WO2000007596A1 - Formulation pharmaceutique soluble dans l'eau pour l'utilisation de sildenafil - Google Patents

Formulation pharmaceutique soluble dans l'eau pour l'utilisation de sildenafil Download PDF

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Publication number
WO2000007596A1
WO2000007596A1 PCT/EP1999/005464 EP9905464W WO0007596A1 WO 2000007596 A1 WO2000007596 A1 WO 2000007596A1 EP 9905464 W EP9905464 W EP 9905464W WO 0007596 A1 WO0007596 A1 WO 0007596A1
Authority
WO
WIPO (PCT)
Prior art keywords
water
pharmaceutical formulation
soluble pharmaceutical
sildenafil
formulation according
Prior art date
Application number
PCT/EP1999/005464
Other languages
German (de)
English (en)
Inventor
Thomas Strüngmann
Original Assignee
Hexal Ag
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 Hexal Ag filed Critical Hexal Ag
Priority to AU54156/99A priority Critical patent/AU5415699A/en
Publication of WO2000007596A1 publication Critical patent/WO2000007596A1/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
    • A61K31/33—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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence

Definitions

  • the invention relates to a pharmaceutical formulation to be dissolved in water, which contains the phosphodiesterase (PDE) type 5 inhibitor sildenafil or its pharmaceutically acceptable salts as active ingredient.
  • PDE phosphodiesterase
  • Sildenafil [1- (4-ethoxy-3- (6,7-dihydro-1-methyl-7-oxo-3-propyl 1H-pyazolo (4,3-d) pyrimidin-5-yl) phenylsulfonyl) -4-methyl piperazin] is a very selective cyclic guanosine monophosphate (cGMP) -specific phosphodiesterase (PDE) type 5 inhibitor, which was developed for the treatment of both organic and psychologically related impotence.
  • cGMP cyclic guanosine monophosphate
  • PDE phosphodiesterase
  • nitric oxide NO
  • NO nitric oxide
  • cGMP cyclic guanosine monophosphate
  • Sildenafil does not have a direct relaxing effect on the erectile tissue, but it enhances the effect of the nitrogen oxide by inhibiting phosphodieseterase type 5 (PDE 5), which is responsible for the breakdown of cGMP in the erectile tissue.
  • sildenafil of the cGMP levels in the erectile tissue, so that the smooth muscles relax and the blood can penetrate into the erectile tissue.
  • the effect of sildenafil is absent at the recommended dosage but lacks sexual stimulation.
  • sildenafil has been administered orally, in the form of a tablet with an active substance content of 25 mg, 50 mg or 100 mg / day, the bioavailability being only 40%.
  • the active substance content normally administered is 50 mg / day.
  • the tablet should be taken at least one hour, and if fat foods were consumed, 1.5 hours before use. The patient's sexual behavior is therefore somewhat spontaneous, which is a very considerable limitation for them.
  • the object of the invention is to provide a pharmaceutical formulation for the use of sildenafil or its pharmaceutically acceptable salts which can be quickly dissolved in water, in order to achieve the therapeutically effective blood plasma level more quickly and to improve patient compliance by easier intake .
  • the pharmaceutical formulation to be dissolved in water should also be sugar-free.
  • the active ingredient and the sweetener are chemically compatible and are suitable for producing the desired form of the drug and the associated work steps.
  • an orally administrable, water-soluble pharmaceutical formulation which contains, as active ingredient, the phosphodiesterase (PDE) type 5 inhibitor sildenafil or its pharmaceutically acceptable salts.
  • PDE phosphodiesterase
  • Possible salts are the acid addition salts such as the hydrochlorides or the halides, sulfates, phosphates, citrates, acetates, maleates, succinates, fumarates, ascorbates and carbonates.
  • Sildenafil or its pharmaceutically acceptable salts can also be used in combination with other known active compounds, especially specific and non-specific cytochrome P450 (CYP) inhibitors.
  • CYP cytochrome P450
  • sildenafil By combining sildenafil with a CYP inhibitor such as erythromycin, cimetidine, ketoconazole, itraconazole or mibefradil, the concentration in the blood plasma is greatly increased and the breakdown or excretion is delayed. The rapid flooding is thus maintained or accelerated with a reduced amount of sildenafil.
  • a CYP inhibitor such as erythromycin, cimetidine, ketoconazole, itraconazole or mibefradil
  • the amount of sildenafil, preferably in the form of a pharmaceutically acceptable salt, which is used in the pharmaceutical formulation according to the invention to be dissolved in water, can be between 20 to 150 mg and will preferably be in the range from 25 to 100 mg per dosage unit.
  • the pharmaceutical formulation which can be quickly dissolved in water can be in the form of effervescent tablets, granules or tabs.
  • the carbonate and / or the bicarbonate of the alkali and alkaline earth metals in combination with an acid can be used as the carbon dioxide source.
  • the weight ratio of the acid to the carbonate and / or bicarbonate can be between 0.9 and 1.6.
  • sweetener in particular aspartame, cyclamate and saccharin or their sodium salts.
  • binders and lubricants fillers, surfactants, disintegrants, flavoring agents and other customary auxiliaries which are customary for these dosage forms.
  • Effervescent tablet sildenafil citrate 70.23 mg (corresponds to 50 mg sildenafil)

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Gynecology & Obstetrics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une formulation pharmaceutique pouvant se dissoudre rapidement dans l'eau, renfermant comme constituant actif le sildenafil, inhibiteur 5 de type (PDE) de phosphodiestérase, ou un sel pharmaceutiquement acceptable de celui-ci.
PCT/EP1999/005464 1998-07-31 1999-07-30 Formulation pharmaceutique soluble dans l'eau pour l'utilisation de sildenafil WO2000007596A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU54156/99A AU5415699A (en) 1998-07-31 1999-07-30 Water-soluble pharmaceutical formulation for administering sildenafil

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19834507A DE19834507A1 (de) 1998-07-31 1998-07-31 Pharmazeutische, wasserlösliche Tablettenformulierung zur Anwendung von Sildenafil
DE19834507.0 1998-07-31

Publications (1)

Publication Number Publication Date
WO2000007596A1 true WO2000007596A1 (fr) 2000-02-17

Family

ID=7875941

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/005464 WO2000007596A1 (fr) 1998-07-31 1999-07-30 Formulation pharmaceutique soluble dans l'eau pour l'utilisation de sildenafil

Country Status (3)

Country Link
AU (1) AU5415699A (fr)
DE (1) DE19834507A1 (fr)
WO (1) WO2000007596A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004017976A1 (fr) * 2002-08-21 2004-03-04 Phoqus Pharmaceuticals Limited, Forme psologique orale a gout masque, a dissolution rapide et comprenant du sildenafil
KR100435514B1 (ko) * 2002-03-22 2004-06-10 한미약품 주식회사 실데나필 젖산염의 속효제형
EP1469852A2 (fr) * 2002-01-04 2004-10-27 Henry Ford Health System Donneurs de monoxyde d'azote pour le traitement de maladies et de blessures
FR3013221A1 (fr) * 2013-11-19 2015-05-22 Nabil Said Composition pharmaceutique effervescente a base de sildenafil et son procede de fabrication

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0015239D0 (en) * 2000-06-21 2000-08-16 Biochemie Gmbh Organic compounds
BRPI0003386B8 (pt) 2000-08-08 2021-05-25 Cristalia Produtos Quim Farmaceuticos Ltda pró-droga homo ou heterodiméricas úteis no tratamento de doenças ou disfunções mediadas por fosfodiesterases; composições farmacêuticas contendo a pró-droga ou seus sais farmacêuticos aceitáveis; processo de obtenção destas pró-drogas
GB0606234D0 (en) * 2006-03-29 2006-05-10 Pliva Istrazivanje I Razvoj D Pharmaceutically acceptable salts and polymorphic forms

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0463756A1 (fr) * 1990-06-20 1992-01-02 Pfizer Limited Pyrazolopyrimidones comme agents antiangineux
WO1998030209A1 (fr) * 1997-01-06 1998-07-16 Pfizer Pharmaceuticals Inc. Forme galenique pharmaceutique a liberation rapide et masquant le gout
JPH10298062A (ja) * 1997-04-24 1998-11-10 Pfizer Pharmaceut Co Ltd 口腔内速溶型錠剤
WO1998052569A1 (fr) * 1997-05-19 1998-11-26 Zonagen, Inc. Therapie combinatoire permettant de moduler la reponse sexuelle chez un patient
WO1999027905A1 (fr) * 1997-12-02 1999-06-10 West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited Compositions pour administration nasale
WO1999030688A1 (fr) * 1997-12-13 1999-06-24 Anthony Auffret Procedes de lyophilisation de solutions
EP0951908A2 (fr) * 1998-02-23 1999-10-27 Pfizer Limited Methode de traitement de l'impuissance due à des lésions de la moelle épinière

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0463756A1 (fr) * 1990-06-20 1992-01-02 Pfizer Limited Pyrazolopyrimidones comme agents antiangineux
WO1998030209A1 (fr) * 1997-01-06 1998-07-16 Pfizer Pharmaceuticals Inc. Forme galenique pharmaceutique a liberation rapide et masquant le gout
JPH10298062A (ja) * 1997-04-24 1998-11-10 Pfizer Pharmaceut Co Ltd 口腔内速溶型錠剤
WO1998052569A1 (fr) * 1997-05-19 1998-11-26 Zonagen, Inc. Therapie combinatoire permettant de moduler la reponse sexuelle chez un patient
WO1999027905A1 (fr) * 1997-12-02 1999-06-10 West Pharmaceutical Services Drug Delivery & Clinical Research Centre Limited Compositions pour administration nasale
WO1999030688A1 (fr) * 1997-12-13 1999-06-24 Anthony Auffret Procedes de lyophilisation de solutions
EP0951908A2 (fr) * 1998-02-23 1999-10-27 Pfizer Limited Methode de traitement de l'impuissance due à des lésions de la moelle épinière

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 130, no. 4, 25 January 1999, Columbus, Ohio, US; abstract no. 43379, ITO, AKINORI ET AL: "Tablets rapidly soluble in the oral cavity and manufacture thereof" XP002121794 *
PFIZER, INC: "PRODUCT FACT SHEET: Viagra (sildenafil citrate) Tablets", IMMEDIATE PHARMACEUTICAL SERVICES, INC, March 1998 (1998-03-01), XP002123129 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1469852A2 (fr) * 2002-01-04 2004-10-27 Henry Ford Health System Donneurs de monoxyde d'azote pour le traitement de maladies et de blessures
EP1469852A4 (fr) * 2002-01-04 2009-12-02 Ford Henry Health System Donneurs de monoxyde d'azote pour le traitement de maladies et de blessures
KR100435514B1 (ko) * 2002-03-22 2004-06-10 한미약품 주식회사 실데나필 젖산염의 속효제형
WO2004017976A1 (fr) * 2002-08-21 2004-03-04 Phoqus Pharmaceuticals Limited, Forme psologique orale a gout masque, a dissolution rapide et comprenant du sildenafil
FR3013221A1 (fr) * 2013-11-19 2015-05-22 Nabil Said Composition pharmaceutique effervescente a base de sildenafil et son procede de fabrication

Also Published As

Publication number Publication date
AU5415699A (en) 2000-02-28
DE19834507A1 (de) 2000-02-03

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