WO2016157061A1 - Procédé de broyage humide aseptique pour le palmitate de palipéridone - Google Patents

Procédé de broyage humide aseptique pour le palmitate de palipéridone Download PDF

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Publication number
WO2016157061A1
WO2016157061A1 PCT/IB2016/051734 IB2016051734W WO2016157061A1 WO 2016157061 A1 WO2016157061 A1 WO 2016157061A1 IB 2016051734 W IB2016051734 W IB 2016051734W WO 2016157061 A1 WO2016157061 A1 WO 2016157061A1
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Prior art keywords
paliperidone palmitate
milling
μιη
particle size
beads
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PCT/IB2016/051734
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English (en)
Inventor
Mukesh Kumar
Suhas KAKADE
Sopan PHAPAL
Prashant BIRANGAL
Varsha AWALE
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Wockhardt Limited
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Publication of WO2016157061A1 publication Critical patent/WO2016157061A1/fr

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    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds

Definitions

  • the invention relates to a process for micronizing paliperidone palmitate aseptically using wet milling.
  • the aseptic wet milling process uses two types of milling beads sequentially in single equipment to obtain particles of micronized paliperidone palmitate with desired size ranges and having uniform size distribution.
  • Paliperidone palmitate is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives with the chemical name (9RS)-3-[2-[4(6-Fluoro-1 ,2- benzisoxazol-S-y piperidin-l -yllethyll ⁇ -methyl- ⁇ oxo-ej ⁇ -tetrahydro- 4Hpyrido[1 ,2-a]pyrimadin-9-yl hexadecanoate. Its molecular formula is C39H57FN4O4 and its molecular weight is 664.89. The structural formula is:
  • the injection composition of paliperidone palmitate is available commercially and marketed under the brand name of Invega Sustena ® in US market. It is available as a white to off-white sterile aqueous extended-release suspension for intramuscular injection in dose strengths of 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg of paliperidone.
  • the composition is provided in a prefilled syringe (cyclic- olefin-copolymer) with a plunger stopper and tip cap (bromobutyl rubber).
  • sterile micronization of active ingredient is carried out in air-jet mills fitted in isolators. Jet mills can be operated in sterile conditions by integrating the mill in an isolator or a restricted access barrier system (RABS).
  • RABS restricted access barrier system
  • US Patent No. 6,555,544 discloses a process for preparing submicron particles of an antipsychotic agent.
  • the inventors of the invention surprisingly found that the sterile micronization of paliperidone palmitate by air-jet milling can be avoided and instead as an alternative, less expensive wet media milling can be used to produce particles with desired size range in a single equipment.
  • the inventors of the invention unexpectedly found that the processing time for reducing the particle size of paliperidone palmitate was reduced significantly by utilizing two types of milling beads sequentially.
  • the invention uses wet milling process in such a way that it produces particles of micronized paliperidone palmitate having an effective average particle size of less than 3 ⁇ and having narrow size distribution range. Moreover, the wet milling process may reduce the time to achieve desired particle size.
  • step (b) subjecting the premix of step (a) to wet milling in the presence of first milling beads having size of about 1 .5 mm to obtain a suspension of paliperidone palmitate with reduced effective average particle size;
  • step (c) subjecting the suspension formed in step (b) to wet milling in the presence of second milling beads having size of about 0.3 mm to obtain suspension of micronized paliperidone palmitate having effective average particle size of less than 3 ⁇ ,
  • the process is carried out as a batch processing.
  • the process of wet milling for micronizing paliperidone palmitate wherein the first milling beads reduce the particle size of paliperidone palmitate to an effective average particle size of less than about 40 ⁇ .
  • the particle size is reduced to an effective average particle size of less than about 30 ⁇ , more preferably less than about 20 ⁇ and yet more preferably less than about 10 ⁇ .
  • the process of wet milling for micronizing paliperidone palmitate, wherein the size of first type of milling beads ranges from 0.5 mm to 2.5 mm.
  • the process of wet milling for micronizing paliperidone palmitate wherein the size of second type of milling beads ranges from 0.15 mm to 0.45 mm.
  • the process of wet milling for micronizing paliperidone palmitate wherein the milling beads are made up of material selected from zirconium oxide, yttrium-stabilized zirconium oxide, steel, ceramic material, copper, silicon carbide, porcelain, quartz, aluminum oxide, non-ferrous metal or in special cases of plastics material.
  • a process for micronizing paliperidone palmitate aseptically using wet milling comprising steps of:
  • step (b) subjecting the premix of step (a) to wet milling in the presence of first milling beads to obtain a suspension of paliperidone palmitate particles with reduced effective average size in the range of about 10 to about 39 ⁇ ;
  • step (c) subjecting the suspension formed in step (b) to wet milling in the presence of second milling beads to obtain particles of paliperidone palmitate with effective average size of less than 3 ⁇ ,
  • the process of wet milling for micronizing paliperidone palmitate wherein the 1/4 th particle size reduction takes place in 2/3 of the total processing time when compared to wet media milling by single type of milling beads as against two types of milling beads.
  • the process of wet milling for micronizing paliperidone palmitate wherein the second milling beads reduce the particle size of paliperidone palmitate to an effective average particle size of less than 3 ⁇ .
  • the process of wet milling for micronizing paliperidone palmitate wherein the polydispersity index of the particles of paliperidone palmitate obtained is below 2.0.
  • the polydispersity index of the particles of paliperidone palmitate obtained is below 1 .9, more preferably below 1 .8, more preferably below 1 .7, more preferably below 1 .6 and yet more preferably about 1 .5.
  • dgo means that 10% of the said substance by volume has a particle size over the value stated with d 90 and the other 90% of the substance by volume has a particle size below the value stated with d 90 .
  • D 90 value can be measured by one of the known measuring devices, for instance by a device which measures particle distribution by laser diffraction, for instance, by Malvern Mastersizer.
  • polydispersity index refers to a measure of the distribution of particle sizes for a collection of particles.
  • PDI can be measured by one of the known measuring devices, for instance by a device which measures particle distribution by laser diffraction, for instance, by Malvern Mastersizer.
  • wet milling as used herein is intended to mean the grinding of materials with a sufficient quantity of a liquid to form a slurry. The process of wet milling and apparatus therefore are conventionally known in the art and do not form a critical feature of the invention.
  • the “milling beads” in the method of the invention preferably are chemically inert and rigid.
  • the term “chemically-inert”, as used herein, means that the milling beads do not react chemically with the biologically active compound or the grinding compound.
  • the milling beads are essentially resistant to fracture and erosion in the milling process.
  • the milling beads are desirably provided in the form of beads which have smooth ovoid or spherical shapes.
  • the milling beads are provided in the form of one or more of beads, balls or spheres.
  • the milling beads may be made for example of zirconium oxide, yttrium- stabilized zirconium oxide, steel, ceramic material, copper, silicon carbide, porcelain, quartz, aluminum oxide, non-ferrous metal or in special cases of plastics material.
  • the term "aseptic” is used interchangeably with the word “sterile”.
  • the aseptic processing or fabrication complies with GMP (Good Manufacturing Practice) industry guidelines such as those associated with Guidance for Industry— Sterile Drug Products Produced by Aseptic Processing— Current Good Manufacturing Practice, U.S. Department of Health and Human Services Food and Drug Administration, September 2004.
  • a process of wet milling for micronizing paliperidone palmitate which process employs two types of milling beads namely first type of milling beads and second type of milling beads.
  • the process of wet milling for micronizing paliperidone palmitate said process is carried out as a batch processing employing two types of milling beads sequentially.
  • the process of wet milling for micronizing paliperidone palmitate comprises first milling beads, wherein the size of first type of milling beads ranges from about 0.5 mm to about 2.5 mm.
  • the process of wet milling for micronizing paliperidone palmitate comprises second milling beads, wherein the size of second type of milling beads ranges from about 150 ⁇ to about 450 ⁇ .
  • the process of micronizing paliperidone palmitate aseptically using wet milling wherein the milling process is carried out at 50-3000 rpm.
  • step (b) subjecting the premix of step (a) to wet milling in the presence of first milling beads to obtain a suspension of paliperidone palmitate with reduced effective average particle size;
  • step (c) subjecting the suspension formed in step (b) to wet milling in the presence of second milling beads to obtain suspension of paliperidone palmitate having effective average particle size of less than 3 ⁇ ,
  • the process of wet milling for micronizing paliperidone palmitate wherein the micronized paliperidone palmitate particles have effective average particle size of less than 3 ⁇ .
  • having effective average particle size less than 2.9 ⁇ , more preferably less than 2.7 ⁇ , more preferably less than 2.5 ⁇ , more preferably less than 2.3 ⁇ , yet more preferably less than 2.1 ⁇ and yet more preferably about 2.0 ⁇ .
  • the process of wet milling for micronizing paliperidone palmitate wherein the processing with first milling beads and second milling beads constitute less than 4 hr.
  • processing with first milling beads and second milling beads constitute less than 3.5 hr, more preferably, less than 3 hr and yet more preferably less than 2 hr.
  • the process of wet milling for micronizing paliperidone palmitate wherein the processing with first milling beads and second milling beads constitute about 2 hr.
  • the process of wet milling for micronizing paliperidone palmitate wherein the processing with first milling beads is effected for the 1/4 th to 3/4 th of the total processing time.
  • the process of wet milling for micronizing paliperidone palmitate wherein the processing with second milling beads is effected for the 1/4 th to 3/4 th of the total processing time.
  • the process of wet milling for micronizing paliperidone palmitate wherein the processing with first milling beads is effected for about 30 min and processing with second milling beads is effected for about 1 hr and 30 min.
  • the process of wet milling for micronizing paliperidone palmitate wherein the processing with first milling beads is effected for about 1 hr and processing with second milling beads is effected for about 1 hr.
  • the process of wet milling for micronizing paliperidone palmitate wherein the processing with first milling beads is effected for about 1 hr 30 min and processing with second milling beads is effected for about 30 min.
  • the process of wet milling for micronizing paliperidone palmitate wherein the 1/4 th particle size reduction takes place in 2/3 rd of the total processing time when compared to wet media milling by single type of milling beads as against two types of milling beads, sequentially.
  • the polydispersity index of the micronized paliperidone palmitate is below 2.0.
  • the polydispersity index of the micronized paliperidone palmitate particles is below 1 .9, more preferably below 1 .8, more preferably below 1 .7, more preferably below 1 .6 and yet more preferably about 1 .5.
  • the process of wet milling for micronizing paliperidone palmitate wherein the size of first type of milling beads ranges from 0.5 mm to 2.5 mm.
  • the process of wet milling for micronizing paliperidone palmitate wherein the size of second type of milling beads ranges from 0.15 mm to 0.45 mm.
  • the process of wet milling for micronizing paliperidone palmitate wherein the milling beads are made up of material selected from the group consisting of zirconium oxide, yttrium-stabilized zirconium oxide, steel, ceramic material, copper, silicon carbide, porcelain, quartz, aluminum oxide, non-ferrous metal or in special cases of plastics material.
  • step (b) subjecting the premix of step (a) to wet milling in the presence of first milling beads having size of about 1 .5 mm to obtain a suspension of paliperidone palmitate with reduced effective average particle size range of about 10 ⁇ to 39 ⁇ ;
  • step (c) subjecting the suspension formed in step (b) to wet milling in the presence of second milling beads having size of about 0.3 mm to obtain suspension of micronized paliperidone palmitate having effective average particle size of less than 3 ⁇ ,
  • step (b) subjecting the premix of step (a) to wet milling in the presence of first milling beads having size of about 1 .5 mm to obtain a suspension of paliperidone palmitate with reduced effective average particle size range of about 10 ⁇ to 39 ⁇ ;
  • step (c) subjecting the suspension formed in step (b) to wet milling in the presence of second milling beads having size of about 0.3 mm to obtain suspension of paliperidone palmitate having effective average particle size of about 2 ⁇ , wherein the total process is carried out in single equipment aseptically.
  • the process of wet milling for micronizing paliperidone palmitate wherein the first milling beads reduce the particle size of paliperidone palmitate to an effective average particle size of less than 39 ⁇ .
  • the particle size is reduced to an effective average particle size of less than 30 ⁇ , more preferably less than 20 ⁇ , more preferably less than 15 ⁇ and yet more preferably less than 10 ⁇ .
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the obtained particles are having average particle size below 3.0 ⁇ .
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the particles having average particle size below 1 .2 ⁇ are obtained after 4 hr of batch processing.
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the particles having average particle size below 1 .2 ⁇ are obtained after 4 hr of batch processing.
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the particles having average particle size below 1 .2 ⁇ are obtained after 4 hr of batch processing.
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the particles having average particle size below 1 .2 ⁇ are obtained after 4 hr of batch processing.
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the particles having average particle size below 1 .2 ⁇ are obtained after 4 hr of batch processing.
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the particles having average particle size of about 2.0 ⁇ are obtained after about 2 hr of batch processing.
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the particles having average particle size of about 2.0 ⁇ are obtained after 2 hr of batch processing in which processing with first milling beads is effected for about 30 min and processing with second milling beads is effected for about 1 hr and 30 min.
  • the process of wet milling for aseptically micronizing paliperidone palmitate wherein the particles having average particle size of about 2.0 ⁇ are obtained after 2 hr of batch processing in which processing with first milling beads is effected for about 1 hr 30 min and processing with second milling beads is effected for about 30 min.
  • a process of wet milling for aseptically preparing a composition comprising micronized paliperidone palmitate and at least one pharmaceutically acceptable excipient.
  • the process of wet milling for aseptically preparing a composition comprising micronized paliperidone palmitate, a surfactant and at least one pharmaceutically acceptable excipient.
  • the process of wet milling for aseptically preparing a composition comprising micronized paliperidone palmitate, polysorbate 20, citric acid monohydrate, disodium hydrogen phosphate anhydrous, polyethylene glycol 4000, sodium dihydrogen phosphate monohydrate, sodium hydroxide, and water for injection.
  • the process of wet milling for aseptically preparing composition comprising:
  • the process of wet milling for aseptically preparing composition comprising:
  • composition comprising micronized paliperidone palmitate obtained by a process comprising steps of:
  • step (b) subjecting the premix of step (a) to mechanical means in the presence of first milling beads to obtain a suspension of paliperidone palmitate with reduced effective average particle size range of about 10 ⁇ to 39 ⁇ ;
  • step (c) subjecting the suspension formed in step (b) to mechanical means in the presence of second milling beads to obtain suspension of paliperidone palmitate having effective average particle size of about 2 ⁇ ,
  • Unmicronized Paliperidone palmitate (sterile grade) was dispersed into the polysorbate solution.
  • the suspension was milled aseptically in the grinding chamber using Yttrium stabilized zirconium beads (1 .5mm) till required particle size was reached.
  • the suspension was filtered aseptically through a 40 micron filter into a sterilized SS container.
  • Water for injections was transferred into a separate SS container, citric acid monohydrate, disodium hydrogen phosphate anhydrous, sodium dihydrogen phosphate monohydrate, sodium hydroxide, polyethylene glycol 4000 were added and mixed until dissolved.
  • This solution was sterilized by filtration through sterile 0.22 micron filter and transferred aseptically into milled suspension.
  • the final suspension was mixed until homogeneous.
  • the suspension was filled aseptically into sterile syringes.
  • Micronized Paliperidone palmitate (sterile grade) was dispersed into the polysorbate solution.
  • the suspension was milled aseptically in the grinding chamber using Yttrium stabilized zirconium beads (1 .5mm) till required particle size was reached.
  • the suspension was filtered aseptically through a 40 micron filter into a sterilized SS container.
  • Water for injections was transferred into a separate SS container, citric acid monohydrate, disodium hydrogen phosphate anhydrous, sodium dihydrogen phosphate monohydrate, sodium hydroxide, polyethylene glycol 4000 were added and mixed until dissolved.
  • This solution was sterilized by filtration through sterile 0.22 micron filter and transferred aseptically into milled suspension.
  • the final suspension was mixed until homogeneous.
  • the suspension was filled aseptically into sterile syringes.
  • Micronized Paliperidone palmitate (sterile grade) having was dispersed into the polysorbate solution.
  • the suspension was milled aseptically in the grinding chamber using Yttrium stabilized zirconium beads (0.3mm) till required particle size was reached.
  • the suspension was filtered aseptically through a 40 micron filter into a sterilized SS container.
  • Water for injections was transferred into a separate SS container, citric acid monohydrate, disodium hydrogen phosphate anhydrous, sodium dihydrogen phosphate monohydrate, sodium hydroxide, polyethylene glycol 4000 were added and mixed until dissolved.
  • This solution was sterilized by filtration through sterile 0.22 micron filter and transferred aseptically into milled suspension.
  • the final suspension was mixed until homogeneous.
  • the suspension was filled aseptically into sterile syringes.
  • Unmicronized Paliperidone palmitate (sterile grade) was dispersed into the polysorbate solution.
  • the suspension was milled aseptically in the grinding chamber using first milling beads (Yttrium stabilized zirconium beads) till required particle size was reached. Then the first milling beads were removed from the grinding chamber and second milling beads (Yttrium stabilized zirconium beads) were introduced.
  • the suspension was milled aseptically in the grinding chamber using second milling beads till required particle size was reached.
  • the suspension was filtered aseptically through a 40 micron filter into a sterilized SS container.
  • Unmicronized Paliperidone palmitate (sterile grade) was dispersed into the polysorbate solution.
  • the suspension was milled aseptically in the grinding chamber using first milling beads (Yttrium stabilized zirconium beads) till required particle size was reached.
  • first milling beads Yttrium stabilized zirconium beads
  • second milling beads Yttrium stabilized zirconium beads
  • the suspension was milled aseptically in the grinding chamber using second milling beads till required particle size was reached.
  • the suspension was filtered aseptically through a 40 micron filter into a sterilized SS container.
  • ethylenediaminetetraacetic acid EDTA
  • disodium hydrogen phosphate anhydrous sodium dihydrogen phosphate monohydrate, sodium hydroxide, polyethylene glycol 4000 were added and mixed until dissolved.
  • This solution was sterilized by filtration through sterile 0.22 micron filter and transferred aseptically into milled suspension. The final suspension was mixed until homogeneous. The suspension was filled aseptically into sterile syringes.
  • Particle Size Data The results for processing time and particle size as obtained are mentioned in table 7. All batches were having batch size of 160 ml.

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Abstract

L'invention concerne un procédé de broyage humide aseptique pour préparer une composition pharmaceutique comprenant du palmitate de palipéridone micronisé en utilisant deux types de billes de broyage. En particulier, le procédé de broyage humide aseptique utilise deux types de billes de broyage successivement dans un seul équipement pour obtenir des particules de palmitate de palipéridone micronisé dans des plages de tailles souhaitées et présentant une distribution de tailles uniforme.
PCT/IB2016/051734 2015-03-31 2016-03-26 Procédé de broyage humide aseptique pour le palmitate de palipéridone WO2016157061A1 (fr)

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Application Number Priority Date Filing Date Title
IN1299MU2015 2015-03-31
IN1300MU2015 2015-03-31
IN1299/MUM/2015 2015-03-31
IN1300/MUM/2015 2015-03-31

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190183896A1 (en) * 2017-12-14 2019-06-20 SpecGx LLC One step milling process for preparing micronized paliperidone esters
CN110279659A (zh) * 2019-07-08 2019-09-27 华裕(无锡)制药有限公司 棕榈酸帕利哌酮制剂及其制备方法
GR1009869B (el) * 2019-07-12 2020-11-12 Φαρματεν Α.Β.Ε.Ε. Ενεσιμο παρατεταμενης αποδεσμευσης φαρμακευτικο σκευασμα που περιλαμβανει παλμιτικη παλιπεριδονη και μεθοδος παρασκευης αυτου
US11304951B1 (en) 2020-11-30 2022-04-19 Janssen Pharmaceutica Nv Dosing regimens associated with extended release paliperidone injectable formulations
US11324751B1 (en) 2020-11-30 2022-05-10 Janssen Pharmaceutica Nv Dosing regimens associated with extended release paliperidone injectable formulations
WO2022111860A1 (fr) * 2020-11-30 2022-06-02 Janssen Pharmaceutica Nv Schémas posologiques associés à des formulations injectables de palipéridone à libération prolongée

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Cited By (17)

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Publication number Priority date Publication date Assignee Title
US20190183896A1 (en) * 2017-12-14 2019-06-20 SpecGx LLC One step milling process for preparing micronized paliperidone esters
WO2019118722A1 (fr) * 2017-12-14 2019-06-20 SpecGx LLC Procédé de broyage en une étape pour préparer des esters de palipéridone micronisés
JP2021506757A (ja) * 2017-12-14 2021-02-22 スペックジーエックス エルエルシー 微粉化パリペリドンエステルを調製するための一工程粉砕法
AU2018383636B2 (en) * 2017-12-14 2024-01-18 SpecGx LLC One step milling process for preparing micronized paliperidone esters
CN110279659A (zh) * 2019-07-08 2019-09-27 华裕(无锡)制药有限公司 棕榈酸帕利哌酮制剂及其制备方法
GR1009869B (el) * 2019-07-12 2020-11-12 Φαρματεν Α.Β.Ε.Ε. Ενεσιμο παρατεταμενης αποδεσμευσης φαρμακευτικο σκευασμα που περιλαμβανει παλμιτικη παλιπεριδονη και μεθοδος παρασκευης αυτου
WO2022111858A1 (fr) * 2020-11-30 2022-06-02 Janssen Pharmaceutica Nv Schémas posologiques associés à des formulations injectables de palipéridone à libération prolongée
WO2022111860A1 (fr) * 2020-11-30 2022-06-02 Janssen Pharmaceutica Nv Schémas posologiques associés à des formulations injectables de palipéridone à libération prolongée
US11324751B1 (en) 2020-11-30 2022-05-10 Janssen Pharmaceutica Nv Dosing regimens associated with extended release paliperidone injectable formulations
WO2022111859A1 (fr) * 2020-11-30 2022-06-02 Janssen Pharmaceutica Nv Schémas posologiques associés à des formulations injectables de palipéridone à libération prolongée
US11439647B2 (en) 2020-11-30 2022-09-13 Janssen Pharmaceutica Nv Dosing regimens associated with extended release paliperidone injectable formulations
US11304951B1 (en) 2020-11-30 2022-04-19 Janssen Pharmaceutica Nv Dosing regimens associated with extended release paliperidone injectable formulations
AU2021387679B2 (en) * 2020-11-30 2024-01-18 Janssen Pharmaceutica Nv Dosing regimens associated with extended release paliperidone injectable formulations
AU2021386450B2 (en) * 2020-11-30 2024-03-21 Janssen Pharmaceutica Nv Dosing regimens associated with extended release paliperidone injectable formulations
EP4356966A3 (fr) * 2020-11-30 2024-07-17 JANSSEN Pharmaceutica NV Schémas posologiques associés à des formulations injectables de palipéridone à libération prolongée
US12053474B2 (en) 2020-11-30 2024-08-06 Janssen Pharmaceutica Nv Dosing regimens associated with extended release paliperidone injectable formulations
EP4385564A3 (fr) * 2020-11-30 2024-10-09 JANSSEN Pharmaceutica NV Schémas posologiques associés à des formulations injectables de palipéridone à libération prolongée

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