Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1994-03-17
2003-12-23
Webman, Edward J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S078100, C424S468000, C424S502000, C424S436000, C424S457000, C424S423000, C514S357000
Reexamination Certificate
active
06667058
ABSTRACT:
The present invention relates to pharmaceutical dosage forms containing flupirtine with controlled release of the 5 active ingredient.
BACKGROUND OF THE INVENTION
Flupirtine is a pharmaceutically active substance having the formula:
Flupirtine is useful as an analgesic. However, it sometimes causes a sedative side-effect.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a solid dosage form of the pharmaceutically active substance flupirtine in which the sedative side effects of the flupirtine are largely or totally suppressed. A further object of the invention is to provide a solid dosage form of flupirtine which is useful for patients who require therapy with an analgesic which formulation does not have to be taken as frequently as in the case of conventional formulations.
The invention is particularly advantageous for patients with severe pain, e.g. tumor patients, who find the less frequent administration of drugs as well as longer duration of action to be advantageous, especially in the case of night pain. A further advantage of the invention is that the amount of active substance to be used daily takes strain off the body, especially the liver.
These and other objects are achieved by means of a pharmaceutical dosage form or pharmaceutical composition comprising or consisting essentially of flupirtine as the active substance and containing, in addition to customary adjuvants and additives, a delayed-action or controlled-release component. The composition is formulated so that the active substance flupirtine or its pharmaceutically-acceptable salts is/are released in a controlled manner and is present in an amount of 1 part by weight flupirtine, relative to the base, per 0.001 to 20 parts by weight delayed-action or controlled-release component and that the release is from 5 to 300 mg, e.g. 10 to 100 mg or also 20 to 60 mg flupirtine/hour. The pharmaceutical dosage unit may be formulated for oral administration and contain 50 to 600 mg flupirtine active substance, for parenteral use and contain 50 to 500 mg flupirtine active substance or for dermal use and contain 5 to 5000 mg flupirtine active substance.
This pharmaceutical composition with controlled release of the active substance can also be combined with an additional amount of flupirtine or of one of its pharmaceutically acceptable salts, which additional amount is formulated without the addition of delayed-action component and is rapidly released, that is, within 10 to 20 minutes. This additional amount can provide an initial phase of treatment assuring a rapid commencement of the action of the dosage form. In this manner, such a form of administration can bring about a rapidly commencing and long-lasting action, which is desirable for pain-killers. The amount of the initial phase flupirtine, i.e., without controlled-release component, in proportion to the amount of flupirtine which is released in a controlled manner, is in this instance 2:1 to 1:9 (amounts by weight in each instance, based on the amount of flupirtine base).
As indicated above, the flupirtine can be present as the free base or as a salt. Suitable salts are e.g. chloride, maleate, D-gluconate. If the flupirtine is present in the form of a salt, the amount of flupirtine, indicated above and calculated as the base, is increased corresponding to the greater molecular weight of the salt. The amounts in this description in the “flupirtine” indication always refers to the base and should be converted, upon the presence of a salt, in accordance with the increased molecular weight.
A further object of the invention is to provide a method for preparing a pharmaceutical composition of flupirtine which achieves controlled release of active substance, the method comprising introducing the active substance into customary adjuvants and additives and a delayed-action or controlled-release component which method is characterized in that flupirtine or its physiologically compatible salts are used in a ratio of 1 part by weight flupirtine, calculated as the base, per 0.001 to 20 parts by weight delayed-action component as active substance to be released in a controlled manner and that the release rate is adjusted to the range of 5 to 300 mg flupirtine/hour.
If the active substance flupirtine is placed in a form of administration which releases the active substance over a fairly long time period (and therewith brings about a “delaying” of the effect of the active substance), the side effect of tiredness is no longer detected in persons treated with this form of administration.
The subject matter of the invention is therefore constituted by solid forms of administration with a controlled release of the active substance flupirtine or pharmaceutically salts of flupirtine. Further subject matter of the invention comprises a method of preparing a dosage form which provides controlled release of the active substance flupirtine or of pharmaceutically acceptable salts of flupirtine.
The determination of the release rate of flupirtine within the limits indicated on above is carried out in an aqueous solution with pH 1 or 6.8. The pH'es are adjusted by means of the addition of acid or by the addition of a customary buffer, e.g. a phosphate buffer. The method is described in the USP XXII, Jan. 1, 1990, pp. 1578-1579.
The following are potential examples of forms of administration: Tablets, film tablets, hard-gelatin capsules, soft-gelatin capsules, pellets, granulates, coated tablets, suppositories, microcapsules, aqueous or oily suspensions, oily solutions.
The controlled-release compositions of the invention can be obtained as follows:
1. By binding flupirtine to physiologically compatible cation exchangers. The following can be used, for example, as such cation exchangers: Acrylic and methacrylic resins with exchangeable proton, acid groups: COO, e.g. Amberlite® IRP-64 polystyrene resins with exchangeable Na, acid groups: SO
3
, e.g. Amberlite® IRP-69.
The ion exchangers are acidic ion exchangers. The maximum ratio of flupirtine : ion exchanger is approximately 1:1 and the minimum ratio is approximately 1 part by eight active substance per 800 parts ion exchange resin. It is preferable to use 1 to 400 parts by weight ion exchanger, quite especially 1 to 100 parts by weight ion exchanger per 1 part by weight active substance.
The binding of the flupirtine takes place by allowing a solution of flupirtine to run through a bed of the ion exchanger in a column or the ion exchanger is suspended in a solution of flupirtine, filtered off after agitation and washed. The charged ion exchanger is dried at temperatures of up to approximately 50° C. The charged ion-exchanger particles are also preferably provided with a casing, as is described e.g. in U.S. Pat. No. 4,221,776. An advantage of the additional casing resides in the fact that the release rate of the active substance can be varied and influenced by the selection of the casing material. The drying of the charged ion-exchanger particles provided with casing can take place with warm air of 70° C. to 90° C.
The charged ion-exchanger particles can be filled into hard-gelatin capsules or be prepared with the aid of water and thickening agents, flavoring substances, stabilizing substances and preservatives as a suspension as form of administration.
2. The encasing of active-substance particles, granulate- or pellet grains or of tablets containing flupirtine with coatings of the following substances, which casing substances can also be used in a mixture: Hydroxypropylmethyl cellulose phthalate or -acetate succinate; cellulose-, starch- as well as polyvinyl acetate phthalate; carboxymethyl cellulose; polyvinyl acetate; methyl cellulose phthalate, methyl cellulose succinate, methyl cellulose phthalate succinate as well as methyl cellulose phthalicacid semi-ester; zein; ethyl cellulose as well as ethyl cellulose succinate; shellac; gluten; ethylcarboxyethyl cellulose; ethacrylate-maleic-acid anhydride copolymer; maleic-acid anhydride vinylmethyl ether copolymer; styrene-maleic-acid copolymers; 2-ethyl-hexyl-
Engel Jürgen
Goede Joachim
Hettche Helmut
Lobisch Michael
Momberger Helmut
Hobbs Ann S.
Vanable LLP
Viatris GmbH & Co. KG
Webman Edward J.
LandOfFree
Oral forms of administration containing solid flupirtine... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Oral forms of administration containing solid flupirtine..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Oral forms of administration containing solid flupirtine... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3183080