WO2001091716A1 - Systeme therapeutique par voie orale comportant du glipizide - Google Patents

Systeme therapeutique par voie orale comportant du glipizide Download PDF

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Publication number
WO2001091716A1
WO2001091716A1 PCT/CH2001/000306 CH0100306W WO0191716A1 WO 2001091716 A1 WO2001091716 A1 WO 2001091716A1 CH 0100306 W CH0100306 W CH 0100306W WO 0191716 A1 WO0191716 A1 WO 0191716A1
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WO
WIPO (PCT)
Prior art keywords
glipizide
core
therapeutic system
tablet form
form according
Prior art date
Application number
PCT/CH2001/000306
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English (en)
Inventor
Burkhard Schluetermann
Manfred Kohlmeyer
Peter Van Hoogevest
Henricus Tiemessen
Original Assignee
Add Advanced Drug Delivery Technologies 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 Add Advanced Drug Delivery Technologies Ag filed Critical Add Advanced Drug Delivery Technologies Ag
Priority to AU54592/01A priority Critical patent/AU5459201A/en
Publication of WO2001091716A1 publication Critical patent/WO2001091716A1/fr

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Classifications

    • 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
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • 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
    • A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Definitions

  • the invention relates to the field of oral dosage forms for glipizide.
  • the present invention relates to a therapeutic system for the oral administration of glipizide, comprising a compartment for a therapeutical Iy effective amount of the active ingredient glipizide, swelling agents and, optionally, water-soluble substances and to processes for the manufacture of such a system.
  • Orally administered therapeutic systems for delivering therapeutic amounts of glipizide in a controlled release way are known. They rely on a technology known as "push-pull" system and are disclosed in US Patent Specifications 4,327,725 , 4,612,008 , 5,024,843 , 5,082,668 , 5. 091,190 , 5,545,413 , 5,591,454.
  • the system can be described as a two-layered tablet surrounded by a semi-permeable membrane and a hole, which allows the body fluids to communicate with the active substance of the tablet. Glipizide can be delivered with this system at therapeutic amounts.
  • US Patent Specification 4,992,278 discloses a system which uses also the osmotic principle but achieves the controlled release of sparingly soluble active ingredients by using a one layer tablet surrounded by a semi-permeable membrane.
  • This invention discloses the use of said system for carbamazepine, nifedipine and acetylsalicylic acid.
  • a oral dosage form comprising a core consisting essentially of glipizide, a hydrophilic, polymeric swelling agent consisting of a mixture of a vinylpyrrolidone/vinyl acetate copolymer with an ethylene oxide homopolymer, optionally a water-soluble substance for inducing osmosis and, optionally, further pharmaceutically acceptable adjuncts, surrounded by a semi-permeable wall with a hole through said semi- permeable wall connecting said core with the external environment, is effectively delivering glipizide in a controlled or sustained release pattern, after wetting of the dosage form, to the external environment.
  • the present invention therefore, relates to an oral delivery form adapted to deliver glipizide
  • the therapeutic system according to the invention comprises:
  • glipizide in an amount sufficient to deliver an effective amount thereof over the intended delivery time period and ii. a hydrophilic, polymeric swelling agent consisting of a mixture of a vinylpyrrolidone/vinyl acetate copolymer with an ethylene oxide homopolymer, optionally a water-soluble substance for inducing osmosis and, optionally, further pharmaceutically acceptable adjuncts
  • controlled release is defined by the delivery of approximately constant predetermined amounts of the therapeutic agent glipizide within the time period considered (approximate zero order release).
  • Glipizide is l-cyclohexyl-3-(4-[2-(5-methylpy ⁇ azine-2-carboxamido]benzenesulphonyl)urea being used as hypo-glycaemic agent. It is administered orally in the treatment of non-insulin dependent diabetes mellitus and has a duration of action of up to 24 hours.
  • the usual initial dose is 2.5 to 5 mg daily given as a single dose 15 to 30 min before breakfast. Dosage may be adjusted at intervals of several days by amounts of 2.5 to 5 mg daily , to a maximum of 40 mg daily.
  • Glipizide is metabolized mainly in the liver and excreted chiefly in the urine, largely as inactive metabolite.(Martindale, The Extra Pharmacopoeia, 31 st Ed). Once-a-day controlled release formulations are designed to deliver up to 10 mg of the active ingredient (Physicians' Desk Reference, 52 nd Edition 1998).
  • the hydrophilic swelling agent contained in the core (a) is a polymer which interacts with water from the aqueous body fluid contained in the gastro-intestinal tract, swells and is able to expand until it reaches a state of equilibrium.
  • the swelling agent is capable of absorbing large quantities of water and of producing the swelling pressure required for the therapeutic sj'stem to function.
  • the hydrophilic, polymeric swelling agent used in the therapeutic system according to the invention consists of a mixture of a vinylpyrrolidone/vinyl acetate copolymer and an ethylene oxide homopolymer.
  • This mixture has the surprising advantage that the pressure produced during swelling does not lead to rupturing of the system and the swelling speed is unifo ⁇ n so that almost constant amounts of active ingredient are released from the system.
  • the vinylpyrrolidone/vinyl acetate copolymer component preferably has a molecular weight of 60,000.+/-.15,000.
  • the ratio of the monomer vinylpyrrolidone and vinyl acetate, which forms the basis of the copolymer, is preferably approximately 60:40 (% by weight).
  • the vinylpyrrolidone/vinyl acetate copolymer has the following properties:
  • the vinylpyrrolidone/vinyl acetate copolymer is mixed with an ethylene oxide homopolymer having a degree of polymerization of approximately 2.0 x 10 3 - 1.0 x 10 5 and a corresponding approximate molecular weight of approximately 1.0 x 10 5 - 5.0 x 10 6 and having the following properties:
  • Ethylene oxide homopolymers polyethylene glycols
  • Polyox.®. Union Carbide
  • Polyox.®. coagulant
  • a 1:1 mixture (by weight) of vinylpyrrolidone/vinyl acetate copolymer (commercial form: Kollidon.®. VA 64) and ethylene oxide homopolymer (commercial form Polyox.®. MW: 5.0 x 10 6 ) is used.
  • the hydrophilic, polymeric swelling agent can be present in the core in parts by weight of approximately 5-80%, based on the total weight of the therapeutic system in question.
  • the casing (b) made of a material that is permeable to water and impermeable to the components of the core containing the active ingredient can be in the form of a semi- permeable membrane which is permeable to water but is impermeable to the constituents contained in the core of the form of administration, such as active ingredients, swelling agents, adjuncts etc. z>
  • acylated cellulose derivatives0 (cellulose esters) that are mono-to tri-substituted by acetyl groups or mono- or di-substituted by acetyl groups and substituted by a further acyl radical other than acetyl, for example cellulose acetate, cellulose triacetate, agar acetate, amylose acetate, cellulose acetate ethyl carbamate, cellulose acetate phthalate, cellulose acetate methyl carbamate, cellulose acetate succinate, cellulose acetate dimethylaminoacetate, cellulose acetate ethyl carbonate, 5 cellulose acetate chloroacetate, cellulose acetate ethyl oxalate, cellulose acetate methyl sulphonate, cellulose acetate butyl sulphonate, cellulose acetate propionate, cellulose acetate diethylamino-acetate, cellulose esters
  • semi-permeable membrane material are hydroxypropylmethyl-cellulose and polymeric epoxides, copolymers of alkylene oxides and alkyl glycidyl ethers, polyglycols or polylactic acid derivatives and further derivatives thereof. It is also possible to use mixtures, such as, for example, of acrylates that are insoluble in water per se (for example the copolymer of acrylic acid ethyl ester and methacrylic acid methyl ester).
  • Water-soluble substances that are suitable for inducing osmosis are in principle all water- soluble substances acceptable for use in pharmacy, for example the water-soluble adjuncts mentioned in pharmacopoeias or in "Hager” as well as in Remington's Pharmaceutical Science.
  • Especially suitable are pharmaceutically acceptable water-soluble salts of inorganic or organic acids or non-ionic organic substances having an especially high degree of solubility in water, for example carbohydrates, such as sugar, or amino acids, for example glycine.
  • Such water-soluble substances for inducing osmosis are, for example, inorganic salts, such as magnesium chloride or sulfate, lithium, sodium or potassium chloride, lithium, sodium or potassium sulfate or sodium or potassium hydrogen phosphate or dihydrogen phosphate, salts of organic acids, such as sodium or potassium acetate, magnesium succinate, sodium benzoate, sodium citrate or sodium ascorbate, carbohydrates, such as arabinose, ribose or xylose (pentoses), glucose, fructose, galactose or mannose (hexoses), sucrose, maltose or lactose (disaccharides) or raffinose (trisaccharides), sugar alcohols such as mannitol, sorbitol, galactitol, inositol and xylitol, water-soluble amino acids, such as glycine, leucine, alanine or methionine, urea etc., and mixture
  • These water-soluble adjuncts can be present in the core in parts by weight of approximately 0.01-35%, based on the total weight of the therapeutic system in question.
  • Further adjuncts are, for example, plasticizers, which improve the flow properties and the handling of the hydrophilic polymeric material during the manufacture of the core, for example glycerin, triethyl citrate, diethyl phthalate, diethyl sebacate, and the like.
  • the amount of plaslicizer added is approximately from 0.01 to 20% by weight, based on the total amount of the therapeutic system.
  • surfactants for example anionic surfactants of the alkyl sulfate type, for example sodium, potassium or magnesium n-dodecyl sulphate, n-tetradecyl sulphate, n-hexadecyl sulphate or n-octadecyl sulphate, alkyl ether sulfates, for example sodium, potassium or magnesium n- dodecyloxyethyl sulphate, n-tetradecyloxyethyl sulphate, n-hexadecyl-oxyethyl sulphate or n-octadecyloxyethyl sulphate or alkanesulphonates, for example sodium, potassium or magnesium n-dodecanesulphonate, n-tetradecanesulphonate, n-hexade
  • Suitable surfactants are, in addition, non-ionic surfactants of the fatty acid/polyhydroxy alcohol ester type, such as sorbitan monolaurate, oleate, stearate or palmitate, sorbitan tristearate or rioleate, polyoxyethylene adducts of fatty acid/polyhydroxy alcohol esters, such as polyoxyethylene sorbitan monolaurate, oleate, stearate, palmitate, tristearate or trioleate, polyethylene glycol/fatty acid esters, such as polyoxyethyl stearate, polyethylene glycol-400 stearate, polyethylene glycol-2000 stearate, especially ethylene oxide/propylene oxide block polymers of the Pluronic®. (BWC) or Synperonic®. (ICI) type.
  • non-ionic surfactants of the fatty acid/polyhydroxy alcohol ester type such as sorbitan monolaurate, oleate, stearate or palmitate, sorbitan tristea
  • pulverulent carrier materials such as lactose, saccharose, sorbitol, mannitol, starch, for example potato starch, com starch or amylopectin, or cellulose, especially microcrystalline cellulose.
  • passage through the casing (b) for the transport of the constituents contained in the core into the surrounding aqueous body fluid covers apparatus as well as methods suitable for releasing the active ingredient preparation from the core of the therapeutic system.
  • the expression includes passages, openings, bores, holes and the like through the casing (b), acting as a semi-permeable membrane, which connect the surface of the casing and the core.
  • the passage can be made by mechanical drilling or laser drilling or by decomposing a degradable constituent, for example a gelatin plug, forming a passage in the casing of the therapeutic system.
  • the passage can be formed in response to the hydrostatic pressure acting on the therapeutic system.
  • two or more passages can be made at any desired point in the system.
  • the passage can also be formed by mechanical breaking up of the layers during administration of the system.
  • the passage has a minimal diameter, which is dependent on the particle size of the crystals of active ingredient.
  • the diameter of the passage must be greater than the average length of the glipizide particles.
  • the maximum diameter is likewise fixed approximately. It should not be so large that it allows aqueous body fluid to enter the therapeutic system as a result of convection.
  • the therapeutic system according to the invention can be of different shapes and can be, for example, round, oval, oblong or cylindrical or the like, and can be of various sizes depending on the amount it contains.
  • the therapeutic system can, furthermore, be transparent, colorless or colored and may carry writing to impart an individual appearance to the product and/or to make it instantly recognizable.
  • the therapeutic system according to the invention has valuable pharmacological properties and can be used in the peroral administration of an active amount of glipizide.
  • An improvement in the therapeutic effect as compared with that of solid forms of administration customary hitherto, such as tablets and dragees is achieved.
  • the drug release of the delivery form is explained by the action of water on the water soluble arid/or swelling agents contained in the core of the dosage form thus releasing constant amounts of active agents over the time period considered.
  • the action of water with the water soluble and/or swelling agents results in a build-up of osmotic pressure or swelling pressure or a combination of both. Since the semi-permeable casing (b) is rigid or at least only slightly elastic, the pressure produced by osmosis and swelling can be balanced only by release of the material contained in the core through the passage (c) in the membrane.
  • the therapeutic system according to the invention comprises:
  • glipizide in an amount sufficient to deliver an effective amount thereof over the intended delivery time period and ii. a hydrophilic, polymeric swelling agent consisting of a mixture of a vinylp3'rrolidone/vinyI acetate copolymer with an ethylene oxide homopolymer, optionally a water-soluble substance for inducing osmosis and, optionally, further pharmaceutically acceptable adjuncts
  • a core comprising i. a therapeutic active amount of glipizide between 1 and 100 mg, preferably 2 to 20 mg and ii. a 1 :1 mixture (by weight) of vinyl-pyrrolidone/vinyl acetate copolymer having a molecular weight of 60,000.+-.15,000 and a monomer ratio of approximately 60.40 (% by weight) and ethylene oxide homopolymer having a degree of polymerization of from 2,000 to 100,000, sodium or potassium chloride for inducing osmosis and optionally further pharmaceutically acceptable adjuncts
  • the present invention relates especially to a therapeutic system for the peroral administration of a therapeutic active amount of glipizide having the compositions indicated in the Examples.
  • the therapeutic system according to the invention is manufactured in accordance with processes known per se, for example by comminuting the constituents of the core, mixing them with one another, granulating them and compressing them, covering the core with a casing and, where appropriate, making the passage through the casing (a) for the transport of the constituents contained in the core, for example an opening through the semi-permeable membrane, Atficronized glipizide is mixed with the constituents forming the core of the form of administration and granulated, for example by mixing the adjuncts, sodium chloride and Polyox.®.
  • a solution of polyvinylpyrrol ⁇ done/polyvinyl acetate in an organic solvent or water removing the solvent and granulating and drying the residue.
  • the granulate is then compressed and punched out into shapes, for example tablet cores, optionally with the addition of glidants, for example magnesium stearate, of conventional shape and size; for example, approximately 5-12 mm in diameter (round shapes) and approximately 4-8 mm (in width) and 10-22 mm (in length- oblong shapes).
  • the semi-permeable casing can be applied to the core containing the active ingredient by pouring, molding, spraying or by dipping (he capsule into the material forming the semi- permeable casing.
  • Another process that can be used to apply the casing is the air suspension procedure. This process comprises suspending and tumbling the materials (capsules or capsule cores) in a stream of air and an agent forming the casing until the casing surrounds and covers the core.
  • the air suspension procedure is described in U.S. Pat. No. 2,799,241 and in J. Am. Phaxm. Assoc, Vol. 48, p.451-459, 1979, and in Volume 49, p. 82 to 84, 1980.
  • An example of other preferred standard processes is the spray pan process, which is described, in Remington's Pharmaceutical Sciences, 14th Edition, on pages 1686-1687.
  • the passage in the semi-permeable casing can be produced subsequently by mechanical drilling or using a laser.
  • the following examples illustrate the invention.
  • Glipizide which is ground to an average particle size of 5 ⁇ m, methylhydroxypropylcellulose and sodium chloride are mixed in a planet mixer. This mixture is granulated with a part of the vinylpyrrolidone/vinyl acetate copolymer dissolved in a methanol/isopropanol mixture. The mixture is forced through a sieve, and the resulting granules are dried in vacuum.
  • the dry granulate is mixed with the remainder of the vinylpyrrolidone/vinyl acetate copolymer, microcrystalline cellulose and magnesium stearate.
  • the homogeneous mixture is ' then compressed to tablets (punch size 10 mm diameter).
  • the resulting tablet cores are coated in a fluidized bed coater (Aeromatic Strea®) with an organic lacquer containing the constituents of the casing of the therapeutic system.
  • the coated tablets are dried in a drying oven at 40 °C. for 48 hours.
  • An opening about 750 ⁇ m in diameter is made in each tablet using a drill or a laser.

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  • Health & Medical Sciences (AREA)
  • Epidemiology (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)
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Abstract

Système thérapeutique pour administration par voie orale, doté d'une enveloppe qui contient du glipizide, des agents gonflants et éventuellement des substances hydrosolubles, pour la production d'une pression osmotique ou de gonflement.
PCT/CH2001/000306 2000-05-30 2001-05-17 Systeme therapeutique par voie orale comportant du glipizide WO2001091716A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU54592/01A AU5459201A (en) 2000-05-30 2001-05-17 Peroral therapeutic system comprising glipizide

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP00810471 2000-05-30
EP00810471.3 2000-05-30

Publications (1)

Publication Number Publication Date
WO2001091716A1 true WO2001091716A1 (fr) 2001-12-06

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003063823A2 (fr) * 2002-02-01 2003-08-07 Pfizer Products Inc. Systeme de distribution osmotique
WO2003092660A1 (fr) * 2002-05-06 2003-11-13 Ranbaxy Laboratories Limited Systeme monocompartiment d'administration de medicament a regulation osmotique
WO2004098572A1 (fr) * 2003-05-06 2004-11-18 Ranbaxy Laboratories Limited Liberation biphasique de glipizide contenu dans une forme pharmaceutique osmotique monocompartiment
US9089492B2 (en) 2000-11-20 2015-07-28 Warner Chilcott Company, Llc Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4992278A (en) * 1987-01-14 1991-02-12 Ciba-Geigy Corporation Therapeutic system for sparingly soluble active ingredients
US5024843A (en) * 1989-09-05 1991-06-18 Alza Corporation Oral hypoglycemic glipizide granulation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4992278A (en) * 1987-01-14 1991-02-12 Ciba-Geigy Corporation Therapeutic system for sparingly soluble active ingredients
US5024843A (en) * 1989-09-05 1991-06-18 Alza Corporation Oral hypoglycemic glipizide granulation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Martindale 32nd edition", 1999, PHARMACEUTICAL PRESS, LONDON, XP002174441 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9089492B2 (en) 2000-11-20 2015-07-28 Warner Chilcott Company, Llc Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures
WO2003063823A2 (fr) * 2002-02-01 2003-08-07 Pfizer Products Inc. Systeme de distribution osmotique
WO2003063823A3 (fr) * 2002-02-01 2003-12-04 Pfizer Prod Inc Systeme de distribution osmotique
WO2003092660A1 (fr) * 2002-05-06 2003-11-13 Ranbaxy Laboratories Limited Systeme monocompartiment d'administration de medicament a regulation osmotique
WO2004098572A1 (fr) * 2003-05-06 2004-11-18 Ranbaxy Laboratories Limited Liberation biphasique de glipizide contenu dans une forme pharmaceutique osmotique monocompartiment

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Publication number Publication date
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