WO2004098572A1 - Liberation biphasique de glipizide contenu dans une forme pharmaceutique osmotique monocompartiment - Google Patents

Liberation biphasique de glipizide contenu dans une forme pharmaceutique osmotique monocompartiment Download PDF

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Publication number
WO2004098572A1
WO2004098572A1 PCT/IB2004/001424 IB2004001424W WO2004098572A1 WO 2004098572 A1 WO2004098572 A1 WO 2004098572A1 IB 2004001424 W IB2004001424 W IB 2004001424W WO 2004098572 A1 WO2004098572 A1 WO 2004098572A1
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WIPO (PCT)
Prior art keywords
delivery system
osmotic controlled
cellulose acetate
controlled delivery
monocompartment
Prior art date
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PCT/IB2004/001424
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English (en)
Inventor
Ramakrishnan Sankar
Narayanan Badri Viswanathan
Rajeev Singh Raghuvanshi
Ashok Kumar Rampal
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Ranbaxy Laboratories Limited
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Filing date
Publication date
Priority claimed from PCT/IB2003/001771 external-priority patent/WO2003092660A1/fr
Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Priority to EP04731419A priority Critical patent/EP1622591A1/fr
Publication of WO2004098572A1 publication Critical patent/WO2004098572A1/fr

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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/734—Alginic acid
    • 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
    • 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
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer

Definitions

  • the present invention relates to a monocompartment osmotic controlled delivery system of glipizide, providing a biphasic release of glipizide.
  • the elementary oral osmotic system takes the form of a conventional coated tablet. It comprises a homogenous core tablet of drug coated with a semi-permeable wall/layer and an aperture created through the wall for the release of contents from the core.
  • OROS ® osmotic pressure controlled drug delivery
  • the elementary oral osmotic system takes the form of a conventional coated tablet. It comprises a homogenous core tablet of drug coated with a semi-permeable wall/layer and an aperture created through the wall for the release of contents from the core.
  • water permeates into the core through the semipermeable wall and dissolves the drug.
  • the osmotic pressure thus built, exerts pressure against the wall and thereby releases the solution of drug, through the aperture in the wall.
  • Osmotic controlled drug delivery systems show better in vitro-in vivo correlation as their performance is reported to be independent of pH and contents of the gastrointestinal tract. Moreover, they can be resistant to mechanical stress encountered within the gut.
  • the use of simple osmotic systems is confined to a limited number of drugs which are soluble enough to produce a sufficiently high osmotic pressure. Sparingly soluble drugs fail to be delivered from this system in the desired manner, and therefore demand skillful modifications to exploit the advantages of these osmotic delivery systems.
  • European Patent Application No. 52917 describes osmotic systems without the elastic diaphragm.
  • the osmotic system disclosed in this patent application has the two compartments of the push pull system replaced by two different composition layers, viz., drug layer containing drug and osmotic agents, and an expandable driving member layer formed of a water swellable hydrogel that absorbs fluid imbibed into the compartment and expands from a rested to an expanded state. The expansion of the driving member exerts pressure on the drug layer forcing its content out of the aperture.
  • 4,992,278 discloses a monocompartment therapeutic system comprising (a) a casing made of a material that is permeable to water and is impermeable to the components of the core containing the active ingredient, (b) a core containing an active ingredient that is sparingly soluble in water or a mixture of such active ingredients, a hydrophilic polymeric swelling agent consisting of a mixture of a vinylpyrrolidone / vinyl acetate copolymer with an ethylene oxide homopolymer, optionally water soluble substance for inducing osmosis and optionally further pharmaceutically acceptable adjuncts and (c) passage through the casing (a) for the transport of the constituents contained in the core into the surrounding aqueous body fluid.
  • this patent teaches that the use of conventional swelling agents of two-compartment system such as polyvinylpyrrolidone, polyethylene oxide, polymethacrylate and the like, in single compartment system does not work. This is because the swelling pressure of these polymers is so great that in contact with water the semipermeable membrane bursts and the whole system disintegrates in the stomach after a short period of time.
  • two-compartment system such as polyvinylpyrrolidone, polyethylene oxide, polymethacrylate and the like
  • the use of at least one alginic acid derivative as swelling agent in monocompartment osmotic-controlled drug delivery systems can overcome problems associated with conventional osmotic-controlled systems and helps in achieving desired controlled drug release profiles for a poorly soluble drug.
  • the use of a alkali metal or alkali earth metal derivative in the monocompartment osmotic controlled delivery system of glipizide helps to achieve biphasic release of drugs, for example, glipizide.
  • a monocompartment osmotic controlled delivery system of glipizide for biphasic release comprising glipizide, at least one alginic acid derivative, and at least one alkali metal or alkali earth metal derivative.
  • a monocompartment osmotic controlled delivery system of glipizide for biphasic release comprising:
  • a monocompartment osmotic controlled delivery system of glipizide for biphasic release comprising:
  • a process for the preparation of a monocompartment osmotic controlled delivery system of glipizide for biphasic release comprising the steps of: (a) blending glipizide, at least one alginic acid derivative, at least one alkali metal or alkali earth metal derivative , an osmotic agent and at least one pharmaceutically acceptable inert excipient; optionally granulating the blend with a binder; and compressing the blend /granules into a compact core;
  • a method of achieving biphasic in-vitro release of glipizide from a monocompartment osmotic controlled drug delivery system comprising glipizide, at least one alginic acid derivative, and at least one alkali metal or alkali earth metal derivative.
  • a method of achieving biphasic in-vivo release of glipizide from a monocompartment osmotic controlled drug delivery system comprising glipizide, at least one alginic acid derivative, and at least one alkali metal or alkali earth metal derivative.
  • a method of achieving biphasic in-vitro release of glipizide from a monocompartment osmotic controlled drug delivery system comprising glipizide, at least one alginic acid derivative, and at least one alkali metal or alkali earth metal derivative; wherein the second phase of glipizide release starts between about 3 to about 12 hours.
  • a method of achieving biphasic in-vivo release of glipizide from a monocompartment osmotic controlled drug delivery system comprising glipizide, at least one alginic acid derivative, and at least one alkali metal or alkali earth metal derivative; wherein the second phase of glipizide release starts between about 3 to about 12 hours.
  • Figure 1 is a graph, which compares the in vitro release of glipizide from monocompartment osmotic system of Examples 1-4, and commercially available Glucotrol XL ® (10 mg), marketed by Pfizer.
  • Figure 2 is a graph, which compares the in vivo mean plasma concentration profiles (12 subjects) of glipizide, obtained on oral administration of monocompartment osmotic system of the present invention and commercially available Glucotrol XL ® (10 mg), marketed by Pfizer.
  • Glucotrol XL ® 10 mg
  • Alginic acid derivative used as a swelling agent in the monocompartment osmotic controlled drug delivery system possess the required swelling property to form a dispersion of the poorly soluble drug of a consistency, which is easily flowable through the passageway without damaging the semipermeable membrane. Combination of above attributes is rarely found amongst conventionally used swelling agents in osmotic systems.
  • the amount of alginic acid derivative used in the core may be varied over a wide range. Most of the alginic acid derivatives are proved to be non-toxic to humans and other mammals on oral administration and are approved for human consumption.
  • monocompartment osmotic controlled system may be designed to provide a biphasic release of drug. The rate of drug release may also be manipulated by controlling the thickness and nature of semipermeable membrane, i.e., with proper choice of other coating additives.
  • biphasic release refers to two different phases of release of glipizide from the dosage form, with or without a preceding lag time. The appearance of second phase of release may be detected with a sudden increase in the rate of release at the beginning of the second phase.
  • swelling refers to increase in the volume on coming in contact to water. In some cases swelling may even lead to a formation of gel like consistency into which the poorly soluble drug is embedded in the form of dispersion. Hence, the terms “swelling” and “gelling” are used interchangeably herein.
  • core covers any compact composition having a defined shape such as tablet, mold, capsule and the like.
  • poorly soluble drug as used herein includes drugs having solubility of about 1 part in 25 or more parts of water. It also includes those drugs wherein 1 part of drug dissolves in less than 25 parts of water, but under acidic or alkaline conditions, or under the influence of other excipients the solubility is decreased up to 1 in 25 parts of water.
  • Suitable examples of the therapeutic classes include antidiabetics, antineoplastic agents, antihypertensives, psychopharmacological agents, cardiovascular agents, platelet aggregation inhibitors, analgesics, antimicrobials, diuretics, spasmolytics and the like.
  • Specific examples of poorly soluble drugs include glipizide, doxazosin, verapamil, prazosin, isradipine, cilostazol, nifedipine, nisoldipine, bendroflumethazide, chlorpropamide, hydrocortisone, ibuprofen, diclofenac, and the like, and combinations thereof.
  • drug as used herein include free drug as well as any pharmaceutically acceptable salt thereof.
  • the poorly soluble drug as used herein may be in a commercially available form as such; or in a processed form using techniques of comminution, micro emulsification, co-melting, spray drying, co-processing with pharmaceutically acceptable inert excipients, drug-inclusion complexation and the like.
  • Alginic acid derivative as used herein include alginic acid as well as any of its pharmaceutically acceptable derivative such as salts, esters, and the like, and mixtures thereof. Specific examples of alginic acid salts include salts of alginic acid with sodium, potassium, magnesium, calcium or ammonia.
  • alginic acid esters include propylene glycol alginate.
  • Alginic acid is a naturally occurring hydrophilic colloidal polysaccharide consisting mainly of residues of ⁇ -l,4-linked D-mannuronic acid and ⁇ -l,4-linked L- glucuronic acid. Depending on the species of kelp used in manufacturing, ratios of mannuronic acid to glucuronic acid content typically range from 0.4 to 0.9.
  • Alginic acid has an average molecular weight varying from about 10,000-6,00,000 and is widely used in the pharmaceutical field as a stabilizer, thickener, gelling agent and emulsifier.
  • Alginic acid derivatives are marketed by ISP alginates as white to yellowish brown filamentous, grainy, granular or powdered form under the trade names - KELACLO®, ALGINIC ACID HF D, ALGINIC ACID DC, KELTONE® LVCR, KELTONE® HVCR, MANUCOL® LKX, MANUCOL LB, MANUCOL DMF, KELCOSOL®, MANUGEL® DMB, KELCOLOID® LVF, MANUCOL ESTER ERK, Improved KELMAR®, KELTOSE ®, and many others. Based on the grade used and desired drug release profile, the amount of alginic acid derivative may vary from about 5% to about 98% by weight of the total weight of core.
  • One way of achieving proper dispersion of alginic acid derivative particles is blending with an osmotic agent, which diminishes its tendency to form lumps. Further, the osmotic agent may be used to manipulate the viscosity of the dispersion of poorly soluble drug formed in the core, and also to manipulate drug release profile.
  • osmotic agent includes all pharmaceutically acceptable inert water soluble compounds suitable for inducing osmosis, referred to in the Pharmacoepias, or in “Hager” as well as in Remington's Pharmaceutical sciences.
  • Examples of compounds suitable as osmotic agents include water soluble salts of inorganic acids such as magnesium chloride or magnesium sulfate, lithium chloride, sodium chloride, potassium chloride, lithium hydrogen phosphate, sodium hydrogen phosphate, potassium hydrogen phosphate, lithium dihydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate; water soluble salts of organic acids such as sodium acetate, potassium acetate, magnesium succinate, sodium benzoate, sodium citrate, sodium ascorbate; non ionic organic compounds with high water solubility e.g.
  • inorganic acids such as magnesium chloride or magnesium sulfate, lithium chloride, sodium chloride, potassium chloride, lithium hydrogen phosphate, sodium hydrogen phosphate, potassium hydrogen phosphate, lithium dihydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate
  • water soluble salts of organic acids such as sodium acetate, potassium acetate, magnesium succinate, sodium benzoate, sodium citrate, sodium as
  • osmotic agent used in the core may be up to about 60% by weight of the total weight of core.
  • "Semipermeable membrane” as used herein is a membrane or coating, which allows movement of water molecules through it, but does not allow contents of the core to pass through.
  • Semipermeable membrane comprises membrane forming polymer and other pharmaceutically acceptable coating additives.
  • Membrane forming polymers are those, which are not metabolized in the gastrointestinal tract, i.e. are ejected unchanged from the body in feces.
  • Membrane forming polymers include those known in the art for fabrication of semipermeable membrane and described in the literature, e.g. in U.S. Patent Nos. 3,916, 899 and 3,977,404.
  • semipermeable membrane forming polymers include cellulose derivatives such as 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, cellulose acetate chloroacetate, cellulose acetate ethyl oxalate, cellulose acetate methyl sulphonate, cellulose acetate butyl sulphonate, cellulose acetate propionate, cellulose acetate diethylamino-acetate, cellulose acetate octate, cellulose acetate laurate, cellulose acetate p-toluenesulphonate, cellulose acetate butyrate; polymeric epoxides; copolymers of alkylene oxides and
  • a combination of cellulose acetates with different degrees of acetylation may be used as membrane forming polymer. As the degree of acetylation of cellulose acetate increases, permeability of the membrane decreases. In particular, a combination of cellulose acetates having acetyl content in the range of about 8% to about 50%) may be used. Further, other coating additives may be combined with the membrane forming polymers to adjust the permeability to our choice. Controlling membrane thickness also helps to manipulate the permeability of the membrane, which may vary from about 3% to about 40% weight build up over the weight of core.
  • passageway covers any suitable means for releasing the contents of the core into the surrounding media.
  • the term includes passages, apertures, bores, holes, openings and the like, created through the semipermeable membrane and forming a connection between the core and the surrounding media.
  • the passageway may be created by mechanical drilling or laser drilling, or formed in response to the osmotic pressure acting on the drug delivery system. Based on the nature of desired drug release profile, the number and diameter of the passageway may be adjusted. However, the diameter of the passageway should not be large enough to allow body fluids to enter the drug delivery system by the process of convection.
  • pharmaceutically acceptable inert excipients includes all excipients used in the art of manufacturing osmotic controlled dosage forms and described in the literature. Examples include binders, diluents, surfactants, pH modifiers, lubricants/glidants, stabilizers, plasticizers, coloring agents, and the like, and mixtures thereof.
  • binders include methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, and the like, and mixtures thereof.
  • diluents include calcium carbonate, calcium phosphate- dibasic, calcium phosphate-tribasic, calcium sulfate, cellulose-microcrystalline, cellulose powdered, dextrates, dextrins, dextrose excipients, fructose, kaolin, lactitol, lactose, mannitol, sorbitol, starch, starch pregelatinized, sucrose, sugar compressible, sugar confectioners, and the like, and mixtures thereof.
  • Surfactants may be used to promote wetting of poorly soluble drug as well as promote hydration of alginic acid derivative and include both non-ionic and ionic (cationic, anionic and zwitterionic) surfactants suitable for use in pharmaceutical compositions.
  • polyethoxylated fatty acids and its derivatives for example polyethylene glycol 400 distearate, polyethylene glycol - 20 dioleate, polyethylene glycol 4 -150 mono dilaurate, polyethylene glycol -20 glyceryl stearate; alcohol - oil transesterification products, for example polyethylene glycol - 6 corn oil; polyglycerized fatty acids, for example polyglyceryl - 6 pentaoleate; propylene glycol fatty acid esters, for example propylene glycol monocaprylate; mono and diglycerides for example glyceryl ricinoleate; sterol and sterol derivatives; sorbitan fatty acid esters and its derivatives, for example polyethylene glycol - 20 sorbitan monooleate, sorbitan monolaurate; polyethylene glycol alkyl ether or phenols, for example polyethylene glycol - 20 cetyl ether, polyethylene glycol - 10 - 100 nonyl
  • polystyrene resin for example sodium caproate, sodium glycocholate, soy lecithin, sodium stearyl fumarate, propylene glycol alginate, octyl sulfosuccinate disodium, palmitoyl carnitine; and the like; and mixtures thereof.
  • ionic surfactants for example sodium caproate, sodium glycocholate, soy lecithin, sodium stearyl fumarate, propylene glycol alginate, octyl sulfosuccinate disodium, palmitoyl carnitine; and the like; and mixtures thereof.
  • the pH modifiers are substances, which help in maintaining the pH of the local environment surrounding the drug at a value favorable for suitably modifying the solubility behavior of drug and or gelling behavior of alginic acid derivative.
  • Specific examples of pH modifiers include meglumine, trimethanolamine, ammonia, diethanolamine, ethylenediamine, L-lysine; alkali metal derivatives like dibasic sodium phosphate, sodium ascorbate, sodium citrate, tertiary sodium phosphate, sodium hydroxide and potassium hydroxide; alkali earth metal derivatives like light magnesium oxide, heavy magnesium oxide, magnesium hydroxide, calcium hydroxide, and the like, and mixtures thereof.
  • alkali metal or alkali earth metal derivatives in monocompartment osmotic controlled delivery systems of glipizide may help to achieve biphasic release.
  • alkali metal derivatives include dibasic sodium phosphate, sodium ascorbate, sodium citrate, tertiary sodium phosphate, sodium hydroxide and potassium hydroxide; alkali earth metal derivatives include light magnesium oxide, heavy magnesium oxide, magnesium hydroxide, calcium hydroxide, and the like, and mixtures thereof.
  • magnesium oxide or magnesium hydroxide may be used.
  • concentration of alkali metal or alkali earth metal derivative may vary from about 0.1% w/w to about 30% w/w of the core.
  • lubricants/glidants include colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated castor oil, sucrose esters of fatty acid, macrocrystalline wax, yellow beeswax, white beeswax, and the like, and mixtures thereof.
  • plasticizers include acetylated triacetin, triethylcitrate, tributylcitrate, glyceroltributyrate, monoglyceride, rape oil, olive oil, sesame oil, acetyltributylcitrate, acetyltriethylcitrate, glycerin sorbitol, diethyloxalate, diethyl phthalate, diethylmalate, diethylfumarate, dibutylsuccinate, diethylmalonate, dioctylphthalate, dibutylsebacate, and the like, and mixtures thereof.
  • Stabilizers include antioxidants, buffers, acids, and the like, and mixtures thereof.
  • Coloring agents include any FDA approved colors for oral use, and mixtures thereof.
  • coating additives includes all conventional coating additives used in the art of coating technology and described in the literature. Examples include flux enhancers as well as those described above under pharmaceutically acceptable inert excipients.
  • Flux enhancers are water soluble substances, which aid in drawing water from the surrounding media and are thereby helpful in manipulating the semipermeable membrane's permeability. Specific examples include hydroxymethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, hydroxypropylcellulose, propylene glycol, polyvinylpyrrolidone, and the like, and mixtures thereof.
  • the monocompartment osmotic controlled delivery system of glipizide for biphasic release may be prepared by processes known in the prior art, e.g. by comminuting, mixing, granulation, sizing, filling, molding, spraying, immersing, coating etc.
  • the core may be prepared by blending a poorly soluble drug, at least one alginic acid derivative, at least one magnesium derivative, optionally an osmotic agent and other pharmaceutically inert excipients; optionally granulating the blend; and compressing the blend/granules in to a compact core.
  • the core may be enclosed within a semipermeable membrane by applying the enclosing composition in the form of a solution/dispersion comprising semipermeable membrane forming polymer and coating additives. Finally a passageway may be created through the semipermeable membrane using a suitable technique.
  • solvents used for the purpose of granulation or for preparing solution/dispersion of the coating composition include dichloromethane, isopropyl alcohol, acetone, methanol, ethanol, water, and the like, and mixtures thereof.
  • additional coating layers may be applied over the cores either below or/and over the semipermeable membrane.
  • the additional layers comprise coating additives and provide smooth surfaces; over which semipermeable membrane may be uniformly applied or identification marks may be printed. In addition it promotes aesthetic appeal.
  • the monocompartment osmotic controlled delivery system may be coated with an immediate release layer comprising the same drug as in the core or a different drug, over the semipermeable membrane.
  • a combination of more than one drug may also be used in the core and/or in the immediate release layer.
  • Glipizide, light magnesium oxide/magnesium hydroxide, sodium alginate, sorbitol and aerosil were sieved and mixed together to form a homogenous blend.
  • Polyethylene glycol, poloxamer, and polyvinyl pyrrolidone were dispersed in a mixture of isopropyl alcohol and water (75:25 w/w) to form a dispersion of 35% w/w (except for example 4 where the concentration was 43% w/w).
  • step 3 The blend of step 1 was granulated with the dispersion of step 2.
  • the wet granules were dried in a fluidized bed drier and sized through suitable sieves.
  • the dried granules were lubricated by blending with magnesium stearate and compressed into round concave shaped cores using suitable tooling.
  • Hydroxypropyl methylcellulose and polyethylene glycol of the precoating composition were dissolved in a mixture of isopropyl alcohol and dichloromethane (60:40 w/w) to prepare a 5% w/w solution.
  • step 5 Cores of step 5 (Only Example 1) were coated with the solution of step 6 in a coating pan to form a precoated core.
  • step 8 Cellulose acetate and polyethylene glycol were dissolved in a mixture of acetone and water (90:10 w/w) to prepare a 4% w/w solution.
  • Precoated cores of step 7 (only Example 1) or cores of step 5 were coated with the solution of step 8 to form the semipermeable coating; and dried in hot air oven.
  • An orifice was drilled through the semipermeable membrane of coated cores of step 9 using a 0.6 mm mechanical drill to obtain monocompartment osmotic controlled delivery system of glipizide.
  • step 1 was granulated with the solution of step 2. 4.
  • the wet granules were dried in a fluidized bed drier and sized through suitable sieves.
  • the dried granules were lubricated by blending with magnesium stearate and compressed into round concave shaped cores using suitable tooling.
  • step 5 Cores of step 5 were coated with the solution of step 6 in a coating pan to form a precoated core.
  • Precoated cores of step 7 were coated with the solution of step 8 to form the semipermeable coating; and dried in hot air oven.
  • Figure 1 reveals that there is a sudden increase in the rate of glipizide release from the composition as per Examples 1 and 2, beginning around 6 hours, indicating the biphasic release.
  • compositions as per examples 3 and 4 which do not have alkali metal or alkaline earth metal derivative, and Glucotrol XL ® (Example 5) released glipizide at a more or less uniform rate throughout.
  • the monocompartment osmotic controlled system may help to achieve a higher concentration of glipizide during the next meal, when it is actually desired.

Abstract

La présente invention concerne un système d'administration contrôlée osmotique monocompartiment de glipizide, permettant une libération biphasique de ce dernier.
PCT/IB2004/001424 2003-05-06 2004-05-06 Liberation biphasique de glipizide contenu dans une forme pharmaceutique osmotique monocompartiment WO2004098572A1 (fr)

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EP04731419A EP1622591A1 (fr) 2003-05-06 2004-05-06 Liberation biphasique de glipizide contenu dans une forme pharmaceutique osmotique monocompartiment

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IBPCT/IB03/01771 2003-05-06
PCT/IB2003/001771 WO2003092660A1 (fr) 2002-05-06 2003-05-06 Systeme monocompartiment d'administration de medicament a regulation osmotique
IN818DE2004 2004-04-30
IN818/DEL/2004 2004-04-30

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US7611728B2 (en) 2003-09-05 2009-11-03 Supernus Pharmaceuticals, Inc. Osmotic delivery of therapeutic compounds by solubility enhancement
CN114099451A (zh) * 2020-08-31 2022-03-01 长春海悦药业股份有限公司 一种利伐沙班片及其制备方法
CN115282124A (zh) * 2022-08-19 2022-11-04 淄博万杰制药有限公司 格列吡嗪控释片及其制备方法

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Publication number Priority date Publication date Assignee Title
WO2001047500A1 (fr) * 1999-12-23 2001-07-05 Pfizer Products Inc. Forme de dosage de medicament entraine par un hydrogel
WO2001091716A1 (fr) * 2000-05-30 2001-12-06 Add Advanced Drug Delivery Technologies Ag Systeme therapeutique par voie orale comportant du glipizide

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001047500A1 (fr) * 1999-12-23 2001-07-05 Pfizer Products Inc. Forme de dosage de medicament entraine par un hydrogel
WO2001091716A1 (fr) * 2000-05-30 2001-12-06 Add Advanced Drug Delivery Technologies Ag Systeme therapeutique par voie orale comportant du glipizide

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7611728B2 (en) 2003-09-05 2009-11-03 Supernus Pharmaceuticals, Inc. Osmotic delivery of therapeutic compounds by solubility enhancement
CN114099451A (zh) * 2020-08-31 2022-03-01 长春海悦药业股份有限公司 一种利伐沙班片及其制备方法
CN115282124A (zh) * 2022-08-19 2022-11-04 淄博万杰制药有限公司 格列吡嗪控释片及其制备方法

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