Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1999-05-26
2001-03-06
Levy, Neil S. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S465000, C424S466000, C424S474000, C424S479000, C424S486000, 57
Reexamination Certificate
active
06197336
ABSTRACT:
BACKGROUND OF THE INVENTION
1.Field of the Invention
The present invention relates to an analgesic composition useful for preparing fast dissolving tablets containing ibuprofen and arginine and the tablets made therefrom.
2.Discussion of the Background
Ibuprofen is the International common name of the compound 2-(4-isobutylphenyl)-propionic acid, which is a known drug with analgesic, as well as anti-inflammatory and antipyretic, activity of broad diffusion.
In U.S. Pat. No. 4,279,926, ibuprofen salts with basic amino acids such as arginine and lysine have been described.
In U.S. Pat. No. 4,689,218 effervescent compositions of ibuprofen containing arginine together with 20-30% by weight of bicarbonate and 25-40% by weight of sodium bitartrate have been described.
The described formulations are useful for preparing drinkable aqueous solutions.
In U.S. Pat. No. 4,834,966 non-effervescent compositions are disclosed consisting, as a base, of a ternary mixture consisting of ibuprofen, 1.1 to 1.5 mol% arginine per mole of ibuprofen and sodium bicarbonate in a weight amount between 0.25 and 0.75 times the weight of ibuprofen.
These formulations are disclosed as very suitable for the preparation of granulates quickly soluble in water.
The administration of the so obtained aqueous solutions assures a fast analgesic effect which is achieved in about ten minutes.
Sachets containing the granulate of U.S. Pat. No. 4,834,966 are on the market. In some countries, and in particular in the U.S.A., preparations in the form of a sachet are not particularly appreciated by the public, who generally prefer the use of tablets in the treatment of conditions which need an analgesic drug.
The commercially available tablets containing ibuprofen do not have a particularly fast effect because they require about 30 minutes to completely dissolve and reach the blood stream.
In order to obtain a quick dissolution of the active principle, the present inventors tried preparing tablets starting from the ibuprofen-arginine-sodium bicarbonate ternary mixture of the above mentioned U.S. Pat. No. 4,834,966.
Unfortunately, it was impossible to obtain satisfactory results because the resulting tablets were too friable and subject to fragmentation during manufacturing and packaging.
SUMMARY OF THE INVENTION
Accordingly, one object of the present invention is to provide analgesic tablets having good workability and fast dissolution so as to assure a prompt analgesic effect.
This and other objects of the invention have been satisfied by the discovery of a composition comprising ibuprofen, arginine, linear polyvinylpyrrolidone (PVP) and a reduced amount of an alkaline bicarbonate, and a tablet prepared therefrom.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention relates to an analgesic composition comprising: ibuprofen; from 1.1 to 1.5 moles of arginine per mole of ibuprofen; from 0.5 to 10% of linear PVP with respect to the weight of ibuprofen; and from 5 to 10wt% of a bicarbonate with respect to the weight of ibuprofen.
The present invention further relates to the use of the above composition to provide tablets that are fast dissolving and fast acting. The tableting composition also includes normal excipients useful for the preparation of tablets.
Preferably ibuprofen is contained in amounts of from 100 to 400 mg/tablet, more preferably in an amounts of 100, 200 mg/tablet, most preferably in an amount of 200 mg/tablet.
Arginine is contained in the present composition in an amount of from 1.1 to 1.5 moles per mole of ibuprofen, preferably from 1.1 to 1.3 moles per mole of ibuprofen and more preferably in an amount of 1.2 mole per mole of ibuprofen.
Linear PVP is preferably a PVP having an average K value, determined according to the method described in the U.S. Pharmacopoeia XXIII, of from 25 to 90, more preferably from 50 to 90, most preferably PVP K90. It is used in an amount of from 0.5 to 10 wt.% based on weight of ibuprofen, preferably in an amount of from 2 to 8 wt.% with respect to the weight of ibuprofen.
The bicarbonate can be any bicarbonate salt that is pharmaceutically acceptable, preferably sodium or potassium bicarbonate. The bicarbonate is present in an amount of from 5 to 10 wt.%, preferably from 7 to 10 wt.% with respect to the weight of ibuprofen.
Within the context of the present description the identity of the components and amounts thereof refer to the weight and identity of the starting materials used in preparing the composition. It is possible that during preparation of the composition and/or tablets, some interaction or reaction may occur between two or more components. To the extent that such interaction or reaction occurs the present invention is intended to cover such occurrences.
Normal excipients useful in the preparation of the tablets include, but are not limited to: lubricants such as magnesium stearate, sodium stearyl fumarate and sodium benzoate; anti-adherents such as talc and polyethylenglycol; glidants such as colloidal silica; diluents such as dicalcium phosphate, cellulose (for example microcrystalline cellulose) and its derivatives, carbohydrates and polyalcohols such as saccharose, xylitol and lactose; disintegrants such as crosslinked vinylic polymers (such as crosslinked PVP), derivatives of starch and of cellulose such as sodium carboxymethyl-starch and sodium croscarmelose; wetting agents such as TWEEN 80 (Trademark registered by ICI of Americas for polysorbate) and sodium lauryl sulphate.
Suitable excipients and their amounts can be readily determined by those of ordinary skill in the art according to the methods normally used in pharmaceutical technology. However, in the present invention, it is important to avoid excipients that would cause a significant decrease in tablet dissolution rate. Further, excipients must allow a good workability of the tablet.
In preparing the tablet of the present invention it is preferable to prepare a granulate with the mixture of ibuprofen, arginine and linear PVP, to mix it with the bicarbonate and the excipients, and then to compress.
When desired, the tablets can be film coated with a coating readily soluble in the gastric environment.
Suitable coatings can be prepared using conventional tablet coating compositions and methods. Preferred coatings include OPADRY II (sold by Colorcon; a mixture of hydroxypropyl methyl cellulose, pigments and a plasticizer), EUDRAGIT (sold by Rohm Pharma; a methacrylic acid ester polymer) and a combination of OPADRY II with saccharose.
The granulate can be prepared by direct granulation of the three components (ibuprofen, arginine and linear PVP) in the desired amounts or, after a first granulation of arginine with melted ibuprofen, by granulating a second time with linear PVP.
Both granulates obtained according to the above described methods are then screened, dried, combined with bicarbonate and any selected excipient(s) in the desired amounts and compressed in suitable molds for obtaining the desired tablets which can then be film coated, if desired.
In addition to good handling and workability, the tablets of the present invention provide complete dissolution of the active ingredient in about 10 minutes or less. Consequently the release is faster with respect to the commercially available ibuprofen based analgesic tablets (see example 5 below).
Generally, linear PVP is considered a binder at the amounts used in the present invention, and would be thus expected to inhibit dissolution or have little or no effect on dissolution. While Login et al, U.S. Pat. No. 5,262,171, discloses the use of non-crosslinked PVP in tablets to provide improved drug dissolution rate, the best dissolution seen is in acetaminophen tablets containing 1-2% of PVP by weight is 30-40% dissolution within 60 minutes. This is not an improvement when one considers the dissolution of ibuprofen tablets which normally only takes about 30 minutes. The present inventors have found that use of PVP in the amounts of the present invention in an ibuprofen tablet provides suprisingly improved dissolution of ibuprofen table
Castegini Franco
Di Toro Mauro
Grassano Alessandro
Marchiorri Maurizio
Levy Neil S.
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
Zambon Group S.p.A.
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