Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Food or edible as carrier for pharmaceutical
Reexamination Certificate
1999-05-04
2003-09-30
Webman, Edward J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Food or edible as carrier for pharmaceutical
C424S439000, C424S469000, C424S484000, C514S784000, C514S974000
Reexamination Certificate
active
06627214
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to ibuprofen compositions, more specifically to ibuprofen compositions with reduced throat burn characteristics.
Many flavors and sweeteners have been added to medication in order to make them more palatable and to mask the unpleasant taste and aftertaste which is common with many medications. Certain medicinal ingredients, in addition to having an unpleasant taste, create a burning or scratching sensation in the throat when swallowed. Flavors and sweeteners do little to overcome this throat burning sensation. Despite numerous efforts to find an effective means to eliminate this burn, there is a continuing need for a method to effectively eliminate the burning sensation with medications, preferably the burn can be reduced to a level such that a chewable composition can be provided.
Ibuprofen is a well known medication which possesses an unpalatable burning sensation in the mouth and throat after ingestion.
Japanese Patent Application 9 (1997)-2949 assigned to American Home Products attempts to eliminate the unpalatable aftertaste by providing only one enantiomer. The patent application discloses the separation of ibuprofen from its racemic mixture to form an orally administered drug composition which contains only the S(+)-ibuprofen and essentially no R(+)-ibuprofen. While this approach may provide a more palatable form of ibuprofen the separation and isolation of the enantiomers are difficult.
U.S. Pat. No. 5,320,855 discloses a method of masking the taste of ibuprofen by granulating with polyvinylpyrrolidone, sodium starch glycolate and sodium lauryl sulfate and coating the resulting granules with hydroxyethyl cellulose or a mixture of hydroxyethyl cellulose and hydroxypropyl methylcellulose. While resulting in a significant taste improvement, this method has been found not to completely eliminate the “throat burn” associated with ibuprofen in chewable dosage forms.
U.S. Pat. No. 4,762,702 discloses ibuprofen particles enveloped by a coating of hydrocolloid film, containing fumaric acid. The hydrocolloid performs the function of connecting the water insoluble ibuprofen particles to the sparingly soluble fumaric acid for use in a powder for reconstitution in liquid. The preferred hydrocolloid composition comprises xantham gum and/or maltodextrin. The amount of the fumaric acid is 10% of the amount of the ibuprofen, and from about 0.46% to about 0.64% of the total formula. The patent discloses this method as reducing the tendency of ibuprofen to irritate the esophagus and gastrointestinal tract.
Despite the disclosures of the above patents and application, a simpler and less costly method for providing a tastemasked ibuprofen composition with reduced throat burn is still desired.
SUMMARY OF THE INVENTION
The present invention provides racemic mixtures of propionic acid derivatives with fumaric acid in an amount from about 50 to about 150 percent of the amount of the propionic acid derivative. Typically the level of fumaric acid is from about 5% to about 60% by weight of the total dosage form. We have found that these relatively high levels of fumaric acid do not impart an unacceptably high sourness to the product, as would similar levels of other pharmaceutically acceptable acids. The present invention provides fumaric acid sufficient to reduce the burn sensation of propionic acid derivatives without the requirement of connecting the fumaric acid particles to the propionic acid derivative by incorporation in a hydrocolloid coating. Additionally, the present invention provides fumaric acid sufficient to reduce the burn sensation of propionic acid derivatives in compositions that are substantially free of a hydrocolloid agent. In a preferred embodiment the propionic. acid derivative/fumaric composition is provided in a chewable form.
A method for inhibiting the burn sensation of racemic mixtures of propionic acid derivatives by providing an effective amount of fumaric acid is also provided.
DETAILED DESCRIPTION OF THE INVENTION
Propionic acid derivatives are a well known class of analgesic compounds. As used herein propionic acid derivatives are understood to include, but are not limited to, ibuprofen, naproxen, benoxaprofen, naproxen sodium, flurbiprofen, fenoprofen, fenbuprofen, ketoprofen, indoprofen, pirprofen, carpofen, oxaprofen, pranoprofen, microprofen, tioxaprofen, suproprofen, alminoprofen, tiaprofenic acid, fluprofen and bucloxic acid. The structural formula is set forth in U.S. Pat. No. 4,923,898, hereby incorporated by reference. Propionic acid derivatives as defined herein are defined as pharmaceutically acceptable analgesics
on-steroidal anti-inflammatory drugs having a free —CH(CH
3
)COOH or —CH
2
CH
2
COOH or a pharmaceutically acceptable salt group, such as —CH(CH
3
)COO—Na+ or CH
2
CH
2
COO—Na+, which are typically attached directly or via a carbonyl functionality to an aromatic ring system.
Propionic acid derivatives are typically administered on a daily basis, with the daily dose ranging from about 50 to about 2000 milligrams, preferably from about 100 to 1600 and most preferably from about 200 to about 1200 milligrams.
Ibuprofen is a widely used, well known non-steroidal anti-inflammatory propionic acid derivative. Ibuprofen is chemically known as 2-(4-isobutylphenyl)-propionic acid. As used herein ibuprofen is understood to include 2-(4-isobutylphenyl)propionic acid as well as the pharmaceutically acceptable salts. Suitable ibuprofen salts include arginine, lysine, histidine, as well as other salts described in U.S. Pat. No. 4,279,926, 4,873,231, 5,424,075 and 5,510,385, the contents of which are incorporated by reference.
Fumaric acid is a widely available pharmaceutically acceptable acid. The concentration of fumaric acid present to inhibit the burn of propionic acid derivative will vary on the amount of burn reduction desired. Generally the level of fumaric acid is from about 50 to about 150 weight percent of the propionic acid derivative dosage. Typically the level of fumaric acid is from about 60 to about 100 percent by weight of the level of propionic acid derivative and most preferably from about 70 to about 90 percent by weight of the level of propionic acid derivative dosage. Typically the level of fumaric acid is from about 5% to about 60% by weight of the total dosage form. In a preferred embodiment, the fumaric acid is from about 7% to about 13% by weight of the final dosage form.
Fumaric acid has commonly been used as a pharmaceutical excipient, as have other pharmaceutically acceptable acids, such as citric, malic, and tartaric acids, generally at levels less than 1% by weight of the total formula. Most pharmaceutically acceptable acids are well known in the art to impart an objectionably high sour taste at levels in excess of 5 weight percent of the total formula.
Contrary to the teaching of prior disclosures, the present invention does not require the incorporation of a hydrocolloid material in contact with fumaric acid in the coating in order to be effective. Inclusion of hydrocolloid materials in the present invention is optional.
The present invention allows for a hydrocolloid to coat the racemic mixture of the propionic acid derivative, but if a hydrocolloid coating is provided on the propioinic acid derivative, no fumaric acid is to be incorporated in the hydrocolloid film. Instead, the fumaric acid is provided in the dosage form with the other excipients, such as flavors, sweeteners and the like.
In a preferred embodiment, the present invention is substantially free of hydrocolloids, that is understood to be less than about 7 weight percent of the final dosage form. In a highly preferred embodiment, the present invention contains a coating around the granulated racemic mixture of the propionic acid derivative which contains less than about 5 weight percent hydrocolloid, based on the total weight of the tablet, preferably less than about 4 weight percent and in some circumstances the coating does not contain any hydrocolloid.
Suitable hydrocolloid coatings
Bunick Frank J.
Lin Feng
Mc-Neil-PPC, Inc.
Webman Edward J.
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