RU2009149675A - STABLE MEDICINAL FORM OF PERINDOPRIL AMORPHIC SALTS, METHOD FOR ITS PRODUCTION IN INDUSTRIAL SCALES AND APPLICATION FOR TREATMENT OF HYPERTENSION - Google Patents

STABLE MEDICINAL FORM OF PERINDOPRIL AMORPHIC SALTS, METHOD FOR ITS PRODUCTION IN INDUSTRIAL SCALES AND APPLICATION FOR TREATMENT OF HYPERTENSION Download PDF

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RU2009149675A
RU2009149675A RU2009149675/15A RU2009149675A RU2009149675A RU 2009149675 A RU2009149675 A RU 2009149675A RU 2009149675/15 A RU2009149675/15 A RU 2009149675/15A RU 2009149675 A RU2009149675 A RU 2009149675A RU 2009149675 A RU2009149675 A RU 2009149675A
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alkaline earth
perindopril
alkali
earth metal
substances
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RU2009149675/15A
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RU2464022C2 (en
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Рудольф РУЧМАН (SI)
Рудольф РУЧМАН
Павел ЖУПЕТ (SI)
Павел Жупет
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Силверстоун Фарма (Li)
Силверстоун Фарма
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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
    • A61K9/14—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
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • 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
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
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  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

1. Способ получения стабильной лекарственной формы аморфной соли периндоприла по формуле 1: ! ! где B+ представляет собой катион щелочного или щелочноземельного металла, отличающийся тем, что периндоприл в форме свободной кислоты формулы III: ! ! растворяют в спирте и нейтрализуют водным раствором щелочного или щелочноземельного основания и полученный нейтральный раствор соли распыляют на гомогенную смесь инертных ингредиентов для получения гранулята, который сушат в вакууме или потоке теплого воздуха, добавляют вещества для облегчения таблетирования или другие активные вещества, предпочтительно диуретики, и затем гомогенизируют и таблетируют. ! 2. Способ по п.1, отличающийся тем, что используется свободная кислота формулы III в форме масла, смолистого вещества, кристаллов, водных растворов или растворов в водосодержащих смесях. ! 3. Способ по п.1, отличающийся тем, что щелочноземельный металл представляет собой кальций или магний и щелочной металл представляет собой натрий или калий, предпочтительно натрий. ! 4. Способ по п.1, отличающийся тем, что в качестве основания используется гидроксид, оксид, карбонат или гидрокарбонат щелочного или щелочноземельного металла. ! 5. Способ по п.1, отличающийся тем, что сушка проводится при температуре от 30 до 50°С. ! 6. Способ по п.1, отличающийся тем, что вещества, обладающие диуретической активностью, предпочтительно индапамид, в качестве другого активного вещества, на последней фазе гранулирования подмешиваются к смеси. ! 7. Применение стабильной лекарственной формы, полученной в соответствии с пп. 1-6 в качестве лекарственного средства, обладающего антигипертонической и сос� 1. The method of obtaining a stable dosage form of the amorphous salt of perindopril according to the formula 1:! ! where B + is an alkali or alkaline earth metal cation, characterized in that perindopril in the form of a free acid of formula III:! ! dissolved in alcohol and neutralized with an aqueous solution of an alkaline or alkaline earth base and the resulting neutral salt solution is sprayed onto a homogeneous mixture of inert ingredients to obtain a granulate which is dried in a vacuum or a stream of warm air, substances to facilitate tabletting or other active substances, preferably diuretics, are added, and then homogenize and tablet. ! 2. The method according to claim 1, characterized in that the free acid of the formula III is used in the form of an oil, a resinous substance, crystals, aqueous solutions or solutions in aqueous mixtures. ! 3. The method according to claim 1, characterized in that the alkaline earth metal is calcium or magnesium and the alkali metal is sodium or potassium, preferably sodium. ! 4. The method according to claim 1, characterized in that the base is a hydroxide, oxide, carbonate or hydrogen carbonate of an alkali or alkaline earth metal. ! 5. The method according to claim 1, characterized in that the drying is carried out at a temperature of from 30 to 50 ° C. ! 6. The method according to claim 1, characterized in that substances having diuretic activity, preferably indapamide, as another active substance, are mixed with the mixture in the last granulation phase. ! 7. The use of a stable dosage form obtained in accordance with paragraphs. 1-6 as a medicine with antihypertensive and

Claims (7)

1. Способ получения стабильной лекарственной формы аморфной соли периндоприла по формуле 1:1. The method of obtaining a stable dosage form of the amorphous salt of perindopril according to the formula 1:
Figure 00000001
Figure 00000001
 где B+ представляет собой катион щелочного или щелочноземельного металла, отличающийся тем, что периндоприл в форме свободной кислоты формулы III:where B + is an alkali or alkaline earth metal cation, characterized in that perindopril in the form of a free acid of formula III:
Figure 00000002
Figure 00000002
 растворяют в спирте и нейтрализуют водным раствором щелочного или щелочноземельного основания и полученный нейтральный раствор соли распыляют на гомогенную смесь инертных ингредиентов для получения гранулята, который сушат в вакууме или потоке теплого воздуха, добавляют вещества для облегчения таблетирования или другие активные вещества, предпочтительно диуретики, и затем гомогенизируют и таблетируют.dissolved in alcohol and neutralized with an aqueous solution of an alkaline or alkaline earth base and the resulting neutral salt solution is sprayed onto a homogeneous mixture of inert ingredients to obtain a granulate which is dried in a vacuum or a stream of warm air, substances to facilitate tabletting or other active substances, preferably diuretics, are added, and then homogenize and tablet. 2. Способ по п.1, отличающийся тем, что используется свободная кислота формулы III в форме масла, смолистого вещества, кристаллов, водных растворов или растворов в водосодержащих смесях.2. The method according to claim 1, characterized in that the free acid of the formula III is used in the form of an oil, a resinous substance, crystals, aqueous solutions or solutions in aqueous mixtures. 3. Способ по п.1, отличающийся тем, что щелочноземельный металл представляет собой кальций или магний и щелочной металл представляет собой натрий или калий, предпочтительно натрий.3. The method according to claim 1, characterized in that the alkaline earth metal is calcium or magnesium and the alkali metal is sodium or potassium, preferably sodium. 4. Способ по п.1, отличающийся тем, что в качестве основания используется гидроксид, оксид, карбонат или гидрокарбонат щелочного или щелочноземельного металла.4. The method according to claim 1, characterized in that the base is a hydroxide, oxide, carbonate or bicarbonate of an alkali or alkaline earth metal. 5. Способ по п.1, отличающийся тем, что сушка проводится при температуре от 30 до 50°С.5. The method according to claim 1, characterized in that the drying is carried out at a temperature of from 30 to 50 ° C. 6. Способ по п.1, отличающийся тем, что вещества, обладающие диуретической активностью, предпочтительно индапамид, в качестве другого активного вещества, на последней фазе гранулирования подмешиваются к смеси.6. The method according to claim 1, characterized in that substances having diuretic activity, preferably indapamide, as another active substance, are mixed with the mixture in the last granulation phase. 7. Применение стабильной лекарственной формы, полученной в соответствии с пп. 1-6 в качестве лекарственного средства, обладающего антигипертонической и сосудорасширяющей активностью. 7. The use of a stable dosage form obtained in accordance with paragraphs. 1-6 as a drug having antihypertensive and vasodilator activity.
RU2009149675/15A 2007-06-04 2008-05-30 Stable dosage form of amorphous perindopril salts, method for preparing it industrially and using for treating hypertension RU2464022C2 (en)

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SI200700131A SI22542A (en) 2007-06-04 2007-06-04 Stable formulation of amorphous salts of perindopril, procedure for its preparation in industrial scale and its application for treatmentof hypertensia
SIP-200700131 2007-06-04

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AU2013201812B2 (en) * 2007-06-27 2015-04-02 Les Laboratoires Servier Salts of perindopril
SI22543A (en) * 2007-06-27 2008-12-31 Krka, Tovarna Zdravil, D.D., Novo Mesto New salts of perindopril
SI23149A (en) 2009-09-21 2011-03-31 Silverstone Pharma New benzatin salts of ace inhibitors, procedure for their preparationand their application for treatment of cardiovascular diseases

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FR2838648B1 (en) * 2002-04-18 2004-05-21 Servier Lab NEW PERINDOPRIL SALT AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING IT
SI21703A (en) * 2004-01-14 2005-08-31 Lek Farmacevtska Druzba Dd Inclusion complexes of perindopril, procedure of their preparation, pharmaceutical compositions containing these complexes and their application in treatment of hypertensia
SI21704A (en) * 2004-01-14 2005-08-31 Lek Farmacevtska Druzba Dd New crystal form of perindopril, procedure of its preparation, pharmaceutical preparations containing this form and their application in treatment of hypertensia
RS53324B (en) * 2005-11-17 2014-10-31 Silverstone Pharma Est. Stable formulation of amorphous perindopril salts, a process for their preparation, especially industrial preparation, and their use in the therapy of hypertension

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CN101742986B (en) 2013-07-17
RU2464022C2 (en) 2012-10-20
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