WO2006003587A2 - Formes posologiques solides pour administration orale a base de derives azabicyclo - Google Patents

Formes posologiques solides pour administration orale a base de derives azabicyclo Download PDF

Info

Publication number
WO2006003587A2
WO2006003587A2 PCT/IB2005/052104 IB2005052104W WO2006003587A2 WO 2006003587 A2 WO2006003587 A2 WO 2006003587A2 IB 2005052104 W IB2005052104 W IB 2005052104W WO 2006003587 A2 WO2006003587 A2 WO 2006003587A2
Authority
WO
WIPO (PCT)
Prior art keywords
dosage form
solid dosage
granules
compound
alpha
Prior art date
Application number
PCT/IB2005/052104
Other languages
English (en)
Other versions
WO2006003587A3 (fr
Inventor
Korlapati Venkateswara Rao
Pradeep Jai Rao Karatgi
Ayanampudi Sri Rama Murthy
Original Assignee
Ranbaxy Laboratories Limited
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 Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2006003587A2 publication Critical patent/WO2006003587A2/fr
Publication of WO2006003587A3 publication Critical patent/WO2006003587A3/fr

Links

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
    • A61K9/2004—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
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates

Definitions

  • the present invention relates to solid dosage forms for oral administration of an azabicyclo derivative or its pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs and metabolites; and processes for the preparation of such solid dosage forms, wherein the solid dosage forms have excellent content uniformity.
  • Compound (I) is a muscarinic receptor antagonist with high affinity towards M3 receptors and may be useful as a safe and effective therapeutic or prophylactic agent for the treatment or prophylaxis of an animal or a human suffering from a disease or disorder of the respiratory, urinary and gastrointestinal systems, wherein the disease or disorder is mediated through or associated with muscarinic receptors.
  • the diseases or disorders may include diseases or disorders of the (a) respiratory system such as bronchial asthma, chronic obstructive pulmonary disorders (COPD), pulmonary fibrosis, and the like; (b) urinary system which induce such urinary disorders as urinary incontinence, lower urinary tract symptoms (LUTS), etc.; and (c) gastrointestinal system such as irritable bowel syndrome, obesity, diabetes and gas ⁇ trointestinal hyperkinesis, and the like.
  • COPD chronic obstructive pulmonary disorders
  • pulmonary fibrosis and the like
  • urinary system which induce such urinary disorders as urinary incontinence, lower urinary tract symptoms (LUTS), etc.
  • gastrointestinal system such as irritable bowel syndrome, obesity, diabetes and gas ⁇ trointestinal hyperkinesis, and the like.
  • compound (I) Because of its high potency, compound (I) is therapeutically effective at micromolar concentrations and needs to be administered at a very low dosage level.
  • the dispensing of a drug at low dose involves many complexities at the op ⁇ erational level, e.g., formulating the dosage form.
  • a major problem is to achieve content uniformity in a solid preparation. Failure to maintain the uniformity of drug content, e.g., if uniformity is not strictly assured, may result in an unforeseen accident by overdose or end up delivering a sub-therapeutic dose.
  • One method for ensuring content uniformity of a low dose drug in a dosage form is by formulating the dosage form by wet granulation. Apart from ensuring content uniformity, wet granulation also provides better compressibility, improved flow properties, enhanced drug release and improved appearance. Being a wet process, wet granulation also reduces losses due to dust and minimizes exposure of the drug to the operator.
  • compositions of compound (I) having excellent content uniformity can be prepared by wet granulating a blend of excipients by a solution of compound (I).
  • a solid dosage form for oral administration comprising (2R)-(I alpha, 5 alpha, 6 alpha)-N-[3-azabicyclo[3.1.0] hexyl- 6-(aminomethyi)-yi] -2-hydroxy-2-cyclopentyl-2-phenyl acetamide hydrochloride [compound (I)] and a pharmaceutically acceptable carrier.
  • the solid dosage form has excellent content uniformity.
  • Embodiments of the solid dosage form may have one or more of the following features.
  • the solid dosage form may be prepared by granulating a blend of excipients with a solution of compound (I).
  • the pharmaceutically acceptable carrier may be one or more excipients selected from diluent, binder, disintegrant, lubricant and glidant.
  • the diluent may be one or more of lactose, dextrose, sucrose, fructose, maltose, mannitol, erythritol, sorbitol, xylitol, lactitol, microcrystalline cellulose, dicalcium phosphate, tribasic calcium phosphate, calcium sulphate and calcium carbonate.
  • the diluent may be present in an amount ranging from about 50% to about 95% by weight of the composition.
  • the binder may be one or more of corn starch, pregelatinised starch, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, car- boxy vinyl polymers and acrylates.
  • the binder may be present in an amount ranging from about 1% to about 15% w/w by weight of the composition.
  • the disintegrant may be one or more of cross-linked carboxymethylcellulose sodium, cross-linked polyvinylpyrrolidone, sodium starch glycolate, pregelatinized starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, low- substituted hydroxypropyl cellulose and alginates.
  • the disintegrant may be present in an amount ranging from about 1% to about 10% w/w by weight of the composition.
  • the lubricant may be one or more of talc, magnesium stearate, zinc stearate, calcium stearate, sodium stearyl fumarate and stearic acid.
  • the glidant may be one or more of talc and colloidal silicon dioxide.
  • the lubricant and/or glidant may be present in an amount ranging from about 0.1% to about 2% by weight of the composition.
  • the pharmaceutically acceptable carrier may further include one or more of sweetener, coloring agent and flavoring agent.
  • the solid dosage form may be a capsule or a tablet.
  • Embodiments of the process may include one or more of the features described above.
  • Embodiments of the process may include one or more of the features described above.
  • the process includes:
  • Embodiments of the process may include one or more of the features described above.
  • Embodiments of the process may include one or more of the features described above.
  • a method for treatment or prophylaxis of an animal or a human suffering from a disease or disorder of the respiratory, urinary or gastrointestinal systems mediated through or associated with muscarinic receptors comprising administering to the animal or human a solid dosage form of (2R)-(I alpha, 5 alpha, 6 alpha)-N-[3-azabicyclo [3.1.0] hexyl-6-(aminomethyl)-yl] - 2-hydroxy-2-cyclopentyl-2-phenyl acetamide hydrochloride [compound (I)] and a pharmaceutically acceptable carrier, wherein the solid dosage form has excellent content uniformity.
  • the solid dosage form may include one or more of the following features or the features described above.
  • the solid dosage form may be prepared by granulating a blend of excipients with a solution of compound (I).
  • the term 'compound (I)' as used herein includes pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs and metabolites of compound (I).
  • compound (I) is a hydrochloride salt, other water-soluble pharmaceutically acceptable salts can also or instead be used and are within the scope of this invention.
  • Compound (I) as described herein is used in a therapeutically effective amount in the solid dosage forms.
  • the term 'therapeutically effective amount' intends to describe a dose of compound (I) that is effective for the treatment or prophylaxis of a disease or disorder of the respiratory, urinary and/or gastrointestinal systems. The dose may range from 0.01 ⁇ g to 20 mg of compound (I) per unit dosage form.
  • the term 'content uniformity' or 'uniformity in content' as used herein is intended to describe solid dosage forms that pass the content uniformity test as described in the U.S. Pharmacopoeia (USP).
  • USP U.S. Pharmacopoeia
  • the USP states that 'the requirements for dosage uniformity are met if the amount of active ingredient in not less than 9 out of the 10 dosage units as determined by content uniformity method lies within the range of 85.0% to 115.0% of label claim and no unit is out side the range of 75.0% to 125.0% of the label claim and the relative standard deviation (RSD) of the 10 dosage units is less than or equal to 6.0%.
  • solid dosage forms as described herein are meant for oral administration and may be utilized in the form of granules, tablets or capsules. They may be ingested directly, or dispersed in water or other suitable vehicle prior to administration. Tablets may be of the rapidly disintegrating type, which disintegrate in the oral cavity, and can be taken with or without water. Capsules may be of the hard gelatin type.
  • the solid dosage forms as described herein may include pharmaceutically acceptable excipients, including diluents, binders, disintegrants, lubricants and glidants.
  • Diluents may be selected depending upon the compatibility with the active ingredient. Diluents that may be used include water-soluble as well as water-insoluble diluents or a mixture thereof. Water-soluble diluents may be exemplified, but are not limited to, saccharides like lactose, dextrose, sucrose, fructose, maltose; sugars like mannitol, erythritol, sorbitol, xylitol and lactitol; and the like.
  • Water-insoluble diluents may include but are not limited to cellulose derivatives like powdered cellulose, micro- crystalline cellulose, dicalcium phosphate, tribasic calcium phosphate, calcium sulphate, calcium carbonate and the like.
  • the diluent may be used in an amount ranging form about 50% to about 95% by weight of the solid dosage form.
  • Binders are generally used in a solid dosage form to impart cohesive properties to a powdered blend. Binders that may be used are selected from the group comprising starch derivatives like corn starch and pregelatinised starch, polyvinylpyrrolidone, hy- droxypropyl cellulose, hydroxypropyl methylcellulose, carboxyvinyl polymers like carbomers, acrylates like Eudragits and other such materials routinely used in the art of solid dosage form manufacturing.
  • the binder may be present in an amount varying from about 1% to about 15%, more particularly from about 5% to about 12% by weight of the solid dosage form.
  • Disintegrants play a major role in the disintegration of solid dosage forms.
  • the dis- integrant may be selected from cross-linked carboxymethylcellulose and its sodium salt, cross-linked polyvinylpyrrolidone, sodium starch glycolate, pregelatinized starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, low-substituted hy ⁇ droxypropyl cellulose, alginates and the like.
  • Particularly suitable disintegrants include cross-linked carboxymethylcellulose sodium.
  • the amount of the disintegrant may vary from 1% to 10% by weight of the solid dosage form.
  • Lubricants may be selected from the group consisting of talc, magnesium stearate, zinc stearate, calcium stearate, sodium stearyl fumarate and stearic acid.
  • Glidants may be selected from talc, colloidal silicon dioxide, and the like.
  • the lubricant and glidant may be used in a concentration of 0.1% to 2% by weight of the solid dosage form.
  • the solid dosage forms as described herein may also include additional excipients like sweeteners, flavoring agents and coloring agents.
  • the solution of compound (I) may be prepared in a solvent such as water or a mixture of water and a non-aqueous solvent.
  • Excipients consisting of one or more diluent, binder and disintegrant are blended in a rapid mixer granulator and the blend sub ⁇ sequently granulated with the solution of compound (I).
  • the mixture is kneaded until granulation is complete.
  • the granules are then dried in a fluid bed drier and passed through a screen of suitable size.
  • the dried granules are mixed with glidant and lubricant and either filled into capsules of suitable size or compressed into tablets using appropriate tooling. It was observed that partial granulation of the blend, so that a part of the excipient blend is converted into granules while a part is left ungranulated, yields tablets having rapid disintegration properties.
  • the ratio of the weight of blend to the weight of water is about 1:1.5 and more particularly about 1:1.1 to 1:1.2.
  • the bed is then granulated with the solution of compound (I) and the granules are dried and sized.
  • the dried granules are mixed with the glidant and lubricant and either filled into capsules of suitable size or compressed into tablets using appropriate tooling.
  • the granulation may also be carried out using a spray granulation technique in which the bed of excipients, as prepared above, is sprayed upon by a solution of compound (I).
  • the solution is atomized with the use of compressed air and spraying may be done using conventional equipments available, such as a spray gun.
  • the mixture is continuously agitated as the granulation advances.
  • the granules that are obtained are dried, sized and filled into capsules of suitable size or compressed into tablets using appropriate tooling.
  • Fluidized bed granulation may also be used for carrying out wet granulation.
  • the excipients consisting of one or more diluent, binder and disintegrant are introduced in the fluid bed granulator and fluidized.
  • the solution of compound (I) is sprayed onto the fluidized bed from the top against the air-flow by means of a spray nozzle.
  • a part of the binder in the form of a solution can additionally be sprayed to form granules.
  • the granules obtained are filled into capsules of suitable size or compressed into tablet using appropriate tooling.
  • capsules of compound (I) are prepared by dissolving compound (I) in water to form an aqueous solution; granulating a blend of diluent, binder and disintegrant with the solution; drying and sizing the granules; blending the granules with a lubricant and a glidant; and filling the granules in capsules of suitable size.
  • tablets of compound (I) are prepared by dissolving compound (I) in water to form an aqueous solution; granulating a blend of diluent, binder and disintegrant with the solution; drying and sizing the granules; blending the granules with a lubricant and a glidant; and compressing the granules into tablets using appropriate tooling.
  • tablets of compound (I) are prepared by dissolving compound (I) in water to form an aqueous solution; partially granulating a blend of diluent, disintegrant, binder and optionally a second diluent, coloring agent and flavoring agent with the solution so that a part of the excipient blend is converted into granules while a part is left ungranulated; drying the partially granulated excipient blend and further mixing with a diluent, disintegrant, lubricant, glidant, coloring agent and flavoring agent; and compressing the granules into tablets using appropriate tooling.
  • capsules of compound (I) are prepared by preparing a bed of excipients consisting of diluent, binder and disintegrant; wetting the bed with water; granulating the bed with an aqueous solution of compound (I) under continuous mixing; drying and sizing the granules; blending the granules with a lubricant and a glidant; and filling the granules in capsules of suitable size.
  • capsules of compound (I) are prepared by preparing a bed of excipients consisting of diluent, binder and disintegrant; preparing a solution of compound (I); atomizing and uniformly spraying the solution over the bed of excipients along with continuous mixing and agitation to form granules; drying and sizing the granules; blending the granules with a lubricant and a glidant; and filling the granules in capsules of suitable size.
  • a solid dosage form of compound (I) is prepared by preparing a bed of excipients consisting of diluent, binder and disintegrant in a fluidized bed granulator; spraying aqueous solution of compound (I) over the bed of excipients and granulating the blend partially; spraying a binder solution and granulating the mixture completely; sizing the granules; blending the granules with a lubricant and a glidant; and filling the granules in capsules of suitable size.
  • Example 7 [74] Procedure: The final blend prepared by the procedure as given above using the composition of Example 6 was compressed into tablets using appropriate tooling.
  • Example 10 [82] Procedure: The final blend prepared by the procedure as described in Example 9 was compressed into tablets using appropriate tooling.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des formes posologiques solides pour administration orale d'un dérivé azabicyclo ou de solvates, esters, énantiomères, diastéréo-isomères, N-oxydes, polymorphes et métabolites de celui-ci, acceptables d'un point de vue pharmaceutique, ainsi que des procédés pour préparer de telles formes posologiques solides. Lesdites formes posologiques solides sont caractérisées en ce qu'elles présentent une très bonne uniformité de teneur.
PCT/IB2005/052104 2004-07-01 2005-06-24 Formes posologiques solides pour administration orale a base de derives azabicyclo WO2006003587A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1234DE2004 2004-07-01
IN1234/DEL/2004 2004-07-01

Publications (2)

Publication Number Publication Date
WO2006003587A2 true WO2006003587A2 (fr) 2006-01-12
WO2006003587A3 WO2006003587A3 (fr) 2006-09-14

Family

ID=35124429

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2005/052104 WO2006003587A2 (fr) 2004-07-01 2005-06-24 Formes posologiques solides pour administration orale a base de derives azabicyclo

Country Status (1)

Country Link
WO (1) WO2006003587A2 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006117754A1 (fr) * 2005-05-03 2006-11-09 Ranbaxy Laboratories Limited Derives d'azabicyclo [3.1.0] hexane 3,6-disubstitues utilises comme antagonistes du recepteur muscarinique
WO2007045979A1 (fr) * 2005-10-19 2007-04-26 Ranbaxy Laboratories Limited Compositions pharmaceutiques d'antagonistes du recepteur muscarinique
WO2008075321A2 (fr) * 2006-12-21 2008-06-26 Ranbaxy Laboratories Limited Formulations à libération modifiée de dérivés azabicyclo
US7517905B2 (en) 2003-04-09 2009-04-14 Ranbaxy Laboratories Limited Substituted azabicyclo hexane derivatives as muscarinic receptor antagonists

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004005252A1 (fr) * 2002-07-08 2004-01-15 Ranbaxy Laboratories Limited Derives azabicyclo utilises comme antagonistes des recepteur muscariniques

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004005252A1 (fr) * 2002-07-08 2004-01-15 Ranbaxy Laboratories Limited Derives azabicyclo utilises comme antagonistes des recepteur muscariniques

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7517905B2 (en) 2003-04-09 2009-04-14 Ranbaxy Laboratories Limited Substituted azabicyclo hexane derivatives as muscarinic receptor antagonists
WO2006117754A1 (fr) * 2005-05-03 2006-11-09 Ranbaxy Laboratories Limited Derives d'azabicyclo [3.1.0] hexane 3,6-disubstitues utilises comme antagonistes du recepteur muscarinique
WO2007045979A1 (fr) * 2005-10-19 2007-04-26 Ranbaxy Laboratories Limited Compositions pharmaceutiques d'antagonistes du recepteur muscarinique
WO2008075321A2 (fr) * 2006-12-21 2008-06-26 Ranbaxy Laboratories Limited Formulations à libération modifiée de dérivés azabicyclo
WO2008075321A3 (fr) * 2006-12-21 2008-08-21 Ranbaxy Lab Ltd Formulations à libération modifiée de dérivés azabicyclo

Also Published As

Publication number Publication date
WO2006003587A3 (fr) 2006-09-14

Similar Documents

Publication Publication Date Title
EP1341527B1 (fr) Preparation pharmaceutique comprenant un principe actif disperse sur une matrice
JP6173521B2 (ja) ナルブフィンを含有する製剤及びそれらの使用
JP2023011888A (ja) 新たな医薬組成物
EP2136793B1 (fr) Formulations pour comprimés contenant des sels de 8-[{1-(3,5-bis- (trifluorométhyl)phényl)-éthoxy}-méthyl]-8-phényl-1,7-diaza-spiro[4,5]- décan-2-one et comprimés
JP4868695B2 (ja) 崩壊性が良好な経口製剤
TWI228414B (en) Pharmaceutical composition comprising carvedilol and hydrochlorothiazide, solid dosage form comprising it, and process for the production of the same
JP2001517616A (ja) 活性成分としてクロドロン酸塩および賦形剤としてケイ化微晶質セルロースを含む医薬製剤
AU2007338359B2 (en) Pharmaceutical formulation comprising neurokinin antagonist
EP1871363A1 (fr) Processus a etapes combinees pour compositions pharmaceutiques
AU2014315110A1 (en) Corticosteroid containing orally disintegrating tablet compositions for eosinophilic esophagitis
US20090017122A1 (en) Drug Forms Having Controlled Bioavailability
BR112021013976A2 (pt) Método para produção e uso de uma forma de dosagem de melatonina, e composição de melatonina micronizada sólida
WO2006003587A2 (fr) Formes posologiques solides pour administration orale a base de derives azabicyclo
CN114642639A (zh) 一种枸橼酸托法替布缓释组合物及其制备方法
CN114867469A (zh) 包含氨基甲酸酯化合物的口服药物组合物及其制备方法
JP2016079102A (ja) ソリフェナシン含有製剤
JP5132090B2 (ja) 塩酸エピナスチンドライシロップ剤
JP2018070541A (ja) ソリフェナシン含有医薬組成物とその製造方法
WO1999020277A1 (fr) Composition medicamenteuse a dissolution rapide
JP2021167306A (ja) 崩壊性粒子の製造方法
US20100152269A1 (en) Modified-release formulations of azabicyclo derivatives
WO2014157603A1 (fr) Composition pharmaceutique pour administration orale

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase in:

Ref country code: DE

WWW Wipo information: withdrawn in national office

Ref document number: DE

WWE Wipo information: entry into national phase

Ref document number: 722/DELNP/2007

Country of ref document: IN

122 Ep: pct application non-entry in european phase