is not essential in the present invention.

In a preferred set of the invention, the pharmaceutical preparation contains '

a weight percentage of 30 to 60% of moxifloxacin hydrochloride;

0% hydroxypropyl methylcellulose;

a percentage by weight of 31 to 50% of microcrystalline cellulose;

5 to 20% by weight of pregelatinized starch;

1% to 10% by weight of sodium carboxymethyl starch;

5% by weight of croscarmellose sodium;

5%的镁脂镁。 The weight percentage is 0. 5~2. 5% magnesium stearate.

In another set of embodiments of the invention, the pharmaceutical preparation contains

50% to 76% by weight of moxifloxacin hydrochloride;

% by weight of the film forming material hydroxypropyl methylcellulose;

The weight percentage is 0. 2~10. 0% of the film forming material polyethylene glycol;

5 to 30% by weight of microcrystalline cellulose;

5% by weight of lactose;

Between 10% by weight of croscarmellose sodium;

5%的镁脂镁。 The weight percentage is 0. 5~2. 5% magnesium stearate.

5〜10。 The film-forming material is 0. 5~10. /. An aqueous solution or a water-dispersed solution or a dilute ethanol solution, which is prepared as a binder by mixing with moxifloxacin or a salt thereof and/or a hydrate thereof and a pharmaceutically acceptable excipient; or

a part of the film-forming material is mixed with moxifloxacin or a salt thereof and/or a hydrate thereof and a pharmaceutically acceptable excipient, and the remaining part of the film-forming material is formulated into a weight percentage of 0.5 to 10% of an aqueous solution or a water-dispersed solution or dilute ethanol. a solution, prepared as a binder and mixed with the above mixture; or

After the film-forming material is mixed with moxifloxacin or a salt thereof and/or a hydrate thereof and a pharmaceutically acceptable excipient, the granule is prepared by using a soft material made of water or dilute ethanol; or The film-forming material is formulated into a 0.5% by weight aqueous solution or a water-dispersed solution or a dilute ethanol solution, a powder of moxifloxacin or a salt thereof and/or a hydrate thereof and a pharmaceutically acceptable excipient or The granules are coated.

The method further comprises the step of drying the finished granules or coated granules, adding magnesium stearate, mixing and then tableting to form a tablet.

0%。 0%。 0%. 0%. '

0%。 0%。 0%. 0%. 0%.

The pharmaceutically acceptable excipients include starch, dextrin, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, croscarmellose sodium, micronized silica gel, magnesium stearate, lactose. Among them, lactose is not essential in the present invention.

Since the above scheme is used, the beneficial effects of the present invention are as follows:

Since the film-forming materials listed in the present invention are used for preparing intermediate particles, or coating powders or granules, the oral pharmaceutical preparations of moxifloxacin of the present invention, particularly tablets, can be granulated and tableted. It maintains stable properties, does not cause discoloration after contact with iron container or stainless steel punch, die or friction, bright, good hardness, and rapid drug dissolution; and can ensure quality after long-term storage, such as tablet core placed at room temperature The quality remained unchanged for two years, the hardness did not change significantly, the color remained yellow, and the dissolution rate remained above 90%.

detailed description

The method for obtaining a stable moxifloxacin or a salt thereof and/or a hydrate tablet thereof according to the present invention is granulated by a film-forming material granule or coating granulation. The film-forming material used may be hydroxypropylmethylcellulose (HPMC), hydroxyethylmethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, poly (Meth) Acrylic Resins (stomach-soluble or gastric-dispersed), polyethylene glycol, polyvinylpyrrolidone-vinyl acetate copolymer (eg Kollidon® VA64 or Plasdone® S-630), polyvinyl alcohol- A mixture of one or more of a polyethylene glycol graft copolymer (such as Kollicoat® IR), Carbopol, gelatin, and poloxamer. 0%。 0%. 2%. 0%.

The film-forming material is used as a binder, and the concentration of the film is 0. 5~10. 0%; The remaining part of the film-forming material is mixed with the main drug and other auxiliary materials, and the ratio of the film-forming material used for formulating the solution to the total amount of the film-forming material used is not particularly limited, and only needs to satisfy the solution used as the binder and When the remaining part of the film-forming material, main drug and other auxiliary materials are mixed to prepare granules, the mixture is kept at the necessary humidity; all the film-forming materials and main drugs and other auxiliary materials can also be used. Mixing, making suitable soft material post-granulation with water or dilute ethanol; and coating the powder or granules of moxifloxacin with a film forming material solution. The dilute ethanol is usually 30%~50% ethanol.

Granulation and drying can be carried out by conventional methods. Such as high-speed mixing granulation, or bubbling granulation drying.

The discoloration of the edge of the tablet caused by the rubbing of the drug with the metal punch and the die during the tableting process is solved by using the film forming material and the above granulation method.

The pharmaceutical preparation of the present invention may further contain an appropriate amount of excipients, which may be selected from the following excipients: starch, dextrin, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crosslinked carboxymethyl Cellulose sodium, micronized silica gel, magnesium stearate, lactose. It can also be free of lactose.

The invention is further described in detail below by way of specific examples. Example 1

Moxifloxacin hydrochloride 218. 4 mg

Microcrystalline cellulose 124. 6 mg

Pregelatinized starch 37. Omg

Sodium Carboxymethyl Starch 7. 0 mg

Cross-linked carboxymethylcellulose sodium 7. Omg

Magnesium stearate 4. 7mg

HPMC (90SH 100) 1. 3mg

Total weight 400. 0 mg

The raw materials and auxiliary materials (except magnesium stearate and HPMC) of the above components are thoroughly mixed uniformly, and granules are prepared by using 1.0% of HPMC aqueous solution, dried, and then added with magnesium stearate to be mixed and tableted. The punch and die used for tableting are made of stainless steel.

The prepared tablet core may be conventionally coated or may be directly packaged in a light-proof sealed package without coating.

The tablet quality was examined immediately after preparation and two years later, and the results are shown in Table 6. Example 2

Component: Moxifloxacin Hydrochloride 218. 4 mg

Microcrystalline cellulose 124. 6 mg

Pregelatinized starch 34. 3mg Carboxymethyl starch sodium 7. 0 nig

Cross-linked carboxymethylcellulose sodium 7. 0mg

Magnesium stearate 4. 7mg

HPMC (90SH 100) 4. Omg

Total weight 400. 0 mg

Take the raw materials and auxiliary materials (except magnesium stearate and HPMC) in the above components and mix them thoroughly. Make granules with 3.0% HPMC dilute ethanol solution (diluted ethanol is 50% ethanol), add magnesium stearate after drying. Mix, press, and get. The punch and die used for tableting are made of stainless steel. '

The prepared tablet core may be coated by a conventional method or may be directly packaged in a light-proof sealed package without coating.

The tablet quality was examined after the preparation was completed and after two years, and the results are shown in Table 6. Example 3

Moxifloxacin hydrochloride 218. 4 mg

Microcrystalline cellulose 124. 6 mg

Pregelatinized starch 31. 5mg

Sodium Carboxymethyl Starch 7. 0 mg

Cross-linked carboxymethylcellulose sodium 7. Omg

Magnesium stearate 4. 3mg

HPMC (90SH 100 ) 7. 2mg

^! , 400. 0 mg

The raw materials and auxiliary materials (except magnesium stearate and HPMC) of the above components are thoroughly mixed uniformly, and granules are prepared by using 4.5% of HPMC aqueous solution, dried, and then added with magnesium stearate to be mixed and tableted. The punch and die used for tableting are made of stainless steel.

The prepared tablet core may be coated by a conventional method or may be directly coated with a light-proof sealed package without coating.

The tablet quality was examined immediately after preparation and two years later, and the results are shown in Table 6. Example 4

Component: Moxifloxacin hydrochloride 436. 8 mg

Microcrystalline cellulose 230. 0 mg Pregelatinized starch 60. 2mg

Carboxymethyl starch sodium 13. 0 mg

Cross-linked sodium carboxymethyl cellulose 9. Orag

Barium stearate 6. Omg

HPMC (90SH 100 ) 4. 5mg

Kappo (934 P) 0. 5mg

Total weight 760. 0 mg

0%溶液。 The above components of the composition of the raw materials, in addition to the above, the amount of the above-mentioned HPMC and Kappabo in the diluted ethanol (50%) was 3.0% by weight The solution is mixed with the above mixture to prepare granules, dried, and then added with magnesium stearate to be mixed and tableted. The punch and die used for tableting are made of stainless steel.

The tablet quality was examined immediately after preparation and two years later, and the results are shown in Table 6. Example 5

Moxifloxacin hydrochloride 218. 4 rag

Microcrystalline cellulose 124. 6 mg

Pregelatinized starch 32. 3mg

Sodium Carboxymethyl Starch 7. 0 mg

Cross-linked carboxymethylcellulose sodium 7. Omg

Magnesium stearate 4. 7mg

Polyethylene glycol (PEG) 6000 5. Omg

HPMC (90SH 100 ) 1. Omg

400. 0 mg

The above ingredients were mixed with the raw materials (except magnesium stearate, PEG and HPMC), and PEG and HPMC were mixed to prepare an aqueous solution having a concentration of 5.0%. The aqueous solution was used to prepare granules, and after drying, stearic acid was added. Mix the magnesium, compress it, and get it. The punch and die used for tableting are made of stainless steel.

The tablet quality was examined after the preparation was completed and after two years, and the results are shown in Table 6. Example 6

Moxifloxacin hydrochloride

Microcrystalline cellulose 129.6 rag

Pregelatinized starch 34. Omg

Carboxymethyl starch sodium 7.0 mg

Cross-linked carboxymethylcellulose sodium 7. Omg

Magnesium stearate 4. Omg

Total 400.0 mg

The raw materials and auxiliary materials (except magnesium stearate) of the above components are thoroughly mixed and uniformly mixed, and the powder coating is carried out with the following solution; or the raw materials and the auxiliary materials are thoroughly mixed and dry granulated, and then the following solution is used for granule coating. After the granule coating, the weight gain of the original and auxiliary materials was 8%, that is, the granule-coated preparation contained 0.8% of polyethylene glycol 4000 and 7.2% of HPMC (90SH 100). Then add magnesium stearate to mix and compress, then obtain. The punch and die used for tableting are made of stainless steel.

HPMC (90SH 100) 7.2g

Polyethylene glycol 4000 0.8g

ΤΚ 92.0g

100.0g

The tablet quality was examined immediately after preparation and two years later, and the results are shown in Table 6. Example 7-10

Mix the components of each of the formulations in Table 3 below (except magnesium stearate), then add a small amount of water or dilute ethanol (30% ethanol) to make a suitable soft material, then granulate, dry and then add Mix magnesium stearate and compress. Similarly, the punch and die used for tableting are made of stainless steel.

Table 3. (Unit of weight: mg)

Original and auxiliary materials Example 7 Example 8 Example 9 Example 10 Moxifloxacin hydrochloride 218.4 218.4 218.4 218.4 Microcrystalline cellulose 116.6 116.6 116.6 116.6 Pregelatinized starch ' 32.0 32.0 32.0 32.0 Sodium Carboxymethyl Starch 7.0 7.0 7.0. 7.0 Croscone Sodium Cellulose 7.0 7.0 7.0 7.0

Methyl cellulose 5

Hydroxyethyl cellulose 10

Hydroxypropyl cellulose 15

Methionine 10

Gelatin 5

Carboxymethylcellulose sodium 15

Magnesium stearate 4.0 4.0 4.0 4.0 Soft solvent Solvent Water 30% Ethanol Water Total 400 400 400 400 The tablet quality was examined immediately after preparation and two years later. The results are shown in Table 6. Example 11 - 12

The non-film-forming material components other than magnesium stearate in Table 4 below were thoroughly mixed uniformly, and the powder coating was carried out with the coating liquid component containing the coating liquid component in Table 4 and the amount, and then the hard fat was added. The magnesium acid mixed hook, tablet, and the punch and die used for tableting are made of stainless steel.

Table 4 (weight in mg)

Sample Π original, auxiliary material Example 11 Example 12

Non-moxafloxacin hydrochloride 218.4 218.4

Microcrystalline cellulose 119.6 128.6

Membrane pregelatinized starch 34.0 30.0

Sodium Carboxymethyl Starch 7.0 7.0

Cross-linked carboxymethylcellulose sodium 7.0 7.0

Magnesium stearate 4.0 4.0

Coating Utech RD100 20.0

Liquid group Kollicoat IR 20.0 Component PEG 6000 10 5

, 1⁄23⁄4 蜃里 420 420

Among them, Utech RD100 is a poly(meth)acrylic resin, and Kollicoat IR is a polyvinyl alcohol-polyethylene glycol graft copolymer.

The tablet quality was examined immediately after preparation and two years later, and the results are shown in Table 6. Example 13

Original and auxiliary dosage (mg) Moxifloxacin hydrochloride 218. 4

Microcrystalline cellulose 98. 6

Pregelatinized starch 10. 0

Carboxymethyl starch sodium 7. 0

Croscarmellose sodium 7. 0

Polyvinylpyrrolidone-vinyl acetate copolymer (S-630) 10. 0

Polosham F- 68 30. 0

PEG 6000 35. 0

Magnesium stearate 4. 0

Total quantity (mg) 420

Take the raw materials and auxiliary materials (except magnesium stearate) in the above components and mix well. Add appropriate amount of water to make granules. After drying, add magnesium stearate and mix the hooks. Press the metal punch and die to obtain the plain tablets. Coated, or uncoated, directly sealed in a light-proof package.

The tablet quality was examined immediately after preparation and two years later, and the results are shown in Table 6. Example 14 19

Mix the components of each of the formulations of Table 5 (except magnesium stearate) in the following Table 5, and then add appropriate amount of water to make suitable soft materials and then prepare the granules. After drying, add magnesium stearate and mix. Metal punch and die compression.

Table 5. (Unit of weight: mg)

Raw materials, implementation, implementation, implementation, implementation, implementation

Example 14 Example 15 Example 16 Case 17 Case 18 Case 19 Moxifloxacin hydrochloride 54.6 54.6 54.6 218.4 436.8 436.8 Microcrystalline cellulose 17.0 7.1 12.8 88.0 136.0 136.0

Lactose 8.5 3.6 12.8 60.0 68.0 68.0 croscarmellose sodium 2.0 2.7 3.4 8.0 16.0 32.0

HPMC C90SH 100) 2.5 4.0 5.0 11.0 44.0 30.0 Polyethylene glycol 4000 0.4 1.0 3.0 9.0 15.0 8.0 Magnesium stearate 0.6 0.4 0.5 2.4 4.8 6.0

M doctor

Ή, 里 85.6 73.4 92.1 396.8 720.6 716.8 The quality of the tablets was examined immediately after the completion of the preparation and two years later. The results are shown in Table 6. Example 20

Component: Moxifloxacin Hydrochloride 218. 4 mg

Microcrystalline cellulose 150. 6 mg

Carboxymethyl starch 14. 0 mg

Magnesium stearate 4. 7rag

Polyvinylpyrrolidone 12. 3mg

All the raw materials and auxiliary materials except the magnesium stearate are uniformly mixed, and the granules are prepared by using water. After drying, the magnesium stearate is added and mixed, and the tablet is obtained. The punch and die used for tableting are made of stainless steel.

The prepared tablets can be directly packaged in a light-tight seal.

The tablet quality was examined immediately after preparation and two years later, and the results are shown in Table 6.

Table 6. Results of tablet quality investigation of each example

Hardness (kg) Color Dissolution (%) Quality Index

0月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月月 13 13 13 Yellow yellow 99.2 99.5 Example 2 14 14 Yellow yellow 98.1 97.8 Example 3 15 14 Yellow Yellow 97.8 97.5 Example 4 14 14 Yellow Yellow 99.0 99.1 Example 5 12 12 Yellow Yellow 100.5 99.3 Example 6 12 12 Yellow Yellow 99.0 99.3 Example Ί 13 13 Yellow Yellow 100.5 98.7 Example 8 14 14 Yellow yellow 98.6 99.9 Example 9 14 14 Yellow yellow 98.1 98.5 Example 10 14 14 Yellow yellow 98.2 97.1 Example 11 13 13 Yellow yellow 99.2 101.5 Example 12 14 15 Yellow yellow 98.3 96.1 Example 13 13 13 Yellow yellow 95.5 97.0 Implementation Example 14 14 14 Yellow Yellow 99.1 102.5 Example 15 14 14 Yellow Yellow 98.2 98.1 Example 16 13 13 Yellow Yellow 99.2 99.5 Example 17 14 15 Yellow Yellow 97.3 99.1 Example 18 13 13 Yellow Yellow 99.5 101.0 Example 19 13 13 Yellow Yellow 98.1 101.3 Example 20 14 14 ^Color Yellow 99.5 100.8 Note: 'Hardness is determined using a Mansanto hardness tester;

The dissolution rate was determined according to the first method of the Chinese Pharmacopoeia 2000 edition two appendix XC dissolution method, and the dissolution medium 1M hydrochloric acid solution was rotated at 100 rpm to determine the dissolution value for 45 minutes.

Claims

1. An oral pharmaceutical preparation of moxifloxacin, comprising moxifloxacin or a salt thereof and/or a hydrate thereof, characterized in that: the pharmaceutical preparation further comprises at least one film-forming material, and the film-forming material is used in a preparation site. The intermediate particles of the oral pharmaceutical preparation of moxifloxacin or powder or granule coating, the film-forming material comprises - hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, methylcellulose, hydroxypropyl Cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyacrylic resin, polyethylene glycol, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol-polyethylene glycol graft copolymer, card Carbopol, gelatin, poloxamer, polyvinylpyrrolidone.

The oral pharmaceutical preparation of moxifloxacin according to claim 1, wherein the oral pharmaceutical preparation of moxifloxacin is a tablet. ,

0%。 0%。 0%. 0%. 0%.

5〜10, 0%。 The weight percentage of the pharmaceutical preparation is 0. 5~10, 0%.

The oral pharmaceutical preparation of moxifloxacin according to any one of claims 1 to 4, wherein the moxifloxacin or a salt thereof and/or a hydrate thereof thereof means moxifloxacin hydrochloride.

The oral pharmaceutical preparation of moxifloxacin according to any one of claims 1 to 4, wherein the pharmaceutical preparation further comprises a pharmaceutically acceptable amount of a pharmaceutically acceptable excipient.

The oral pharmaceutical preparation of moxifloxacin according to claim 6, wherein the excipient comprises starch, dextrin, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linking. Sodium carboxymethylcellulose, silica gel, magnesium stearate, lactose.

8. The oral pharmaceutical preparation of moxifloxacin according to claim 7, wherein: the pharmaceutical preparation contains

a weight percentage of 30 to 60% of moxifloxacin hydrochloride;

% by weight of 0. 2~2. 0% of the film-forming material hydroxypropyl methylcellulose;

a percentage by weight of 31 to 50% of microcrystalline cellulose;

a pregelatinized starch having a weight percentage of 5 to 20%; a percentage by weight of 1 to 10% sodium carboxymethyl starch;

5% by weight of croscarmellose sodium;

5%的镁脂镁。 The weight percentage is 0. 5~2. 5% magnesium stearate.

9. The oral pharmaceutical preparation of moxifloxacin according to claim 7, wherein: the pharmaceutical preparation contains

50% to 76% by weight of moxifloxacin hydrochloride;

% by weight of the film forming material hydroxypropyl methylcellulose;

5 to 30% by weight of microcrystalline cellulose;

5% by weight of lactose;

Between 10% by weight of croscarmellose sodium;

5%的镁脂镁。 The weight percentage is 0. 5~2. 5% magnesium stearate.

10, according to a method for preparing moxifloxacin oral pharmaceutical formulation as claimed in claim, the method comprising the steps _of: forming said material formulated -5 to 0.5 weight percent of a 10% aqueous solution or dispersion or solution a dilute ethanol solution, prepared as a binder by mixing with moxifloxacin or a salt thereof and/or a hydrate thereof and a pharmaceutically acceptable excipient; or

5〜10%的水溶液或水分散溶液或稀稀。 The part of the film-forming material is mixed with moxifloxacin or its salt and / or its hydrate and pharmaceutically acceptable excipients, the remaining part of the film-forming material is 0. 5~10% aqueous solution or water dispersion solution or thin An ethanol solution, which is mixed as a binder with the above mixture to prepare granules; or

The film-forming material is mixed with moxifloxacin or a salt thereof and/or a hydrate thereof and a pharmaceutically acceptable excipient, and then prepared by using water or dilute ethanol to prepare a granule; or

The film-forming material is formulated into a 0.5% by weight aqueous solution or a water-dispersed solution or a dilute ethanol solution, a powder of moxifloxacin or a salt thereof and/or a hydrate thereof and a pharmaceutically acceptable excipient or The granules are coated. ·

The method for preparing a moxifloxacin oral pharmaceutical preparation according to claim 10, wherein the method further comprises: adding the prepared granules or the coated granules to dryness, and then adding magnesium stearate, After mixing, the tablets were compressed.

2〜20. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 %.

0%。 0%。 0%. 0%. 0%. 0%. 0%.

The method for producing a moxifloxacin oral pharmaceutical preparation according to claim 13, wherein the moxifloxacin or a salt thereof and/or a hydrate thereof means moxifloxacin hydrochloride.

The method for preparing a moxifloxacin oral pharmaceutical preparation according to claim 14, wherein the pharmaceutically acceptable excipient comprises starch, dextrin, pregelatinized starch, microcrystalline cellulose, and carboxymethyl Sodium starch, croscarmellose sodium, micronized silica gel, magnesium stearate, lactose.