Classifications

• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2833—Organic macromolecular compounds
  • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
  • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• • 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
  • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2009—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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
  • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

• moxifloxacin is l-cyclopropyl-7- ([S, S]-2,8-diazabicyclo [4.3. 0] non-8-yl)-6-fluoro-l, 4-dihydro-8-methoxy-4-oxo-3-quinolonecarboxylic acid. It is an antiinfective agent and is known from U.S. Patent No. 4,990,517.
• Moxifloxacin can be used for the treatment of various infections, like acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and community acquired pneumonia.
• U.S. Patent No. 4,990,517 discloses a pharmaceutical preparation that includes the active compound, with microcrystalline cellulose, maize starch, poly- (l-vinyl)-2- pyrrolidone (insoluble), finely divided silica and magnesium stearate.
• U.S. Patent No. 5,286,754 discloses pharmaceutical formulations of ciprofloxacin that include binder based on cellulose, disintegrant based on starch, and a disintegrant based on cellulose derivatives and/or cross-linked polyvinylpyrrolidones.
• Patent No. 6,610,327 discloses pharmaceutical preparations for oral administration that includes moxifloxacin or a salt or solvate/hydrate thereof, at least one dry binder, at least one disintegrant and at least one lubricant, characterized in that the preparation contains 2.5 % to 25% of lactose.
• the inventors have surprisingly found that bioequivalent formulations to commercially available Avelox tablet formulations can be obtained by mtragranular and extragranular distribution of substantially water insoluble pharmaceutical excipients. Summary of the Invention In one general aspect there is provided a pharmaceutical composition that includes moxifloxacin and at least one mtragranular and extragranular substantially water insoluble excipient.
• Embodiments of the composition may include one or more of the following features.
• the composition may further include other pharmaceutically accepted excipients.
• the other excipients may include one or more of binders, disintegerants, fillers, lubricants/glidants, and colorants.
• the substantially insoluble excipients may include one or more of microcrystalline cellulose, pregelatinized starch, dicalcium phosphate dibasic, corn starch, and the like.
• the binders may be one or more of polyvinyl pyrrolidone, hydroxypropyl cellulose and gums.
• the fillers may be one or more of cellulose derivatives, starch derivatives, sugars, sugar alcohols, and the like.
• the disintegrant may be one or more of pregelatinized starch, cross-linked polyvinylpyrrolidone and sodium croscarmellose sodium. In particular, the disintegrant maybe croscarmellose sodium. The disintegrant maybe from 0.5 to 10% by weight of the composition. More particularly, it may be from 2 to 5% by weight of the composition.
• the lubricant or glidant may be one or more of fatty acids and their salts, colloidal silicon dioxide and talc. In particular, the lubricant is magnesium stearate and the glidant is colloidal silicon dioxide.
• the lubricant may be advantageously employed in an amount of from 0.05 to 3.0% by weight of the composition. More particularly, it may be from 0.2 to 2% by weight of the composition.
• the composition may be formulated in the form of granules filled in capsule, tablet or other suitable oral dosage form and, in particular, may be a tablet.
• the tablet formulation may further be coated.
• a process for preparing a pharmaceutical composition of moxifloxacin includes a) preparing an mtragranular portion by mixing moxifloxacin and at least one substantially water insoluble excipient; b) preparing an extragranular portion by mixing at least one substantially water insoluble excipient and other pharmaceutically accepted excipients; and c) compressing said mtragranular portion and extragranular portion to a tablet or filling said mtragranular portion and extragranular portion into a capsule.
• Embodiments of the process may include one or more of the following features.
• the mtragranular portion may further include other pharmaceutically accepted excipients.
• the other excipients may include one or more of binders, disintegerants, fillers, lubricants/glidants, and colorants.
• the substantially insoluble excipients may include one or more of microcrystalline cellulose, pregelatinized starch, dicalcium phosphate dibasic, corn starch, and the like.
• the binders may be one or more of polyvinyl pyrrolidone, hydroxypropyl cellulose and gums.
• the fillers may be one or more of cellulose derivatives, starch derivatives, sugars, sugar alcohols, and the like.
• the disintegrant may be one or more of pregelatinized starch, cross-linked polyvinylpyrrolidone and sodium croscarmellose sodium. In particular, the disintegrant maybe croscarmellose sodium. The disintegrant maybe from 0.5 to 10% by weight of the composition. More particularly, it may be from 2 to 5% by weight of the composition.
• the lubricant or glidant may be one or more of fatty acids and their salts, colloidal silicon dioxide and talc. In particular, the lubricant is magnesium stearate and the glidant is colloidal silicon dioxide.
• the lubricant may be advantageously employed in an amount of from 0.05 to 3.0% by weight of the composition. More particularly, it may be from 0.2 to 2% by weight of the composition.
• Avelox tablet formulations can be obtained by mtragranular and extragranular distribution of substantially water insoluble pharmaceutical excipients, with or without the inclusion of lactose.
• the formulation maybe in the form of granules filled in capsule, tablet or other suitable oral dosage form.
• moxifloxacin refers its free base, salts, solvates, enantiomers or mixtures thereof.
• the salts of moxifloxacin include, for example, acid addition salts, such as salts of hydrochloric acid, sulphuric acid, acetic acid, lactic acid, etc., and also salts with bases, such as sodium hydroxide, potassium hydroxide, etc. hi particular, the acid addition salt may be moxifloxacin hydrochloride monohydrate.
• acid addition salt may be moxifloxacin hydrochloride monohydrate.
• substantially insoluble refers to the solubility less than that of lactose.
• substantially insoluble excipients include microcrystalline cellulose, pregelatinized starch, dicalcium phosphate dibasic, corn starch, and the like.
• the mtragranular and extragranular portions may also contain other pharmaceutically acceptable excipients such as binders, disintegerants, fillers, lubricants/glidants, colorants, and the like.
• Suitable binders may include one or more of polyvinyl pyrrolidone, hydroxypropyl cellulose, gums and the like.
• Suitable fillers may include one or more of cellulose derivatives, starch derivatives, sugars, sugar alcohols and the like.
• Suitable disintegrants include one or more of pregelatinized starch, cross-linked polyvinylpyrrolidone, sodium croscarmellose sodium and the like. In particular, the disintegrant may be croscarmellose sodium.
• the pharmaceutical composition may contain from 0.5 to 10%, preferably from 2 to 5%, of the disintegrant.
• Suitable lubricants and glidants may include one or more of fatty acids and their salts, colloidal silicon dioxide, talc and the like.
• the lubricant is a salt of a fatty acid, for example, magnesium stearate.
• the glidant is colloidal silicon dioxide.
• the lubricant is advantageously employed in an amount of from 0.05 to 3.0%, for example, 0.2 to 2%.
• the colors maybe selected from any FDA approved colors for internal use.
• the formulation may optionally be coated.
• the dosage form may be in tablet or capsule form, however, the tablet form is particularly suitable.
• the tablet may further be coated.
• any formulation which is customary in pharmaceutical technology, such as, for example, those based on hydroxypropyl methyl cellulose (HPMC) and/or polyethylene glycol of various molecular weights may be used.
• HPMC hydroxypropyl methyl cellulose
• polyethylene glycol of various molecular weights
• the formulations prepared according to the present invention were found to be bioeqivalent to the Avelox tablet dosage form available in the US market by Bayer.
• the following data shows the phannacokinetic data of tablet formulation of present invention and Avelox tablet available in US market carried out in 12 healthy human volunteers.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Inorganic Chemistry (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Medicinal Preparation (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=34259939

Family Applications (1)

Country Status (3)

Families Citing this family (14)

Family Cites Families (2)

• 2004
  • 2004-09-03 WO PCT/IB2004/002875 patent/WO2005020998A1/en not_active Application Discontinuation
  • 2004-09-03 EP EP04769278A patent/EP1663226A1/de not_active Withdrawn
• 2006
  • 2006-03-27 ZA ZA200602497A patent/ZA200602497B/en unknown

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events