Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
2001-05-01
2004-01-13
Qazi, Sabiha (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S469000, C424S468000, C424S484000, C424S489000, C424S450000, C424S456000, C424S475000, C424S479000, C424S480000, C424S474000, C424S472000
Reexamination Certificate
active
06676966
ABSTRACT:
RELATED APPLICATIONS
This application claims priority to U.S. application Ser. No. 60/202,768 filed May 9, 2000.
FIELD OF THE INVENTION
The present invention relates mainly to a formulation composition and method of producing extended release dosage form containing metformin hydrochloride or a pharmaceutically acceptable salt thereof.
BACKGROUND OF THE INVENTION
Metformin hydrochloride is an oral antihyperglycemic drug used in the management of non-insulin-dependent diabetes mellitus (type 2 diabetes). Metformin hydrochloride, as monotherapy, is indicated as an adjunct to diet to lower blood glucose in patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed on diet alone. Recommended dosing schedule for metformin involves dose escalation with each dose given with meals. This allows metformin to be better tolerated as gastrointestinal symptoms usually associated with metformin therapy may be minimized. However it has been reported in the Physician Desk Reference electronic library release 2000.1 that, food decreases the extent and slightly delays the absorption of metformin, as shown by approximately a 40% lower peak concentration and 25% lower AUC in plasma and a 35 minute prolongation of time to peak plasma concentration following administration of a single 850 mg immediate release tablet of metformin with food, compared to the same tablet strength administered without food. Metformin is marketed as an immediate release formulation and is administered several times a day a situation that has raised concerns regarding patient compliance.
Limited research work has been done to fabricate controlled release metformin hydrochloride and no successful work has been reported on an extended release metformin composition or dosage form.
A pharmaceutical preparation containing metformin and a process for producing it is disclosed in U.S. Pat. No. 5,955,106 in which the pharmaceutical compositions contain metformin as an active substance and a hydrocolloid-formning agent as a retardant. The invention also concerns a process in which the active substance and retarding agent or a portion thereof are granulated with an aqueous solvent optionally containing a binder and where appropriate the other portion of the retardant or other standard pharmaceutical auxiliaries are admixed with the granulate.
U.S. Pat. No. 5,594,091 discloses a matrix for sustained-release preparation comprising an ester formed at a terminal carboxyl group of a straight-chain polyester which essentially consists of an alpha-hydroxymonocarboxylic acid.
U.S. Pat. No. 5,576,306 discloses pharmaceutical compositions and uses of water-soluble, high-viscosity grade cellulose ethers which may be in the form of a prehydrated ingestible composition, such as a gelatin, or a comestible, such as a cookie.
U.S. Pat. No. 5,575,987 discloses a method of producing sustained-release microcapsules from an WIO emulsion comprising an inner aqueous phase containing said metformin and an external oil phase containing a biodegradable polymer.
U.S. Pat. No. 5,540,665 discloses a gas driven dispensing device and gas generating engine comprising (a) a solid composition comprising an acidic compound or a basic compound, or a combination thereof, and (b) a means for maintaining substantially constant the surface area of the solid composition exposed to a reservoir fluid comprising water, or water and an acidic compound, or water and a basic compound, wherein in operation, the solid composition is exposed to the reservoir fluid which dissolves the solid composition and causes it to generate a gas, the gas being a driving fluid to dispense a beneficial agent such as metformin.
U.S. Pat. No. 5,055,306 discloses a granular sustained-release formulation consisting of a pharmacologically active substance presented in the form of a tablet, said tablet comprising sufficient granules to provide a predetermined dose or number of doses of the pharmacologically active substance and effervescent or water-dispersible ingredients, each of said granules having a diameter of preferably between 0.5 and 2.5 mm and comprising: a) a core comprising one or more pharmacologically active substances and preferably one or more excipients; and b) a coating covering substantially the whole surface of the core and comprising 100 parts of a water insoluble but water swellable acrylic polymer and from 20 to 70 parts of a water soluble hydroxylated cellulose derivative, the weight of the coating being from 2 to 25% of the weight of the core. A method for preparing this effervescent of water-dispersible tablet formulation is also provided.
U.S. Pat. No. 4,834,985 discloses a solid controlled release pharmaceutical composition comprising an active ingredient incorporated in a matrix comprising a first substance selected from a water soluble polydextrose and a water soluble cyclodextrin and a second substance selected from a C
12
-C
36
fatty alcohol and a polyalkylene glycol. Preferably the first substance is a cyclodextrin, especially a beta-cyclodextrin, while the second substance is a C
14
-C
22
fatty alcohol, especially stearyl alcohol, cetyl alcohol, cetostearyl alcohol or myristyl alcohol. The matrix may also contain a cellulose ether, especially a hydroxyalkylcellulose or a carboxyalkylcellulose.
U.S. Pat. No. 4,351,825 discloses a process for the preparation of matrix-type tablets with retarded liberation of the active agent. In the granulation process, polymethacrylate plastics insoluble in neutral or slightly acid water either as dissolved in an organic solvent or as a water dispersion are used as the retarding matrix substance. Before the tablets are compressed, an ester of a large-molecule fatty acid or a product obtained from same by means of hydrogenation is mixed into the grain mix in order to adjust the rate of liberation of the active agent.
PCT/US99/19978 discloses a controlled release pharmaceutical tablet containing antihyperglycemic drug and a hypoglycemic drug comprising a core containing the antihyperglycemic drug, a semipermeable coating membrane surrounding the core and at least one passageway in the membrane to allow the drugs to be released from the core.
The problem with current controlled release formulations of metformin is that the extent of metformin release or bioavailability is not optimal or does not provide sufficient coverage over an extended period of time such as for 12 hours and a 24 hour period. Furthermore, for coated tablets the choice of coating polymer(s) makes large scale or commercial production of consistent and reproducible batches difficult if not impossible. The manufacturing process for these formulations involves long process times and a large number of process steps, requiring qualification, cleaning and validation. Stability problems during manufacture and storage may be an issue with current controlled systems especially for the delivery of large doses of metformin.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an extended and controlled release composition and formulation of metformin hydrochloride that can provide detectable blood levels of the said agent over 12 hours and or over 24 hours when given to humans or animals thus allowing for twice and/or once daily administration.
It is also an object of the present invention to provide an extended and controlled release composition and formulation of metformin hydrochloride that does not employ a matrix-type tablet or contain an expandable, gelling, swellable hydrocolloid polymer as a retardant agent.
It is a further object of the present invention to provide an extended and controlled release composition and formulation of metformin hydrochloride that does not employ sustained-release microcapsules.
It is a further object of the present invention to provide an extended and controlled release composition and formulation of metformin hydrochloride that does not employ a gas driven dispensing device and gas generating engine to dispense a beneficial agent such as metformin.
It is also a further object of the present in
Odidi Amina
Odidi Isa
Intellipharmaceutics Corp.
Qazi Sabiha
Sim & McBurney
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