EP2571484A2 - Formulations effervescentes - Google Patents

Formulations effervescentes

Info

Publication number
EP2571484A2
EP2571484A2 EP11740739A EP11740739A EP2571484A2 EP 2571484 A2 EP2571484 A2 EP 2571484A2 EP 11740739 A EP11740739 A EP 11740739A EP 11740739 A EP11740739 A EP 11740739A EP 2571484 A2 EP2571484 A2 EP 2571484A2
Authority
EP
European Patent Office
Prior art keywords
effervescent
pharmaceutically acceptable
formulation
sorbitol
maltodextrin
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.)
Withdrawn
Application number
EP11740739A
Other languages
German (de)
English (en)
Inventor
Mahmut Bilgic
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP2571484A2 publication Critical patent/EP2571484A2/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent
    • 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
    • A61K31/4965—Non-condensed pyrazines
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin

Definitions

  • the present invention relates to stable levocetirizine effervescent formulations flavor and taste of which has been improved in order to be used in the treatment of seasonal allergic rhinitis, perennial allergic rhinitis, chronic idiopathic urticaria, and the methods for preparation of said formulations.
  • Levocetirizine is a non-sedating, long-acting HI anti-histaminic displayed in formula (I) below which has the chemical name 2-[4-[(i?)-(4-chlorophenyl)-phenyl-methyl]piperazin- l-yl]ethoxy] acetic acid (Formula I).
  • Cetirizine was first disclosed in the patent numbered EP0058146 Al.
  • Levocetirizine which is an R-enantiomer of cetirizine is a piperazine derivative, potent and selective HI receptor antagonist.
  • Levocetirizine is a new anti-histaminic that binds to HI receptors with high affinity, even twelve times higher than cetirizine.
  • Levocetirizine competes with histamine and prevents histamine to bind to HI receptors. This antagonism blocks the effects of histamine on gastrointestinal channel, uterus, large blood vessels and bronchial smooth muscle. Blockage of HI receptors impedes histaminic activities such as edema, warmness and itchiness.
  • the facts that levocetirizine does not enter the central nervous system in significant amounts and its affinity to HI receptors there is low can explain its non-sedating characteristics to some extent.
  • Levocetirizine has antiallergic and anti-inflammatory activity.
  • the studies conducted have presented that levocetirizine inhibits the wide range of chain of events starting and spreading out the allergic inflammation.
  • Levocetinzine formulations existing in the prior art are in oral solution, oral drop and film tablet form.
  • solid dosage forms such as tablets have lower bioavailability than solution forms and they generally pose difficulty of use for geriatric, pediatric and physically handicapped patients who have swallowing difficulties.
  • Oral solution and suspension forms produced as an alternative to these forms, on the other hand are not preferable much as the stability of active agents cannot be maintained for long in these forms and they have short shelf life.
  • Another disadvantage of these forms is that they have a risk of high and/or uncontrolled dose intake in pediatric and geriatric patients.
  • dosage forms Another alternative in terms of dosage forms is effervescent forms which satisfy the expectations of bioavailability, shelf life, ease of use and carrying and accurate dosing.
  • Effervescent forms are more advantageous than conventional forms owing to fast dispersion.
  • Effervescent formulations disperse fast; emit the component/components simultaneously and rapidly into aqueous liquid.
  • the time which passes between adding the formulation into water and swallowing the solution is relatively short. Consumption of the formulations in a short time prevents the degradation of the active agent with water and thus, this type of formulations that are consumed in a short time do not require high amounts of stabilizing agent.
  • levocetirizine formulations Another significant problem about levocetirizine formulations is that it is hard to formulate them due to the bitter taste of the active agent and its difficulty of use by patients.
  • various pharmaceutical excipients such as sweeteners, flavoring agents or aroma in formulations of levocetirizine. Most often, use of sweeteners only is not enough to mask the bitter taste in the formulations.
  • some other excipients are used in addition to sweeteners.
  • the most frequently used excipients for this purpose are sugar alcohols such as mannitol, sorbitol; sugars such as sucrose, fructose; polyols such as cyclodextrins.
  • the present invention relates to user-friendly levocetirizine formulations having high bioavailability bitter taste of which are masked and which can be produced without conducing to undesirable by-products, and the production method of said formulations.
  • the inventors have surprisingly masked the bitter taste by using at least one polyol and/or derivative thereof in the formulations and managed to produce stable formulations of levocetirizine.
  • the formulations of the present invention are characterized in being in effervescent form.
  • a characteristic feature of formulations of the present invention is that polyol derivative excipients can be included in the formulations of the present invention without conducing to any stability problem resulting from their interaction with cetirizine derivatives.
  • polyol derivative excipients utilized in the formulations of the present invention for different purposes such as bulking agent is also known in the prior art in addition to their sweetening and/or taste masking functions.
  • Polyol derivatives used in the formulations of the present invention can fulfill one or more functions at the same time.
  • the formulations of the present invention comprise levocetirizine or pharmaceutically acceptable salt, ester, solvate, derivative, polymorph or hydrate thereof as the active agent.
  • the formulations of the present invention are used in the treatment of allergic rhinitis (including seasonal allergic rhinitis comprising ocular symptoms), persistent allergic rhinitis, perennial allergic rhinitis and chronic idiopathic urticaria.
  • the purpose of the present invention is to produce an effervescent tablet which provides ease of administration by the oral route in aqueous solution form.
  • the formulation rapidly disperses in the aqueous liquid and it can be administered by the oral route, by spoon or dropper where necessary. This type of formulations are more advantageous for use especially in physically handicapped and elderly patients.
  • the formulations of the present invention comprise the following constituents:
  • Active agent in an amount in the range of 0.1 % to 80% by weight
  • At least one effervescent couple in an amount in the range of 60% to 90% by weight
  • At least one pharmaceutically acceptable polyol and/or derivative thereof in an amount in the range of 1 % to 30% by weight
  • At least one pharmaceutically acceptable sweetener in an amount in the range of 5% to 30% by weight
  • At least one pharmaceutically acceptable flavoring agent in an amount in the range of l% to 10% by weight
  • At least one pharmaceutically acceptable solvent in an amount in the range of 5% to 20% by weight
  • the pharmaceutical formulations of the present invention comprise other pharmaceutically acceptable additives and excipients selected from a group comprising disintegrants, viscosity enhancers, filling materials, drying agents, lubricants, diluents, binders, glidants, anti-foam agents, wetting agents, effervescent mixtures, sweeteners and flavoring agents.
  • the effervescent bases which can be used in the formulations of the present invention comprise sodium, potassium and calcium carbonates, bicarbonates and/or sodium glycine carbonate or a combination thereof.
  • the effervescent couple used in the formulations of the present invention is preferably composed of hydrogen carbonate and citric acid.
  • the disintegrant which can be used in the present invention can be selected from polymers having high disintegrating characteristics such as cross-linked hydroxypropyl cellulose, polyvinylpyrrolidone, high molecular weight polymers, microcrystalline cellulose, sodium starch glycolate, povidone, the products known as Crospovidone®, Polyplasdone® or Kollidon® XL, alginic acid, sodium alginate.
  • polymers having high disintegrating characteristics such as cross-linked hydroxypropyl cellulose, polyvinylpyrrolidone, high molecular weight polymers, microcrystalline cellulose, sodium starch glycolate, povidone, the products known as Crospovidone®, Polyplasdone® or Kollidon® XL, alginic acid, sodium alginate.
  • the filling materials which can be used in the formulations of the present invention can be selected from a group comprising talc, calcium carbonate, microcrystalline cellulose, powderized cellulose, dextrates, kaolin, mannitol, silicic acid, sorbitol, starch, pregelatinized starch, maltodextrin or a combination thereof.
  • Polyol derivative excipients used in the granulation solution are preferably sorbitol and maltodextrin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention porte sur des formulations effervescentes stables de lévocétirizine, dont l'arôme et le goût sont améliorés, et sur un procédé pour la préparation desdites formulations.
EP11740739A 2010-05-18 2011-05-16 Formulations effervescentes Withdrawn EP2571484A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR201003940 2010-05-18
PCT/TR2011/000112 WO2011146032A2 (fr) 2010-05-18 2011-05-16 Formulations effervescentes

Publications (1)

Publication Number Publication Date
EP2571484A2 true EP2571484A2 (fr) 2013-03-27

Family

ID=44484008

Family Applications (1)

Application Number Title Priority Date Filing Date
EP11740739A Withdrawn EP2571484A2 (fr) 2010-05-18 2011-05-16 Formulations effervescentes

Country Status (2)

Country Link
EP (1) EP2571484A2 (fr)
WO (1) WO2011146032A2 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013058721A1 (fr) * 2011-10-13 2013-04-25 Mahmut Bilgic Granulés pharmaceutiques et leur procédé de production
WO2016140630A1 (fr) 2015-03-05 2016-09-09 PHARMACTIVE ILAÇ SANAYI VE TlCARET A. Ş. Composition effervescente comprenant de la lévocétirizine et de la pseudoéphédrine
US20230414597A1 (en) 2020-11-18 2023-12-28 BioPharma Synergies, S. L. Orodispersible powder composition comprising an antihistamine compound

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NO155805C (no) 1981-02-06 1987-06-10 Ucb Sa Analogifremgangsmaate for fremstilling av terapeutisk virksomme 2-(4-(difenylmethyl)-1-piperazinyl)-eddiksyrer og deres amider og ikke-toksiske salter.
EP0811375B1 (fr) 1995-02-21 2001-01-03 Nippon Suisan Kaisha, Ltd. Agoniste de recepteur d'acide glutamique
DE19814256A1 (de) * 1998-03-31 1999-10-07 Asta Medica Ag Feste, schnellzerfallende Cetirizin-Formulierungen
EP1467715B1 (fr) * 2002-01-15 2010-11-03 Ucb Farchim S.A. Formulations pour l'adminstration orale de composes actifs
US20060083786A1 (en) * 2004-07-29 2006-04-20 Glenmark Pharmaceuticals Limited Taste masking pharmaceutical composition containing levocetirizine
US20060127479A1 (en) * 2004-10-08 2006-06-15 Natrajan Kumaraperumal Solvent free taste masked pharmaceutical compositions
US20090269393A1 (en) * 2006-06-12 2009-10-29 Jubliant Organosys Limited Chewable Bilayer Tablet Formulation
AU2009288006B2 (en) * 2008-09-05 2014-07-17 Mcneil-Ppc, Inc. Method for making cetirizine tablets

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2011146032A2 *

Also Published As

Publication number Publication date
WO2011146032A3 (fr) 2012-03-08
WO2011146032A2 (fr) 2011-11-24

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