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WO2006015545A1 - Capsule de gelatine de moxifloxacin et procede pour sa preparation - Google Patents

Capsule de gelatine de moxifloxacin et procede pour sa preparation Download PDF

Info

Publication number
WO2006015545A1
WO2006015545A1 PCT/CN2005/001234 CN2005001234W WO2006015545A1 WO 2006015545 A1 WO2006015545 A1 WO 2006015545A1 CN 2005001234 W CN2005001234 W CN 2005001234W WO 2006015545 A1 WO2006015545 A1 WO 2006015545A1
Authority
WO
WIPO (PCT)
Prior art keywords
moxifloxacin
gelatin capsule
capsule
salt
hydrate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2005/001234
Other languages
English (en)
Chinese (zh)
Inventor
Bingqi Zhao
Xueqi Fu
Bangai Zhao
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen Tys R & D Co Ltd
Original Assignee
Shenzhen Tys R & D Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shenzhen Tys R & D Co Ltd filed Critical Shenzhen Tys R & D Co Ltd
Publication of WO2006015545A1 publication Critical patent/WO2006015545A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A61K9/4825—Proteins, e.g. gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Definitions

  • the present invention relates to a pharmaceutical preparation of moxifloxacin, and in particular, the present invention relates to a gelatin capsule of moxifloxacin or a salt thereof and/or a hydrate thereof, and a process for the preparation thereof.
  • Background technique
  • Moxifloxacin is a new generation of fluoroquinolone antibiotics. It is currently approved for the use of sensitive micro-organisms for upper and lower respiratory tract infections, such as acute exacerbation of chronic bronchitis, community acquired pneumonia, acute bacterial sinusitis and Treatment of uncomplicated skin and soft tissue infections.
  • the oral preparation of moxifloxacin only has moxifloxacin hydrochloride tablets
  • the Chinese patent "moxifloxacin pharmaceutical preparation" patent number 99813124. 5 discloses the oral pharmaceutical tablet, and the preparation method thereof, the drug and at least one An anhydrous binder and lactose are granulated with water, and the granules are then mixed with at least one disintegrant and at least one lubricant, and optionally tableted and coated.
  • Moxifloxacin capsules have not been reported so far.
  • the present inventors have found that the prior art preparation of moxifloxacin is filled in a gelatin capsule shell, and the dissolution property is lowered during storage, failing to meet the medicinal requirements. . ⁇
  • the gelatin capsule shell is a capsule which is commonly used for capsules.
  • the inventors filled the gelatin capsule shell with the preparation formula of moxifloxacin hydrochloride in the prior art, prepared a capsule, and measured the dissolution degree after performing the stability test for 60 days at 60 ° C for 10 days. It was found that the capsules were swollen and the capsules were not broken, and the contents could not be dissolved. Or even if some of the capsules were broken, they could not be completely dissolved after 45 minutes. The room temperature was observed and the dissolution began with the capsules for 15 days. The phenomenon that the placement time is extended and decreased.
  • the inventors further used a 3.5% or 5% HPMC solution to granulate the contents of the capsule containing moxifloxacin and then filled the capsules. After 10 days of stability test, the capsules did not dissolve or the dissolution decreased.
  • the above dissolution method is determined according to the first method of the Chinese Pharmacopoeia 2000 edition two appendix XC dissolution measurement method, the blue method lOOrpra, the eluate is 0. lmol / L hydrochloric acid, the content of the dissolved moxifloxacin determination method Using HPLC method).
  • the object of the present invention is to solve the above problems and to provide a moxifloxacin gelatin capsule which can improve the dissolution in storage and has stable dissolution properties and a preparation method thereof.
  • the present invention adopts the following technical solutions:
  • the present invention discloses a moxifloxacin gelatin capsule containing moxifloxacin or a salt thereof and/or a hydrate thereof, and the capsule content further comprising an additive selected from the following materials. At least one:
  • the additive added to the contents of the capsule may be a mixture of one or more of the above substances in order to maintain the effect of the present invention without physical form changes such as adhesion and agglomeration during the preparation process. And in the stability investigation does not affect the dissolution of the capsule and the stability of the main drug as a standard. In the present invention, the total amount of the additive added to the contents of the capsule should not exceed the normal dosage of the human body. None of the components added in the present invention were found to affect the chemical stability of the main drug.
  • the weight percentage of the additive in the capsule contents is from 0.1 to 20%.
  • the salt of moxifloxacin includes, for example, an acid addition salt such as a hydrochloride, and/or a hydrate thereof, and for example, moxifloxacin hydrochloride is particularly preferred in the present invention.
  • each capsule contains a unit dose required for clinical use.
  • each capsule of the present invention may contain 50 to 800 mg of the moxifloxacin or a salt thereof and/or a hydrate thereof, preferably 100 to 600 mg, particularly preferably 200 to 400 mg.
  • the capsule content of the capsule may further comprise a pharmaceutically acceptable amount of a pharmaceutically acceptable excipient, the medicinal excipient comprising one or more of a diluent, a disintegrant, a binder, a lubricant or a glidant.
  • a pharmaceutically acceptable excipient comprising one or more of a diluent, a disintegrant, a binder, a lubricant or a glidant.
  • diluents disintegrating agents such as microcrystalline cellulose, sodium carboxymethyl starch
  • the binder includes hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC); commonly used lubricants and help
  • the flow agent can be selected from magnesium stearate and micronized silica gel.
  • a pharmaceutically acceptable amount specifically refers to the amount of these excipients commonly used in the prior art. ⁇
  • the invention also discloses a preparation method of the above-mentioned moxifloxacin gelatin capsule, the method comprising the steps of: sufficiently mixing or granulating the moxifloxacin or a salt thereof and/or a hydrate thereof with the additive; Gelatin capsule shell. Further, the moxifloxacin or a salt thereof and/or a hydrate thereof is sufficiently mixed with the additive, and a pharmaceutically acceptable amount of a pharmaceutically acceptable excipient, or granulated, and filled into a gelatin capsule shell, the medicine
  • the excipients include one or more of a diluent, a disintegrant, a binder, a lubricant or a glidant.
  • the present invention also discloses another preparation method of the above-mentioned moxifloxacin gelatin capsule, which comprises the steps of: preparing the moxifloxacin or a salt thereof and/or a hydrate thereof with a coating liquid containing the additive; The granules are either powder coated, dried and filled into a gelatin capsule shell.
  • the granules are prepared or coated with a coating liquid containing the additive, After drying, it is filled into a gelatin capsule shell, and the pharmaceutical excipients include one or more of a diluent, a disintegrant, a binder, a lubricant or a glidant.
  • the additive can cause the insoluble or the dissolution of the capsule to occur during storage.
  • Obvious inhibition after adding the additive which accounts for 0.1 to 20% of the total weight of the capsule contents, the dissolution rate of the stalk capsule is in the stability test of 10 ⁇ 60 ° C, and the insoluble solution is not added when the additive is added. Or less than 50% increased to more than 80%, and after accelerated stability investigation (40 ° C, relative humidity 75% acceleration stability for three months), the dissolution properties are still stable, the dissolution rate is above 80%.
  • moxifloxacin hydrochloride used in the present invention is as follows:
  • the gelatin capsule used in the present invention is produced by China Suzhou Capsule Co., Ltd., the gelatin capsule meets the medicinal standard, and other accessories and additives are in compliance with medicinal or food. Additive standard.
  • Example 4 The above 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, which is translated by croscarmellose soldium. Come, see the second page of the original patent specification, and in fact the translation is wrong, correctly translated as cross-linked sodium carboxymethyl cellulose (disintegrant).
  • the capsules and tablets prepared above were sealed in a composite aluminum foil bag, and the dissolution was measured after 30 days of stability at 40 ° C (according to the Chinese Pharmacopoeia 2000 edition two appendix XC dissolution method)
  • the first method is determined by the blue method, the rotation speed is lOO rpm, the eluate is 0.1 mol/L hydrochloric acid, the sampling time is 45 minutes, and the content of the dissolved moxifloxacin is determined by HPLC method.
  • composition and preparation Take moxifloxacin hydrochloride 218. 4rag, directly filled gelatin capsules.
  • the dissolution test was carried out by the method of measuring the dissolution as described in Test 1.
  • Composition As shown in Table 3 to Table 8, respectively.
  • Example 28 29 30 32 Components Moxifloxacin hydrochloride 218.4 218.4 218.4 218.4 218.4 218.4 Microcrystalline cellulose 48.65 47.3 29.0 16.0 16.0 Carboxymethyl starch sodium 56.0 56.0 56.0 56.0 24.0 Magnesium stearate 6.6 6.6 6.6 6.6 Tea polyphenol 0.35 1.7 20 33 65 Total 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 330.0 Dissolution (0 days) (%) 99 100 97 98 99 Dissolution (40 ⁇ , relative humidity 75% 85 99 99 99 96 101 Accelerated stability for three months) (%) Table 6 (each capsule component, unit Is mg)
  • Composition as shown in Table 9 to Table 10 respectively
  • Vitamin B1 0.05 1.0 0.35 50
  • Vitamin B2 0.05 0.5 0.35 20

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Botany (AREA)
  • Zoology (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention divulgue un type de capsule de of moxifloxacin. Le contenu de la capsule comprend du moxifloxacin ou son sel et/ou ses hydrates et additifs. Lesdits additifs sélectionnés à partir d’au moins des matériaux suivants : sulfite de sodium; bisulfite de sodium; anthocyanidin oligomérique; glutathion-L; polyphénols de sesame; polyphénols de thé; tocophérol; acide antiscorbic; acid araboascorbic; Vitamine B1; Vitamine B2; carotène β; soja isoflavone; cystéine-L; acide pyrophosphoric; polyphosphate et leur sel pharmaceutique. Des additifs peuvent être ajoutés au contenu de la capsule par procédé conventionnel. Des additifs ont un effet inhibiteur évident sur le décroissement de la dissolution durant le processus de stockage. Ceci améliore grandement l’efficacité de la dissolution de la capsule
PCT/CN2005/001234 2004-08-11 2005-08-11 Capsule de gelatine de moxifloxacin et procede pour sa preparation Ceased WO2006015545A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200410058049 2004-08-11
CN200410058049.9 2004-08-11

Publications (1)

Publication Number Publication Date
WO2006015545A1 true WO2006015545A1 (fr) 2006-02-16

Family

ID=35839139

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2005/001234 Ceased WO2006015545A1 (fr) 2004-08-11 2005-08-11 Capsule de gelatine de moxifloxacin et procede pour sa preparation

Country Status (1)

Country Link
WO (1) WO2006015545A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112274492A (zh) * 2020-10-30 2021-01-29 重庆华邦制药有限公司 度他雄胺软胶囊及其组合物和制备方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN87100810A (zh) * 1986-01-21 1987-10-14 拜尔公司 环丙氟氧新的药物配方
US5478829A (en) * 1991-09-27 1995-12-26 Rhone-Dpc Europe Solution of sparfloxacin, its preparation and salt of which it is composed
CN1320035A (zh) * 1998-09-30 2001-10-31 阿尔康实验室公司 治疗眼、耳和鼻的抗生素组合物
CN1325306A (zh) * 1998-11-10 2001-12-05 拜尔公司 莫西沙星药物制剂
CN1368891A (zh) * 1999-08-06 2002-09-11 拜尔公司 莫西沙星/氯化钠制剂
CN1480218A (zh) * 2002-06-21 2004-03-10 缓慢释放生物活性物质的药物制剂及其制备方法与应用
WO2005020998A1 (fr) * 2003-09-03 2005-03-10 Ranbaxy Laboratories Limited Compositions pharmaceutiques a base de moxifloxacine et leurs procedes de preparation

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN87100810A (zh) * 1986-01-21 1987-10-14 拜尔公司 环丙氟氧新的药物配方
US5478829A (en) * 1991-09-27 1995-12-26 Rhone-Dpc Europe Solution of sparfloxacin, its preparation and salt of which it is composed
CN1320035A (zh) * 1998-09-30 2001-10-31 阿尔康实验室公司 治疗眼、耳和鼻的抗生素组合物
CN1325306A (zh) * 1998-11-10 2001-12-05 拜尔公司 莫西沙星药物制剂
CN1368891A (zh) * 1999-08-06 2002-09-11 拜尔公司 莫西沙星/氯化钠制剂
CN1480218A (zh) * 2002-06-21 2004-03-10 缓慢释放生物活性物质的药物制剂及其制备方法与应用
WO2005020998A1 (fr) * 2003-09-03 2005-03-10 Ranbaxy Laboratories Limited Compositions pharmaceutiques a base de moxifloxacine et leurs procedes de preparation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112274492A (zh) * 2020-10-30 2021-01-29 重庆华邦制药有限公司 度他雄胺软胶囊及其组合物和制备方法

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