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WO2014092661A1 - Formulations particulaires de tadalafil sous forme effervescente - Google Patents

Formulations particulaires de tadalafil sous forme effervescente Download PDF

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Publication number
WO2014092661A1
WO2014092661A1 PCT/TR2013/000035 TR2013000035W WO2014092661A1 WO 2014092661 A1 WO2014092661 A1 WO 2014092661A1 TR 2013000035 W TR2013000035 W TR 2013000035W WO 2014092661 A1 WO2014092661 A1 WO 2014092661A1
Authority
WO
WIPO (PCT)
Prior art keywords
effervescent
formulation
range
tadalafil
agent
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.)
Ceased
Application number
PCT/TR2013/000035
Other languages
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 WO2014092661A1 publication Critical patent/WO2014092661A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K9/0002—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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems

Definitions

  • the present invention relates to pharmaceutical effervescent formulations comprising tadalafil for use in the treatment of erectile dysfunction.
  • Tadalafil was first disclosed in the application numbered W09519978. Use of tadalafil for the treatment of erectile dysfunction is disclosed in said document.
  • Tadalafil is available in 5 mg, 10 mg and 20 mg tablet forms on the market.
  • Particle size of the active agent is of great importance for the effervescent tablet forms. It generally affects the granule formulation, the solubility and bioavailability of the active agent and overall the dissolution of the effervescent tablet forms.
  • dio:d 50 ratio of the active agent tadalafil is in the range of 1 : 1.1 to 1 :15 and d 50 :d 9 o ratio of the active agent tadalafil is in the range of 1 :1.1 to 1 :5, said formulations dissolve easily in water and thus high absorption and bioavailability of active agent tadalafil, and effective treatment can be provided.
  • the present invention relates to the effervescent formulations comprising tadalafil wherein di 0 :d 50 ratio of the active agent tadalafil is in the range of 1 : 1.1 to 1 : 15 and d 50 :d9 0 ratio of the active agent tadalafil is in the range of 1 :1.1 to 1 :5.
  • di 0 :d 50 ratio of the active agent tadalafil is preferably in the range of 1 :5 to 1 :10 and d 5 o:d9 0 ratio of the active agent tadalafil is preferably in the range of 1 :2 to 1 :4.
  • d 50 used herein signifies that half of the said substance by volume has a particle size below the value stated with d 50 and the other half of the substance by volume has a particle size over the value stated with d 50 .
  • di 0 used herein signifies that 10 % of the said substance by volume has a particle size below the value stated with dio and the rest of the substance has a particle size over the value stated with d] 0 .
  • d 90 used herein signifies that 90 % of the said substance by volume has a particle size below the value stated with d 90 and the rest of the substance has a particle size over the value stated with d 90 .
  • d 50 , dio, d 90 values can be measured by one of the known measuring devices, for instance with a device which measures particle distribution by laser diffraction (for instance, Malvern Mastersizer etc.).
  • effervescent formulations of the present invention comprise tadalafil in the range of 0.01-10 %, preferably in the range of 0.05-5 %, more preferably in the range of 0.1-3 % by weight of the total amount of formulation.
  • Tadalafil that is comprised in the formulations of the present invention is in the form of its pharmaceutically acceptable salts, hydrates, solvates, esters, enantiomers, diastereomers or combinations thereof in terms of chemical structure; in amorphous or crystalline form or a combination thereof in terms of polymorphic structure.
  • effervescent formulations of the present invention comprise at least one pharmaceutically acceptable excipient along with tadalafil.
  • the pharmaceutically acceptable excipients that can be used in the effervescent formulations of the present invention can be selected from a group comprising effervescent acid, effervescent base, binder, sweetener and/or taste modifying agent, flavouring agent, lubricant, coloring agent and anti-foaming agent.
  • the effervescent acid that can be used in the effervescent formulations of the present invention and comprising tadalafil can be selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid and tartaric acid or a combination thereof.
  • the effervescent base that can be used in the effervescent formulations of the present invention and comprising tadalafil can be selected from a group comprising sodium bicarbonate, sodium citrate dihydrate, sodium hydroxide or combinations thereof.
  • binders that can be used in the effervescent formulations of the present invention and comprising tadalafil can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, sorbitol, methylcellulose, povidone or a combination thereof.
  • solubility characteristics of the granules which are obtained during the preparation of the formulation. Granules having low flow characteristics may cause deviations in the tablet weight uniformity which results in unevenly distributed dose of the active agent.
  • An optimal binder composition is of a significant importance for obtaining granules with desired flow characteristics.
  • the inventors have surprisingly found that using a binder combination of two binding agents shows significant improvement in the problems known in the prior art and helps the granules to have desired flow characteristics.
  • the binder combination comprises the first binding agent and the second binding agent.
  • the first binding agent of the binder combination is preferably povidone and the second binding agent of the binder combination is preferably sorbitol.
  • the inventors have also surprisingly found that in the case that the ratio of the first binding agent to the second binding agent is between 1 :10 and 10:1, preferably between 1 :5 and 5:1, the granules having proper flow and high solubility can be provided.
  • another embodiment of the present invention is the effervescent formulation comprising tadalafil wherein said formulation comprises a binder combination comprising the first binding agent and the second binding agent and wherein the ratio of the first binding agent to the second binding is in the range of 1 :10 to 10:1, preferably 1 :5 to 5:1 by weight.
  • the sweetener and/or taste modifying agent that can be used in the effervescent formulations of the present invention can be selected from a group comprising acesulfame potassium, aspartame, fructose, maltitol, xylitol, saccharin, sodium cyclamate, sucralose, sucrose, sodium chloride.
  • the flavouring agent that can be used in the effervescent formulations of the present invention can be selected from menthol, methane, anethole, methyl salicylate, eucalyptol,' cinnamon, 1 - methyl acetate, sage, eugenol, oxanone, lemon, orange, strawberry, blackberry or combinations thereof.
  • the colouring agent that can be used in the effervescent formulations of the present invention can be selected from titanium dioxide, chlorophyl, yellow iron oxide, other synthetic iron oxides, beta-carotene or combinations thereof.
  • the lubricant that can be used in the effervescent formulations of the present invention can be selected from calcium stearate, magnesium stearate, talc, polyethylene glycol, PEG 6000, sodium benzoate, potassium benzoate, sodium lauryl sulphate, stearic acid, zinc stearate or combinations thereof.
  • the anti-foaming agent that can be used in the effervescent formulations of the present invention can be selected from polydimethylsiloxane, simethicone, other silicones, stearates, alcohols, glycols or combinations thereof.
  • the effervescent formulations of the present invention comprising tadalafil are characterized in that the amount of the active agent is in the range of 0.01-10 %, effervescent acid in the range of 1-80 %, effervescent base in the range of 1-70 %, binder in the range of 1-30 %, sweetener and/or taste modifying agent in the range of 1-30 %, lubricant in the range of 0.1-5 %, flavouring agent in the range of 0.1-10 %, colouring agent in the range of 0.01-10 %, anti- foaming agent in the range of 0.001-2 % in proportion to total weight of the formulation.
  • the method for preparation of the effervescent formulations of the present invention comprising tadalafil can be composed of the following steps: I. Tadalafil, a solvent and effervescent acid are mixed and the granulation solution is obtained.
  • flavouring agent the colouring agent, and the taste modifying agent are added into the granules obtained in the step III and the final mixture is obtained.
  • step IV The final mixture obtained in step IV is compressed into tablet form.
  • the pharmaceutical formulation according to the present invention can be used in prevention and treatment of erectile dysfunction.
  • Example 1 Formulation and process for preparation of tadalafil effervescent tablet
  • flavouring agent the colouring agent, and the taste modifying agent are added into the granules obtained in the step III and the final mixture is obtained.
  • step IV The final mixture obtained in step IV is compressed into tablet form.

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)

Abstract

L'invention concerne des formulations pharmaceutiques sous forme effervescente comprenant du tadalafil et destinées à être utilisées dans le traitement d'un dysfonctionnement érectile.
PCT/TR2013/000035 2012-01-18 2013-01-18 Formulations particulaires de tadalafil sous forme effervescente Ceased WO2014092661A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR201200601 2012-01-18
TR2012/00601 2012-01-18

Publications (1)

Publication Number Publication Date
WO2014092661A1 true WO2014092661A1 (fr) 2014-06-19

Family

ID=48083586

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/TR2013/000035 Ceased WO2014092661A1 (fr) 2012-01-18 2013-01-18 Formulations particulaires de tadalafil sous forme effervescente
PCT/TR2013/000043 Ceased WO2013109230A1 (fr) 2012-01-18 2013-01-18 Compositions pharmaceutiques contenant du tadalafil

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/TR2013/000043 Ceased WO2013109230A1 (fr) 2012-01-18 2013-01-18 Compositions pharmaceutiques contenant du tadalafil

Country Status (1)

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WO (2) WO2014092661A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014167579A2 (fr) * 2013-03-28 2014-10-16 Astron Research Limited Compositions pharmaceutiques stables de tadalafil
MX379254B (es) * 2016-02-26 2025-03-10 Apotex Inc Formulaciones farmacéuticas novedosas que comprenden un inhibidor de pde5.
WO2025004098A1 (fr) * 2023-06-25 2025-01-02 Zenvision Pharma Llp Composition pharmaceutique comprenant un peptide d'huître et un ou plusieurs inhibiteurs de pde5 ou des sels de ceux-ci

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995019978A1 (fr) 1994-01-21 1995-07-27 Laboratoires Glaxo Wellcome S.A. Derives tetracycliques, leurs procedes de preparation et leur utilisation
US6821975B1 (en) * 1999-08-03 2004-11-23 Lilly Icos Llc Beta-carboline drug products
US20060286166A1 (en) * 2005-02-25 2006-12-21 Inbal Ornan Tadalafil having a large particle size and a process for preparation thereof
US20070098804A1 (en) * 2005-08-29 2007-05-03 Judith Aronhime Solid particulate tadalafil having a bimodal particle size distribution
US20070104792A1 (en) * 2005-09-13 2007-05-10 Elan Pharma International, Limited Nanoparticulate tadalafil formulations
EP1985310A1 (fr) * 2007-04-25 2008-10-29 Teva Pharmaceutical Industries Ltd. Formes de dosage solide

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009052421A1 (fr) * 2007-10-19 2009-04-23 Innozen, Inc. Composition pour administrer un ingrédient actif et procédé de préparation et d'utilisation de cette composition
WO2011030351A2 (fr) * 2009-09-03 2011-03-17 Rubicon Research Private Limited Compositions pharmaceutiques au goût masqué
US20110263606A1 (en) * 2010-04-26 2011-10-27 Horst Zerbe Solid oral dosage forms comprising tadalafil

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995019978A1 (fr) 1994-01-21 1995-07-27 Laboratoires Glaxo Wellcome S.A. Derives tetracycliques, leurs procedes de preparation et leur utilisation
US6821975B1 (en) * 1999-08-03 2004-11-23 Lilly Icos Llc Beta-carboline drug products
US20060286166A1 (en) * 2005-02-25 2006-12-21 Inbal Ornan Tadalafil having a large particle size and a process for preparation thereof
US20070098804A1 (en) * 2005-08-29 2007-05-03 Judith Aronhime Solid particulate tadalafil having a bimodal particle size distribution
US20070104792A1 (en) * 2005-09-13 2007-05-10 Elan Pharma International, Limited Nanoparticulate tadalafil formulations
EP1985310A1 (fr) * 2007-04-25 2008-10-29 Teva Pharmaceutical Industries Ltd. Formes de dosage solide

Also Published As

Publication number Publication date
WO2013109230A1 (fr) 2013-07-25

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