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
  • A61K9/0012—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
  • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
  • A61K31/4164—1,3-Diazoles
  • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• • 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
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
  • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
  • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• • 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
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
  • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
  • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
  • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
  • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
  • A61L2/0029—Radiation
  • A61L2/0035—Gamma radiation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• Proton pump inhibitors are sensitive to heat and light and susceptible to chemical degradation in liquid solutions.
• the chemical degradation is pH-dependent and the rate of reaction is very high at low pH values.
• Formulations for parenteral administration comprising proton pump inhibitor compounds are due to their chemical susceptibility formulated as solid formulations for ex tempore reconstitution in a sterile solvent just before use. These solid formulations have so far been obtained by lyophilisation of a sterile filtered and aseptically filled solution. Lyophilisation is a process where the material (in this case the solution) is freeze-dried in a vacuum to vaporize the frozen water. The resulting product is a porous cake or powder. Lyophilisation is a complex and time consuming process, and hence very expensive. The chemical instability of the proton pump inhibitors precludes heat sterilization of this class of compounds. These compounds must also be protected from light because of their light sensitivity.
• WO 94/02141 describes an injection of an antiulcerative benzimidazole compound, such as omeprazole.
• the injection comprises a lyophilized product, which is dissolved in physiological saline just before use.
• the lyophilized product is prepared from the sodium salt of omeprazole together with sodium hydroxide using water as the solvent.
• the present invention provides stable solid formulations suitable for parenteral administration after ex tempore reconstitution in a sterile solvent, without using any lyophilisation processes/steps in the manufacturing process of the formulation. It has surprisingly been found that it is possible to sterilize by ionizing radiation a solid formulation comprising an acid susceptible proton pump inhibitor compound, which is sensitive to light exposure.
• the invention also relates to an ex tempore prepared solution of the sterilized stable solid formulation comprising an acid susceptible proton pump inhibitor and optionally pharmaceutically acceptable excipients.
• a solution for parenteral administration is prepared by mixing the sterilized stable solid formulation with a suitable sterile solvent.
• Alkyl groups, alkoxy groups and moieties thereof in the definitions above may be branched or straight d-C 9 -chams or comprise cyclic alkyl groups, such as cycloalkylalkyl;
• the compound of formula (I) or a separate single enantiomer thereof is incorporated in the form of a pharmaceutically acceptable salt in the claimed sterilized parenteral formulation and sterilized solid formulation.
• the solid formulation is non-lyophilized and it is filled in its final container before it is sterilized by radiation.
• the sterilized formulation is suitable for an ex tempore preparation of a solution for parenteral administration.
• Suitable final containers for the present invention are multi-compartment systems, such as two-chamber infusion bags and two-compartment syringes. These containers may also be provided with a particle filter, i.e. that the solution for parenteral administration is filtered in the device before administered to the body.
• the magnitude of the therapeutic dose will depend on the nature and severity of the disease to be treated.
• the dose, and dose frequency may also vary according to the age, body weight and response of the individual patient. Special requirements may be needed for patients having Zollinger-Ellison syndrome, or Peptic 0 Ulcer Bleed such as a need for higher doses than the average patient. Children and patients with liver diseases generally will benefit from doses that are somewhat lower than the average. Thus, in some conditions it may be necessary to use doses outside the ranges stated below, for example long-term treatments may request lower dosage. Such higher and lower doses are within the scope of the present invention.
• Daily doses may vary between 5 5 mg to 300 mg. Suitable doses for injection and infusion comprise for instance 5, 10, 15, 20, 30, 40, 60, 80 and 100 mg of the pharmaceutical active compound.
• the present invention also relates to the use of the formulation as disclosed above in the manufacture of a medicament to be used in the treatment of gastrointestinal diseases.
• the spray- dried formulations were obtained by first dissolving the dry esomeprazole sodium powder (either with or without excipient) in water and then drying the formulation in a lab-scale spray-dryer using co-current flow and a two-fluid nozzle.
• the inlet temperature was about 170 0 C and the outlet temperature about 80 - 90 0 C.

Priority Applications (9)

Applications Claiming Priority (2)

Publications (1)

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Cited By (4)

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Citations (4)

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• 2007
  • 2007-05-07 AU AU2007248949A patent/AU2007248949B2/en not_active Ceased
  • 2007-05-07 US US12/299,684 patent/US20090111856A1/en not_active Abandoned
  • 2007-05-07 EP EP07748104A patent/EP2018151A4/en not_active Withdrawn
  • 2007-05-07 CN CNA2007800168871A patent/CN101442985A/zh active Pending
  • 2007-05-07 MX MX2008014283A patent/MX2008014283A/es not_active Application Discontinuation
  • 2007-05-07 NZ NZ572007A patent/NZ572007A/en not_active IP Right Cessation
  • 2007-05-07 JP JP2009509484A patent/JP2009536195A/ja active Pending
  • 2007-05-07 KR KR1020087027385A patent/KR20090024674A/ko not_active Application Discontinuation
  • 2007-05-07 BR BRPI0711048-0A patent/BRPI0711048A2/pt not_active IP Right Cessation
  • 2007-05-07 WO PCT/SE2007/000440 patent/WO2007129961A1/en active Application Filing
  • 2007-05-07 CA CA002649946A patent/CA2649946A1/en not_active Abandoned
• 2008
  • 2008-10-15 ZA ZA200808824A patent/ZA200808824B/xx unknown
  • 2008-11-21 NO NO20084914A patent/NO20084914L/no not_active Application Discontinuation

Patent Citations (4)

Non-Patent Citations (2)

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