WO2005025566A1 - Formulations pharmaceutiques a administration par voie orale contenant le principe actif irbesartan - Google Patents

Formulations pharmaceutiques a administration par voie orale contenant le principe actif irbesartan Download PDF

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Publication number
WO2005025566A1
WO2005025566A1 PCT/TR2004/000040 TR2004000040W WO2005025566A1 WO 2005025566 A1 WO2005025566 A1 WO 2005025566A1 TR 2004000040 W TR2004000040 W TR 2004000040W WO 2005025566 A1 WO2005025566 A1 WO 2005025566A1
Authority
WO
WIPO (PCT)
Prior art keywords
irbesartan
pharmaceutical formulations
active substance
oral pharmaceutical
new oral
Prior art date
Application number
PCT/TR2004/000040
Other languages
English (en)
Inventor
Abdullah Uslu
Original Assignee
Nobel Ilac Sanayi Ve Ticaret As
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 Nobel Ilac Sanayi Ve Ticaret As filed Critical Nobel Ilac Sanayi Ve Ticaret As
Priority to EP04775700A priority Critical patent/EP1670461A1/fr
Publication of WO2005025566A1 publication Critical patent/WO2005025566A1/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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • This innovation is related to pharmaceutical formulations containing the active ingredient named irbesartan.
  • the formulations mentioned in this innovation are the pharmaceutical formulations appropriate for an oral use and preferably presented in tablets or capsules.
  • Irbesartan is a strong and long effective non-peptide tetrazole derivative and an angiotensin II type 1 receptor (ATi) antagonist. Its chemical composition is as follows: 2-butyl-3-[[2'-(lH-tetrazol-5-yl) [1, l'-bi ⁇ henyl]-4-yl] methyl] 1, 3 -diazaspiro [4,4] non- l-en-4-one. It is used alone or with other antihypertensive agents to treat high blood
  • Irbesartan is clinically used alone as once-daily doses of 75 mg, 150 mg or 300 mg or combined with other antihypertensive agents to treat hypertension.
  • Irbesartan is defined under the patent number US5270317 and its molecular structure is as represented below:
  • Irbesartan is a white crystalline powder that is slightly soluble in alcohol and methylene chloride and insoluble in water. Resulting from the high density of the irbesartan powder, factors such as bad fluidity properties and adherence to the surfaces affect negatively this ingredient during the tablet and capsule preparation process. This is why,
  • Irbesartan After the oral administration of Irbesartan, as it is the case for some prodrugs, it is not subject to biotransformation.
  • the oral bio-availability of irbesartan is around 60-80%.
  • the peak plasma value of irbesartan is attained 1-1.5 hours after dosing and its terminal elimination half-life averages 11-15 hours.
  • the daily dosing can be started at 75 mg and raised up to 300 mg till the convenient treatment result is achieved.
  • a diuretic such as hydrochlorotiazide can complete the treatment. Hydrochlorotiazide acts like an additive to the pharmacological activity of irbesartan.
  • the patent number EP0747050 describes the pharmacological compositions that contain the active ingredient irbesartan. In this patent, apart from irbesartan, the formulation includes a diuretic. The team that prepared the invention presented in the patent EP0747050 describes a similar formulation in the patent number US5994348.
  • Irbesartan which is an angiotensin II receptor antagonist, effects as an antihypertensive on the rennin-angiotensin system by selectively blocking the angiotensin II type 1 receptors.
  • the developed antihypertensive drugs have been formulated so to reach minimum 80% of dissolution at 15 minutes after dosing and minimum 90% of dissolution at 30 minutes after dosing.
  • the formulation includes tablet or capsule form preparation that contains pharmacologically appropriate excipients. Owing to the excipients added to the formulation, the disintegration and dissolution properties of the tablet or capsule form are situated at the desired levels.
  • the following ingredients are used: - Cellactose 80 and/or spray dried lactose, pre-gelatinized starch as filling material and/or binding agent - Avicel PH 102 as filling material - Ac-di-sol as disintegrant - Poloxamer 188 as surfactant - Aerosil 200 as glidant - Magnesium stearate as lubricant
  • This formulation was prepared according to the wet granulation method.
  • Poloxamer 188 that is a non-ionic surfactant is used in our formulation in order to augment the solubility.
  • the proportion of Poloxamer 188 used in the formulation represents 0.5 - 8% of the tablet's weight, preferably 3%.
  • granulation was done with the water and alcohol solutions of Poloxamer 188.
  • irbesartan had a soluble property in alcohol and that thanks to this property better dissolution results were obtained.
  • the granulation made with alcohol gives better dissolution values than the one made with water.
  • the filling materials used in our formulation are Cellactose 80 and/or spray dried lactos ⁇ i Avicel PH 102 and pre-gelatinized starch.
  • spray dried lactose offers a bigger specific surface area.
  • the active ingredient granulized with Cellactose 80 and/or spray dried lactose gave the desired dissolution specificities thanks to the wide surface area that resulted after the disintegration of the tablets or capsules prepared according to this technique.
  • the proportion of Cellactose 80 and/or spray dried lactose used in the formulation represents 5 - 50% of the tablet's weight, preferably
  • the pre-gelatinized starch is used for the tablets prepared with the wet granulation method because of its poor fluidity properties. In the formulation, we also took advantage of the binding characteristics of the pre-gelatinized starch.
  • the disintegrant added to the formulation is the super disintegrant Ac-Di-Sol.
  • Aerosil 200 was added to the formulation to reduce the static electricity generated among the powder particles and by doing so it is aimed to improve the fluidity features.
  • the lubricant used in the formulation is magnesium stearate.
  • the compression process can be done without the tablets adhering to the tablet punch.
  • tablets were prepared by using in the same proportion lactose monohydrate instead of Cellactose 80 and/or spray dried lactose and by implementing the granulation with water and alcohol without changing the proportions of the other excipients.
  • dissolution profiles are taken into consideration, it can be noted that the formulation, subject of this innovation, leads to the best dissolution profile.
  • the figure 1 presents the compared dissolution profiles of the tablets prepared by using: - Lactose monohydrate and granulation with water (Formula 2- ⁇ * ⁇ ) - Granulation with alcohol (Formula 1- — o— ) - Cellactose 80 and granulation with alcohol (Formula 3- —*-, this is the subject of our innovation)
  • the figure 2 presents a comparative dissolution graph of the formulation according to the present invention and a product named Karvea (Karvea 300 mg * ; Irbesartan 300 mg - «--- ).
  • the tablet formulation of the active substance irbesartan according to present invention is available in 3 different dosages. These dosages respectively contain 75mg, 150 mg, and 300mg of the active substance irbesartan.
  • the table 1 presents the weight/weight % (w/w %) values of the active and inactive ingredients included in the formulation. Table 1
  • the table 2 presents the weight values of the inactive ingredients included in the 75 mg, 150mg and 300mg formulations containing the active ingredient irbesartan. Table 2
  • the table 3 presents the dissolution rates of the comparison between Karvea (contains irbesartan) and the irbesartan formulation of present invention after 5, 10, 15, 20 and 30 minutes of dissolution.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un nouveau procédé de préparation de nouvelles formes posologiques pharmaceutiques qui contiennent le principe actif irbesartan et qui sont destinées à être administrées par voie orale. Le développement de cette formulation a permis d'améliorer les caractéristiques de dissolution de l'irbesartan.
PCT/TR2004/000040 2003-09-18 2004-09-16 Formulations pharmaceutiques a administration par voie orale contenant le principe actif irbesartan WO2005025566A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP04775700A EP1670461A1 (fr) 2003-09-18 2004-09-16 Formulations pharmaceutiques a administration par voie orale contenant le principe actif irbesartan

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2003/01553A TR200301553A1 (tr) 2003-09-18 2003-09-18 İrbesartan etken maddesi içeren yeni oral farmasötik formülasyonlar
TR2003/01553 2003-09-18

Publications (1)

Publication Number Publication Date
WO2005025566A1 true WO2005025566A1 (fr) 2005-03-24

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ID=34311482

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2004/000040 WO2005025566A1 (fr) 2003-09-18 2004-09-16 Formulations pharmaceutiques a administration par voie orale contenant le principe actif irbesartan

Country Status (3)

Country Link
EP (1) EP1670461A1 (fr)
TR (2) TR200301553A1 (fr)
WO (1) WO2005025566A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1806130A1 (fr) * 2006-01-09 2007-07-11 KRKA, D.D., Novo Mesto Préparations solides comprenant du irbesartan
WO2008101375A1 (fr) * 2007-02-16 2008-08-28 Guangzhou Pui's Pharmaceutical Factory Ltd. Composition pharmaceutique de rétention gastrique à libération prolongée comprenant de l'irbesartan
WO2009065514A1 (fr) * 2007-11-19 2009-05-28 Bayer Animal Health Gmbh Stabilisation de suspensions huileuses contenant des acides siliciques hydrophobes
WO2011141783A2 (fr) 2010-04-13 2011-11-17 Micro Labs Limited Composition pharmaceutique comprenant de l'irbésartan
WO2013013657A1 (fr) * 2011-07-28 2013-01-31 Stada Arzeimittel Ag Composition pharmaceutique solide comprimée contenant du valsartan particulaire amorphe en tant que principe actif
EP2068839B1 (fr) 2006-09-27 2015-09-23 Novartis AG Composition pharmaceutique comprenant de la nilotinib ou son sel
CN107028912A (zh) * 2017-05-31 2017-08-11 珠海润都制药股份有限公司 一种厄贝沙坦胶囊的制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2065035T3 (pl) 2007-11-28 2011-02-28 Lesvi Laboratorios Sl Preparaty farmaceutyczne zawierające irbesartan

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270317A (en) * 1990-03-20 1993-12-14 Elf Sanofi N-substituted heterocyclic derivatives, their preparation and the pharmaceutical compositions in which they are present
EP0747050A1 (fr) * 1995-06-07 1996-12-11 Bristol-Myers Squibb Company Compositions pharmaceutiques d'irbésartan
US5994348A (en) * 1995-06-07 1999-11-30 Sanofi Pharmaceutical compositions containing irbesartan
WO2003035062A1 (fr) * 2001-10-26 2003-05-01 Sanofi-Synthelabo Utilisation de l'irbesartan pour la preparation de medicaments utiles pour la prevention ou le traitement de l'hypertension pulmonaire
CN1415298A (zh) * 2002-10-24 2003-05-07 王登之 一种用于治疗高血压的复方厄贝沙坦胶囊

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270317A (en) * 1990-03-20 1993-12-14 Elf Sanofi N-substituted heterocyclic derivatives, their preparation and the pharmaceutical compositions in which they are present
EP0747050A1 (fr) * 1995-06-07 1996-12-11 Bristol-Myers Squibb Company Compositions pharmaceutiques d'irbésartan
US5994348A (en) * 1995-06-07 1999-11-30 Sanofi Pharmaceutical compositions containing irbesartan
US6342247B1 (en) * 1995-06-07 2002-01-29 Sanofi-Synthelabo Pharmaceutical compositions containing irbesartan
WO2003035062A1 (fr) * 2001-10-26 2003-05-01 Sanofi-Synthelabo Utilisation de l'irbesartan pour la preparation de medicaments utiles pour la prevention ou le traitement de l'hypertension pulmonaire
CN1415298A (zh) * 2002-10-24 2003-05-07 王登之 一种用于治疗高血压的复方厄贝沙坦胶囊

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Section Ch Week 200374, Derwent World Patents Index; Class A96, AN 2003-780161, XP002309232 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1806130A1 (fr) * 2006-01-09 2007-07-11 KRKA, D.D., Novo Mesto Préparations solides comprenant du irbesartan
WO2007080074A1 (fr) * 2006-01-09 2007-07-19 Krka, D.D. Novo Mesto Composition pharmaceutique solide comprenant de l’irbesartan
EA016579B1 (ru) * 2006-01-09 2012-06-29 Крка, Д.Д. Ново Место Твердый фармацевтический препарат, содержащий гидрохлорид ирбесартана, и способ его изготовления
EP2068839B1 (fr) 2006-09-27 2015-09-23 Novartis AG Composition pharmaceutique comprenant de la nilotinib ou son sel
WO2008101375A1 (fr) * 2007-02-16 2008-08-28 Guangzhou Pui's Pharmaceutical Factory Ltd. Composition pharmaceutique de rétention gastrique à libération prolongée comprenant de l'irbesartan
WO2009065514A1 (fr) * 2007-11-19 2009-05-28 Bayer Animal Health Gmbh Stabilisation de suspensions huileuses contenant des acides siliciques hydrophobes
US9095511B2 (en) 2007-11-19 2015-08-04 Bayer Intellectual Property Gmbh Stabilization of oily suspensions comprising hydrophobic silicas
WO2011141783A2 (fr) 2010-04-13 2011-11-17 Micro Labs Limited Composition pharmaceutique comprenant de l'irbésartan
WO2013013657A1 (fr) * 2011-07-28 2013-01-31 Stada Arzeimittel Ag Composition pharmaceutique solide comprimée contenant du valsartan particulaire amorphe en tant que principe actif
CN107028912A (zh) * 2017-05-31 2017-08-11 珠海润都制药股份有限公司 一种厄贝沙坦胶囊的制备方法

Also Published As

Publication number Publication date
TR200601092T1 (tr) 2006-08-21
TR200301553A1 (tr) 2005-10-21
EP1670461A1 (fr) 2006-06-21

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