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WO2001013889A1 - Composition pharmaceutique comprenant du nabumetone - Google Patents

Composition pharmaceutique comprenant du nabumetone Download PDF

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Publication number
WO2001013889A1
WO2001013889A1 PCT/GB2000/003312 GB0003312W WO0113889A1 WO 2001013889 A1 WO2001013889 A1 WO 2001013889A1 GB 0003312 W GB0003312 W GB 0003312W WO 0113889 A1 WO0113889 A1 WO 0113889A1
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WO
WIPO (PCT)
Prior art keywords
nabumetone
composition according
cmax
administration
hours
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/GB2000/003312
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English (en)
Inventor
Paul John Cummings
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.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham 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 SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Priority to JP2001518027A priority Critical patent/JP2003507409A/ja
Priority to EP00956670A priority patent/EP1207855A1/fr
Priority to AU68542/00A priority patent/AU6854200A/en
Publication of WO2001013889A1 publication Critical patent/WO2001013889A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K9/14—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • 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
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • 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

Definitions

  • This invention relates to a novel composition of nabumetone and to the use of this composition in the treatment of pain, osteoanh ⁇ tis and rheumatoid a ⁇ hritis.
  • Nabumetone 4-(6 " -methoxy-2 * -naphthyl)butan-2-one
  • Nabumetone has the following structure:
  • This compound is useful as an anti-inflammatory and has been approved for treating osteoa ⁇ hritis and rheumatoid a ⁇ hritis.
  • nabumetone can be formulated in a novel composition that has enhanced bioavailability and faster absorption. Also, this novel formulation can be used not only in the treatment of osteoa ⁇ hritis and rheumatoid a ⁇ hritis. but also in the treatment of pain.
  • the present invention is based on the finding that nabumetone has enhanced bioavailability in ce ⁇ ain compositions of controlled particle size.
  • the present invention provides a novel composition comprising nabumetone in paniculate form, said composition having a particle size distribution or nabumetone such that the median particle size is in the range of about 10 micrometers to about 0 55 micrometers
  • the present invention also provides a pharmaceutical composition comprising nabumetone wherein the active metabolite 6-MNA appears in plasma at about 20% of Cmax within 0 5 hours after administration, at about 50% of Cmax within 1 hour after administration, at about 80% of Cmax within 2 hours after administration and at about 90% of Cmax within 3 hours after administration.
  • the present invention provides a pharmaceutical composition comprising nabumetone wherein the dissolution rate for nabumetone is at about 100% ten minutes after administration
  • the present invention provides a pharmaceutical composition comprising nabumetone wherein the active metabolite 6-MNA provides a single dose Tmax which is significantly shorter, preferably by at least 2 hours and more preferably by at least 4 hours, and a Cmax which is significantly higher, preferably by at least 40% and more preferably by at least 70%. than tnat for ⁇ comparable dosage strength of commercial nabumetone
  • This invention also prov ides for the use of this novel composition in the treatment of pain, osteoarth ⁇ tis and rheumatoid arthritis
  • compositions compnsing nabumetone are provided with nabumetone in particulate form
  • the compositions are prepared using a process that involves a wet milling step in order to produce a particle size distribution of nabumetone wherein the median particle size is in the range of about 10 micrometers to about 0 55 micrometers
  • the paniculate suspension thus produced, is spray ⁇ ed using a spray dryer or granulated using a fluid bed granulator
  • the paniculate composition may then be formulated in the form of tablets, capsules, reconstitutable powders, semiso d products or supposito ⁇ es, or used directly in liquid form as an oral suspension or spray for local or buccal administration Orally administrate formulations are preferred.
  • the wet milling of nabumetone takes place in an aqueous medium containing one or more pharmaceutically acceptable water-soluble earners suitable for spray drying
  • the aqueous suspension contains a wetting agent to maintain the particles in suspension du ⁇ ng milling and to ensure their recovery following administration of the pharmaceutical formulation to a patient
  • Pharmaceutically acceptable excipients most suitable for spray-drying are water soluble hydroxypropylmethyl cellulose, a binder, and mannitol.
  • binders such as polyvinylpynohdone (PVP), hydroxypropyl cellulose (HPC , and methyl cellulose or other carbohydrates, such as sucrose, sorbitol, lactose, lactitol and xylitol and starch may also be used as a earner
  • PVP polyvinylpynohdone
  • HPC hydroxypropyl cellulose
  • methyl cellulose or other carbohydrates such as sucrose, sorbitol, lactose, lactitol and xylitol and starch
  • nabumetone may be present from about 20 to about 40% w/v
  • mav vary from about 2 to about 4% w/v of the composition to be milled
  • the amount of wetting agent mav be va ⁇ ed from about 0 1 to about 0 4% w/ ⁇ Preferably, it is present at about 0 3% w/v
  • a suitable wetting agent is sodium lauryl sulphate
  • compositions of this invention are most suitably prepared by wet milling nabumetone preferably using a bead mill, such as Nylacast Mill by Nylacast Ltd , Leicester, England Alternate milling equipment is available from Dena Systems BK and Netzsch
  • the milling medium consists of zirconium oxide beads Specifically, the mill chambers were loaded with YZT® ceramic beads manufactured from tt ⁇ a-stab ⁇ l ⁇ zed, high pu ⁇ ty zircoma powder (manufactured bv Ni kato Corporation Japan) The panicle size distributions of the suspension lormuiations were determined using a Malvern laser diffraction unit. Mastersizer S Model S4700. from Malvern Instruments Ltd , Malvem.
  • the median panicle size is in the range of about 10 micrometers to about 0 55 micometers
  • the median panicle size is about 1 8 to 0 8 micrometers
  • Sprav drying/fluid bed granulation of milled compositions is earned out most suitably using a spray dr er, such as a NIRO SD 63R Spray Dryer or a Yamato GA-32 Spray Dryer [Yamato Scientific Ame ⁇ ca Inc . Orangeburg, NY], or a fluid bed granulator, such as Glatt fluid bed granulator
  • a wet milling process is used to improve the bioa ailabihtv and the therapeutic efficacy of the poorly water soluble drug nabumetone
  • a DENA Bead Mill was used to reduce the panicle size distribution of the commercially available nabumetone drug substance
  • Nabumetone is preferably wet milled as an aqueous dispersion
  • the compound may be milled in any suitable non-aqueous or organic solvent, e g an oil
  • the wet milling of nabumetone in an aqueous medium could include one or more excipients. such as a soluble earner suitable for freeze or spray drying, a surfactant to maintain the particles in suspension, and one or more anti-agglomeration/suspending agents
  • excipients such as a soluble earner suitable for freeze or spray drying, a surfactant to maintain the particles in suspension, and one or more anti-agglomeration/suspending agents
  • An especially suitable excipient for spray-drying is mannitol.
  • the panicle size dist ⁇ bution was measured using a Malvern Mastersizer S laser diffraction unit. The prefened method of reporting the particle size dist ⁇ bution is to quote parameters such as D(0 I ). D(0 5 ), and D(0 9).
  • D(0.1 ) represents the size ( as equivalent volume diameter) below w hich 10% of the panicles lie.
  • D(0 5) is the size below which 50% of the panicles he. also known as the median D(0.9) is the value below which 90% of the particles lie.
  • the aqueous paniculate suspension could be further formulated for use as a paediat ⁇ c/adult strength suspension
  • the suspensions containing mannitol are ideal for pou ⁇ ng into a pre-formed blister and freeze-drymg to make a tablet.
  • the prefened method of production for nabumetone is to dry the suspension to a powder by spray drying. Since nabumetone has a melting point of 80 degrees C.
  • the spray d ⁇ ed powder is produced using relatively low temperatures
  • the spray dryer was pre-heated until the inlet temperature was at 100 degrees C. and the outlet temperature reached 35-40 degrees C.
  • a powder composition containing the paniculate nabumetone is obtainable as a composition which has good flowabi ty and is suitable for incorporation into capsules or tablet formulations. This result is surp ⁇ smg since one skilled in the art would not expect that a satisfactory spray d ⁇ ed product would be produced at such low temperatures from an aqueous system.
  • Tablets and capsules for oral administration are usually presented in a unit dose. and contain conventional excipients such as binding agents, fillers and diluents (tableting or compression aids ), lubricants, disintegrants. colorants, flavou ⁇ ngs. and wetting agents
  • excipients such as binding agents, fillers and diluents (tableting or compression aids ), lubricants, disintegrants. colorants, flavou ⁇ ngs. and wetting agents
  • the tablets may be coated according to techniques well known in the art
  • the solid oral formulations may be prepared by conventional methods of blending, filling , tableting , and the like. Repeated blending operations may be used to dist ⁇ bute the active agent throughout those compositions employing large quantities of fillers Such operations are, of course, well known in the art. Oral formulations also include conventional controlled release formulations, such as tablets or pellets, beads or granules, having a sustained release or an ente ⁇ c coating , or otherwise modified to control the release of the active compound, for example by the inclusion of gel forming polymers or matrix forming waxes.
  • a wetting agent is included in the composition to facilitate uniform dist ⁇ bution of the compound of the invention.
  • the present invention provides a novel composition which comprises nabumetone.
  • the composition is adapted for oral administration.
  • the composition is presented as a unit dose. Such a composition is taken preferably from 1 to 4 times daily.
  • the prefened unit dosage forms include tablets or capsules.
  • the oral dose is about 450-2250 mg.
  • the oral dose is 1350 mg given once daily.
  • Nabumetone is a pro-drug that is metabolised by the liver to form the active compound 6-methoxy-2-naphthyiacetic acid (6-MNA).
  • 6-MNA 6-methoxy-2-naphthyiacetic acid
  • non-disintegrating disks were prepared by compressing the nabumetone spray dried powder. Dissolution testing was conducted on these disks in 2% sodium lauryl sulphate maintained at 37 degrees C. Unmilled nabumetone and a blend of unmilled nabumetone containing equivalent quantities of the excipients required for the milling process were compressed and used as controls. A significant increase in the dissolution profile of the spray dried DENA milled nabumetone was observed.
  • a clinical trial was conducted to establish the effect of the increased dissolution rate of nabumetone observed in-vitro on the bioavailability of 6-MNA in-vivo.
  • the trial evaluated the bioavailability of 6-MNA from a single dose of nabumetone administered in capsules containing paniculate nabumetone relative to capsules containing regular commercial material.
  • the present invention provides a pharmaceutical composition comprising nabumetone wherein the active metabolite 6-MNA appears in plasma at about 20% of
  • Cmax within 0.5 hours after administration at about 50% of Cmax within 1 hour after administration, at about 80% of Cmax within 2 hours after administration and at about 90% of Cmax within 3 hours after administration.
  • the present invention provides a pharmaceutical composition comprising nabumetone wherein the dissolution rate for nabumetone is at about 100% ten minutes after administration. Furthermore, the present invention provides a pharmaceutical composition compnsing nabumetone wherein the active metabolite 6-MNA provides a single dose Tmax which is significantly shorter, preferably by at least 2 hours and more preferably by at least 4 hours, and a Cmax which is significantly higher, preferably by at least 40% and more 5 preferably by at least 70%. than that for a comparable dosage strength of commercial nabumetone
  • Nabumetone is useful in the treatment of pain, osteoarth ⁇ tis and rheumatoid 10 arth ⁇ tis
  • nabumetone is useful in controlling fever, in the prevention and treatment of colon cancer and in the prevention and treatment of Alzheimer s disease
  • the instant composition containing nabumetone in particulate form is useful in the treatment of pain
  • HPMC and SLS were blended and the nabumetone drug substance added in equal volumes to ensure a homogeneous blend
  • the suspension was transfened to a calibrated container and made up to the appropriate volume ( 1 -2 litres).
  • the suspension was poured gradually into the mill reservoir.
  • the suspension was then pumped through the D3 reactor into milling chamber 1. through a heat exchanger, into milling chamber 2. through a second heat exchanger and into the S 1 &. SS reactors before returning to the reservoir where the milling cycle was continued for 60 minutes.
  • a sample of the milled suspension was taken from the reservoir every 10 minutes for panicle size analysis. After milling the resulting suspensions were stored at 5 degrees C Sprav drving
  • Mannitol (Grade fine 60) was blended with the milled suspension in a ratio of 2 parts drug to 1 part mannitol using a Heidolph mixer
  • the spray dryer was pre-heated (inlet temperature 100 degrees C. outlet temperature 35 degrees C. exhaust fan setting 2)
  • the milled drug slurry was then slowly pumped througn the atomiser under -6 bar pressure and the resulting dried spheres were collected in an appropriate vessel
  • Particle Sizing Particle sizing of the initial nabumetone sample, the unmilled suspensions, the milled suspensions and the spray dried milled particles was earned out using a Malvern Mastersizer S (using the standard Mie theory without nabumetone refractive index conection to calculate the panicle size) where tne sample was dispersed in water
  • Dissolution testing on Formula A was earned out in 900 ml, 2% SLS at 37 degrees C using USP paddle apparatus at 100 rpm
  • the dissolution of lg powder samples and lg non- disintegrating disks was investigated
  • Non-disintegrating disks were prepared by compressing l g powder in an IR press under 7 ton pressure for 1 minute
  • Unmilled nabumetone and a blend of unmilled nabumetone containing equivalent quantities of the excipients required for the milling process were used as controls
  • the D(0 1). D(0 50) and D(0 9) values for the clinical particulate nabumetone after a two hour milling time were 0 28*, 0 61 * and 2 02* microns, respectively (* standard Mie theory not co ⁇ ected for nabumetone refractive index)
  • the median particle size D(0 5) value quoted on the Certificate of Analysis of the commercial nabumetone used in the comparator formulation was 29* microns (* standard Mie theory not co ⁇ ected for nabumetone refractive index)
  • Figure 1 shows a significant reduction in the panicle size distribution of nabumetone w as achieved within 10 minutes of processing
  • the co ⁇ esponding increase in the specific su ⁇ ace area of the panicles is shown in Figure 2
  • Figure 3 Further milling continued to decrease the particle size distribution of nabumetone
  • Figure 3 The level of drug loading or suspending agent present in the initial suspension did not affect the size dist ⁇ bution of the nabumetone particles produced, and the milling process was very reproducible
  • Figure 4 shows the percentage of nabumetone released as a function or time for v arious milled/unmilled nabumetone powder blends
  • the sprav dried Dena milled blend demonstrated the most rapid dissolution
  • An improvement in the dissolution oi nabumetone in the presence of the hvdrophilic excipients used in the milling/drv ing process was also observed
  • a significant increase in the dissolution profile of the spray d ⁇ ed Dena milled nabumetone was observed when the powder blends were compressed into non- disintegrating disks (Figure 5)
  • Figure 6 shows the mean plasma concentration time profiles for 6-MNA following a single oral administration of 501 mg of nabumetone as a formulation containing commercial or paniculate nabumetone to healthv volunteers
  • Formula A 0.48* microns
  • Formula D 0.50* microns ( * standard Mie theory not co ⁇ ected for nabumetone refractive index )
  • nabumetone spray dried powder 80.1 % w/w Table 5"
  • Nabumetone wet bead milled suspension 30.0% w/w
  • the suspension was pumped from the mixing vessel through the single pass five chambered DENA DS 15P wet bead mill. Each chamber was filled with the required volume and size of wear resistant yttria stabilised zirconia beads. The milled suspension was collected in 50L blue plastic Bowater Mauser kegs and held overnight for spray drying.
  • the milled suspension was charged to the feed vessel and pumped to the NIRO SD 6.3R spray drier.
  • the spray dried powder was collected in stainless steel bins, transfened individually into liners and packed in Bowater Mauser kegs containing desiccant (225g 3 A molecular sieve).
  • the NIRO SD 6.3R spray drying parameters are listed below:
  • Table 9 The mean ( ⁇ sd) Malvern Mastersizer S particle sizing data of Nabumetone 30 % suspension taken from the end product line. ( Mean of sizing data from samples taken start, middle and end of batch)
  • Nabumetone spray d ⁇ ed powder is screened using a 1 mm screen
  • the sodium starch glycolate and magnesium stearate are screened through 0 5 micron screen
  • the dry mate ⁇ als are blended in a bin blender and then compressed on a rotary tablet press

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Rheumatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

GB003312nte invention concerne une nouvelle composition qui comprend du nabumétone sous forme de particules et des techniques d'utilisation de cette composition pour traiter des douleurs, l'arthrose et l'arthrite rhumatoïde.
PCT/GB2000/003312 1999-08-25 2000-08-25 Composition pharmaceutique comprenant du nabumetone Ceased WO2001013889A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2001518027A JP2003507409A (ja) 1999-08-25 2000-08-25 ナブメトンを含んでなる医薬組成物
EP00956670A EP1207855A1 (fr) 1999-08-25 2000-08-25 Composition pharmaceutique comprenant du nabumetone
AU68542/00A AU6854200A (en) 1999-08-25 2000-08-25 Pharmaceutical composition comprising nabumetone

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9920148.5A GB9920148D0 (en) 1999-08-25 1999-08-25 Novel composition
GB9920148.5 1999-08-25

Publications (1)

Publication Number Publication Date
WO2001013889A1 true WO2001013889A1 (fr) 2001-03-01

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PCT/GB2000/003312 Ceased WO2001013889A1 (fr) 1999-08-25 2000-08-25 Composition pharmaceutique comprenant du nabumetone

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EP (1) EP1207855A1 (fr)
JP (1) JP2003507409A (fr)
AU (1) AU6854200A (fr)
GB (1) GB9920148D0 (fr)
WO (1) WO2001013889A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002000196A3 (fr) * 2000-06-28 2002-06-27 Smithkline Beecham Plc Procede de broyage par voie humide
WO2008007150A1 (fr) * 2006-07-13 2008-01-17 Unilever Plc Préparation de compositions pharmaceutiques
EP1900736A1 (fr) 2001-11-20 2008-03-19 Smithkline Beecham Plc 5-[4-[2-(n-methyl-n-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione et compositions pharmaceutiques contenant ce composé
US7857247B2 (en) 2005-08-12 2010-12-28 Brian Sulaiman Milling system

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100715355B1 (ko) * 2005-09-30 2007-05-07 주식회사유한양행 프란루카스트를 함유하는 분무-건조 과립 및 그의 제조방법

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993014747A1 (fr) * 1992-01-29 1993-08-05 Smithkline Beecham Plc Nabumetone refroidi par pulverisation
US5518738A (en) * 1995-02-09 1996-05-21 Nanosystem L.L.C. Nanoparticulate nsaid compositions
WO1996024336A1 (fr) * 1995-02-10 1996-08-15 Nanosystems L.L.C. Nanoparticules de medicaments anti-inflammatoires non steroidiens
WO2000037169A1 (fr) * 1998-12-21 2000-06-29 Smithkline Beecham Plc Procede et appareil de production d'articles a l'aide d'un fluide supercritique
WO2000053282A1 (fr) * 1999-03-10 2000-09-14 Smithkline Beecham P.L.C. Procede de cristallisation destine a la production de produits a cristaux surfins

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993014747A1 (fr) * 1992-01-29 1993-08-05 Smithkline Beecham Plc Nabumetone refroidi par pulverisation
US5518738A (en) * 1995-02-09 1996-05-21 Nanosystem L.L.C. Nanoparticulate nsaid compositions
WO1996024336A1 (fr) * 1995-02-10 1996-08-15 Nanosystems L.L.C. Nanoparticules de medicaments anti-inflammatoires non steroidiens
WO2000037169A1 (fr) * 1998-12-21 2000-06-29 Smithkline Beecham Plc Procede et appareil de production d'articles a l'aide d'un fluide supercritique
WO2000053282A1 (fr) * 1999-03-10 2000-09-14 Smithkline Beecham P.L.C. Procede de cristallisation destine a la production de produits a cristaux surfins

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002000196A3 (fr) * 2000-06-28 2002-06-27 Smithkline Beecham Plc Procede de broyage par voie humide
CZ303572B6 (cs) * 2000-06-28 2012-12-12 Smithkline Beecham P. L. C. Jemne rozmelnený prostredek a zpusob jeho prípravy
EP1900736A1 (fr) 2001-11-20 2008-03-19 Smithkline Beecham Plc 5-[4-[2-(n-methyl-n-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione et compositions pharmaceutiques contenant ce composé
US7857247B2 (en) 2005-08-12 2010-12-28 Brian Sulaiman Milling system
WO2008007150A1 (fr) * 2006-07-13 2008-01-17 Unilever Plc Préparation de compositions pharmaceutiques
US7691873B2 (en) 2006-07-13 2010-04-06 Conopco, Inc. Preparation of pharmaceutical formulations
US8945626B2 (en) 2006-07-13 2015-02-03 Andrew James Elphick Preparation of pharmaceutical compositions

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Publication number Publication date
JP2003507409A (ja) 2003-02-25
EP1207855A1 (fr) 2002-05-29
AU6854200A (en) 2001-03-19
GB9920148D0 (en) 1999-10-27

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