WO2013115746A1 - Procédé de préparation de compositions pharmaceutiques (effervescentes) contenant un inhibiteur de l'apha-glucosidase (miglitol) et de la metformine - Google Patents

Procédé de préparation de compositions pharmaceutiques (effervescentes) contenant un inhibiteur de l'apha-glucosidase (miglitol) et de la metformine Download PDF

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Publication number
WO2013115746A1
WO2013115746A1 PCT/TR2013/000055 TR2013000055W WO2013115746A1 WO 2013115746 A1 WO2013115746 A1 WO 2013115746A1 TR 2013000055 W TR2013000055 W TR 2013000055W WO 2013115746 A1 WO2013115746 A1 WO 2013115746A1
Authority
WO
WIPO (PCT)
Prior art keywords
production method
formulation
miglitol
metformin
effervescent
Prior art date
Application number
PCT/TR2013/000055
Other languages
English (en)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
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 Mahmut Bilgic filed Critical Mahmut Bilgic
Publication of WO2013115746A1 publication Critical patent/WO2013115746A1/fr

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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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K31/13—Amines
    • A61K31/133—Amines having hydroxy groups, e.g. sphingosine
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent

Definitions

  • the present invention relates to a process used in production of the effervescent formulations comprising an alpha-glucosidase inhibitor and metformin as the active agent that shall be used in improving glycemic control in adults suffering from non-insulin dependent diabetes (type 2) wherein hyperglycaemia cannot be controlled by diet or exercise.
  • Alpha-glucosidase inhibitors are a group of active agents which affect blood sugar level positively by preventing the digestion of carbohydrates and therefore production of monosaccharides which are absorbed through the intestine.
  • the active agents belonging to said group are principally voglibose, acarbose and miglitol.
  • Voglibose (Basen®) is in 0.2 and 0.3 mg tablet dosage forms on the market. As for Miglitol (Glyset®) and acarbose (PRECOSE®), they are in 25, 50 and 100 mg tablet dosage form on the market.
  • Tablet dosage form frequently used in the prior art has disadvantages for pediatric and geriatric patients and for those who have swallowing difficulties and therefore alternative dosage forms are needed.
  • suspension forms are not mostly preferred for the reasons that they carry the possibility of uncontrolled dose intake, their production costs are high, they have physical and chemical instability problems, they cause problem during use and carrying phases.
  • suspension forms have higher bioavailability values as compared to solid dosage forms, it is seen that they are more inconvenient than solid dosage forms when viewed in terms of stability and shelf-life.
  • Effervescent dosage forms can overcome the problems encountered in solid dosage forms in the prior art.
  • Effervescent formulations comprise high amount of effervescent acid and effervescent base in order to obtain sufficient dispersion in water. This situation considerably increases unit dosage weight.
  • this type of formulations having high unit dosage weight is compressed in tablet form, various problems are encountered.
  • said effervescent tablet dosage forms are obtained by dry methods such as dry blending or dry granulation, the formulations cannot be formed into dosage forms which have desired hardness value after tablet compression and this poses problems for the manufacturers during packaging and carrying.
  • the wet granulation method that can be used as an alternative to dry methods in production of the effervescent formulations may cause undesirable results since it causes the effervescent acid and effervescent base to react during production. This results in obtainment of pretty large granules, failure to dry the granules efficiently and problems in stability of the product obtained due to the reaction.
  • the present invention relates to a method for production of effervescent formulations comprising miglitol and metformin as the active agent.
  • a characteristic feature of the method preferred for production of the effervescent formulations of the present invention is that metformin is subjected to granulation process in said production method.
  • Another characteristic feature of the method preferred for production of the effervescent formulations of the present invention is that metformin is granulated separately from the excipients comprised in the formulation in said production method.
  • the effervescent tablets with sufficient tablet hardness and the formulations having superior stability characteristics are obtained by producing metformin by wet granulation method and by preventing the contact of the active agent with the other substances comprised in the formulations during production.
  • the present invention relates to a method that shall be used in production of the effervescent formulations comprising miglitol and metfomin as the active agent, characterized in that said method is composed of the following steps:
  • the production method of the present invention is composed of the following steps:
  • the granulation solvent in the granulation solution prepared in the I st and V th steps of the production method water, ethanol, methanol, acetone, ethyl acetate, hexane, heptane, n-octane, n-butyl acetate, propanol, t-butyl alcohol, dichloromethane or aqueous HCI solution, aqueous NaOH solution or a combination thereof can be used.
  • water is used as the granulation solvent.
  • At least one pharmaceutically acceptable excipient that can be used in the V th and VIII th steps of the production method can be selected from a group comprising binder, lubricant, sweetener, flavouring agent.
  • At least one pharmaceutically acceptable excipient that shall be used in the I st and II nd steps of the production method is preferably binder.
  • the binders that shall be used in these two steps can be identical or different binders.
  • Metformin used in the effervescent formulations produced by the production method of the present invention is in the form of a pharmaceutically acceptable salt thereof, preferably in the form of metformin hydrochloride.
  • the effervescent formulations produced by the production method of the present invention comprise miglitol in the range of 1% to 80%, preferably in the range of 1% to 70%, more preferably in the range of 1% to 50% in proportion to unit dosage weight and metformin in the range of 1% to 80%, preferably in the range of 1% to 70%, more preferably in the range of 1% to 50% in proportion to unit dosage weight.
  • the ratio of miglitol to metformin used as the active agent in the effervescent formulations produced by the production method of the present invention is in the range of 0.01-8 by weight, preferably in the range of 0.03-5 by weight, more preferably in the range of 0.05-1 by weight.
  • the present invention relates to a production method for the effervescent formulations which dissolve or disperse in water or a similar solvent in less than 10 minutes, preferably in the range of 1 to 8 minutes, more preferably in the range of 1 to 5, for instance in the range of 1.5, 2, 2.5, 3 to 3.5, 4, 4.5 minutes and which comprise miglitol and metformin as the active agent.
  • the effervescent acid that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising organic acids such as malic acid, citric acid, tartaric acid, fumaric acid; the effervescent base can be selected from a group comprising agents such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate or combinations thereof.
  • the lubricant that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, sodium benzoate, potassium benzoate, sodium lauryl sulphate, talc, stearic acid, zinc stearate or combinations thereof.
  • the binder that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, maltodextrin, methyl cellulose, povidone, starch or combinations thereof.
  • the sweetener and/or taste-regulating agent that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising acesulphame, aspartame, dextrose, fructose, maltitol, maltose, mannitol, saccharin, saccharin sodium, sodium cyclamate, sorbitol, sucralose, sucrose, xylitol, sodium chloride or combinations thereof.
  • the flavouring agent that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from menthol, lemon, orange, vanilla, strawberry, raspberry, caramel and similar flavours or combinations thereof.
  • Another characteristic feature of the formulations produced by the production method of the present invention is that said formulations comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 3 kP to 50 kP.
  • formulations produced by the production method of the present invention comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 4 kP to 40 kP.
  • formulations produced by the production method of the present invention comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 5 kP to 30 kP.
  • EXAMPLE 1 Effervescent formulation comprising the combination of miglitol and metformin and production method
  • the first granulation The granulation solution comprising the granulation solvent and the binder is prepared.
  • the mixture obtained by mixing the effervescent acid, the effervescent base and the binder is granulated with the granulation solution; the granules are dried and sieved.
  • the second granulation The granulation solution comprising the granulation solvent and the sweetener is prepared. Metformin is granulated with this granulation solution. The granules are dried and sieved.
  • the granules obtained by the first and the second granulation processes are mixed with miglitol, the lubricant and the flavouring agent and compressed in tablet dosage form.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention porte sur un procédé utilisé pour la préparation de formulations effervescentes qui contiennent en tant que principe actif l'inhibiteur de l'alpha-glucosidase miglitol et de la metformine, et qui sont destinées à être utilisées pour améliorer la régulation de la glycémie chez les adultes souffrant de diabète non insulinodépendant (type 2), lorsque l'hyperglycémie ne peut être régulée par un régime alimentaire ou l'exercice physique.
PCT/TR2013/000055 2012-01-31 2013-01-31 Procédé de préparation de compositions pharmaceutiques (effervescentes) contenant un inhibiteur de l'apha-glucosidase (miglitol) et de la metformine WO2013115746A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
TR2012/01094 2012-01-31
TR201201094 2012-01-31
TR2012/03399 2012-03-26
TR201203399 2012-03-26

Publications (1)

Publication Number Publication Date
WO2013115746A1 true WO2013115746A1 (fr) 2013-08-08

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Family Applications (2)

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PCT/TR2013/000053 WO2013115744A1 (fr) 2012-01-31 2013-01-31 Procédé de préparation de compositions pharmaceutiques (effervescentes) contenant un inhibiteur de l'apha-glucosidase (p. ex. voglibose et metformine)
PCT/TR2013/000055 WO2013115746A1 (fr) 2012-01-31 2013-01-31 Procédé de préparation de compositions pharmaceutiques (effervescentes) contenant un inhibiteur de l'apha-glucosidase (miglitol) et de la metformine

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PCT/TR2013/000053 WO2013115744A1 (fr) 2012-01-31 2013-01-31 Procédé de préparation de compositions pharmaceutiques (effervescentes) contenant un inhibiteur de l'apha-glucosidase (p. ex. voglibose et metformine)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114041549A (zh) * 2021-11-29 2022-02-15 青岛博恩高科生物技术有限公司 一种电解质泡腾粉的制备方法及电解质泡腾粉

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103724248B (zh) * 2014-01-16 2018-07-27 万全万特制药江苏有限公司 维格列汀工艺杂质的制备方法
WO2016001843A1 (fr) * 2014-06-30 2016-01-07 Sun Pharmaceutical Industries Limited Comprimés de voglibose à rétention gastrique et à libération prolongée
TR201910633A1 (tr) * 2019-07-17 2021-05-21 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Si̇taglipti̇n i̇çeren efervesan tablet kompozi̇syonu
CN112220768A (zh) * 2020-10-15 2021-01-15 四川维奥制药有限公司 一种米格列醇片剂的制备方法

Citations (7)

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EP0396972A2 (fr) * 1989-05-09 1990-11-14 Bayer Ag Solution aqueuse de granulation et procédé pour la granulation de comprimés
WO1993000886A1 (fr) * 1991-07-01 1993-01-21 Gerhard Gergely Systemes effervescents dopes avec des reactifs
US5792473A (en) * 1994-03-01 1998-08-11 Gerhard Gergely Granular product or tablet containing an effervescent system and an active pharmaceutical substance, as well as a method for its preparation
EP0976395A1 (fr) * 1998-07-30 2000-02-02 Lipha Comprimé à libération prolongée d'un médicament dans l'estomac
CN101121004B (zh) * 2006-08-08 2010-07-21 鲁南制药集团股份有限公司 含有胰岛素增敏剂和米格列醇的药物组合物
CN101584688B (zh) * 2008-05-24 2010-11-10 鲁南制药集团股份有限公司 一种治疗糖尿病及其并发症的药物组合物
WO2011093823A2 (fr) * 2010-01-29 2011-08-04 Mahmut Bilgic Formulations effervescentes comprenant du céfaclor et de l'acide clavulanique

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TW580397B (en) * 1997-05-27 2004-03-21 Takeda Chemical Industries Ltd Solid preparation
EP1367999A4 (fr) * 2001-02-16 2007-04-18 Lavipharm Lab Inc Complexes hydrosolubles et palatables
KR100822519B1 (ko) * 2005-02-15 2008-04-16 주식회사종근당 위장 내에서 제어방출되는 단일 매트릭스 정제
TR201100150A2 (tr) * 2011-01-06 2012-07-23 Bi̇lgi̇ç Mahmut Suda çözünür dozaj formları

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0396972A2 (fr) * 1989-05-09 1990-11-14 Bayer Ag Solution aqueuse de granulation et procédé pour la granulation de comprimés
WO1993000886A1 (fr) * 1991-07-01 1993-01-21 Gerhard Gergely Systemes effervescents dopes avec des reactifs
US5792473A (en) * 1994-03-01 1998-08-11 Gerhard Gergely Granular product or tablet containing an effervescent system and an active pharmaceutical substance, as well as a method for its preparation
EP0976395A1 (fr) * 1998-07-30 2000-02-02 Lipha Comprimé à libération prolongée d'un médicament dans l'estomac
CN101121004B (zh) * 2006-08-08 2010-07-21 鲁南制药集团股份有限公司 含有胰岛素增敏剂和米格列醇的药物组合物
CN101584688B (zh) * 2008-05-24 2010-11-10 鲁南制药集团股份有限公司 一种治疗糖尿病及其并发症的药物组合物
WO2011093823A2 (fr) * 2010-01-29 2011-08-04 Mahmut Bilgic Formulations effervescentes comprenant du céfaclor et de l'acide clavulanique

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Title
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; October 2001 (2001-10-01), VAN GAAL L ET AL: "Miglitol combined with metformin improves glycaemic control in type 2 diabetes.", XP002697694, Database accession no. NLM11703422 *
DIABETES, OBESITY & METABOLISM OCT 2001, vol. 3, no. 5, October 2001 (2001-10-01), pages 326 - 331, ISSN: 1462-8902 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114041549A (zh) * 2021-11-29 2022-02-15 青岛博恩高科生物技术有限公司 一种电解质泡腾粉的制备方法及电解质泡腾粉
CN114041549B (zh) * 2021-11-29 2024-02-20 青岛博恩高科生物技术有限公司 一种电解质泡腾粉的制备方法及电解质泡腾粉

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