Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
2001-01-18
2002-12-24
Dees, Jose′ G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S401000, C424S484000, C424S488000
Reexamination Certificate
active
06497899
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to highly porous, non-friable, rapidly disintegrating, fast-dissolving solid dosage forms that are produced from pharmaceutically acceptable steam-extruded polymers. The solid dosage forms of the invention dissolve in the mouth and are particularly useful for subjects that require or desire oral medication but have difficulty swallowing standard oral dosage forms such as tablets or in subjects suffering from emesis or who require or desire a faster acting treatment, or a more palatable dosage form. The solid dosage forms of the invention are also useful as vaginal and rectal suppositories.
BACKGROUND OF THE INVENTION
The present invention is a rapidly disintegrating, fast-dissolving dosage form that is broadly applicable for the pediatric, geriatric, HIV-oncology, migraine-CNS, anti-emetic, and animal health therapies. The presently described dosage forms utilize a steam extruded polymeric matrix. Rapidly disintegrating pharmaceutical dosage forms that utilize a non-steam extruded matrix have been described in U.S. Pat. No. 4,371,516 and non-steam extruded, rapidly disintegrating materials related to pharmaceutical dosage forms is described in U.S. Pat. No. 4,305,502.
Steam extruded starch compositions for use in packaging and the methods of producing such compositions have been described in U.S. Pat. Nos. 4,072,535; 4,863,655; 5,035,930; 5,043,196; 5, 286,769; 5,405,564 and 5,849,233.
SUMMARY OF THE INVENTION
This invention relates to rapidly disintegrating, fast-dissolving dosage forms for the delivery of a medicament that are produced from steam extruded pharmaceutically compatible polymers.
A second aspect of the invention is a steam extruded rapidly disintegrating, fast-dissolving dosage form produced from high amylose starch, i.e., one comprising at least about 45% by weight of amylose which is optionally derivatized and optionally comprising about 2% or more by weight of salt.
A third aspect of the invention is a steam extruded rapidly disintegrating, fast-dissolving dosage form produced from gelatin, particularly gelatin that is hydrolyzed, or other polymeric materials such as dextran, dextrin, and alginates (e.g. sodium alginate) or mixtures of polymeric materials with each other or with other carrier materials such as polyvinyl alcohol, polyvinylpyrrolidine or acacia.
A fourth aspect of the invention is a rapidly disintegrating, fast-dissolving dosage form having a uniform, closed cell structure with low density and low friability and good resilience, compressibility, disintegration and dissolution properties. The bulk density of the rapidly disintegrating, fast-dissolving dosage form will be from about 2 to about 80 mg/cc, and preferably from about 2 to about 50 mg/cc; and more preferably from about 2 to about 9 mg/cc excluding medicament and other carriers, vehicles or diluents. The bulk density of the dosage form containing drug will be from about 2 to about 550 mg/cc; and more preferably from about 2 to about 200 mg/cc.
A fifth aspect of the invention is a steam extruded rapidly disintegrating, fast-dissolving dosage form in a shaped configuration for use as a vaginal or rectal suppository.
A sixth aspect of the invention is a method of producing rapidly disintegrating, fast-dissolving dosage forms that involves mixing a medicament with the polymeric material and other optional carriers, vehicles or diluents and steam extruding the medicament-containing polymeric material into an expanded product for forming the dosage form. The medicament-containing extruded polymeric material may be formed into the final dosage form during the steam extrusion process or may undergo subsequent shaping steps such as stamping, cutting, molding or thermoforming.
A seventh aspect of the invention is a method of producing rapidly disintegrating, fast-dissolving dosage forms by steam extruding pharmaceutically acceptable polymeric materials and later loading a medicament into the extrudate. The loading of medicament can take place prior to or subsequent to the final forming or shaping steps such as stamping, cutting, molding or thermoforming.
An eighth aspect of the invention is a method of administering a medicament to a mammal in need thereof by administering a solid dosage form comprising a steam extruded pharmaceutically acceptable polymer and a medicament to the mammal.
A ninth aspect of the invention provides for kits for use by a consumer that require or desire a rapidly disintegrating, fast-dissolving dosage form. The kits comprise a solid dosage form comprising a steam-extruded polymer and a medicament and further comprise a container for holding the dosage form and instructions for the using the dosage form.
A tenth aspect of the invention is a rapidly disintegrating, fast-dissolving veterinary dosage form that is taste-masked so that consumption of the dosage form is desired by an animal thus allowing easy administration of a medicament.
An eleventh aspect of the invention is a rapidly disintegrating, fast-dissolving dosage form containing a drug compound wherein a major portion of the drug is amorphous. As used herein, the term “a major portion” of the drug means that at least 60% of the drug in the dispersion is in the amorphous form, rather than the crystalline form. Preferably, when amorphous drugs are used, the drug added to the rapidly disintegrating, fast-dissolving dosage form is substantially amorphous. As used herein, “substantially amorphous” means that the amount of the drug in crystalline form does not exceed 25% as measured by powder X-ray diffraction analysis or by differential scanning calorimetry or by any other standard quantitative measurement. More preferably, when amorphous drugs are used, the drug added to the rapidly disintegrating, fast-dissolving dosage form is essentially amorphous. As used herein, “essentially amorphous” means that the amount of the drug in crystalline form does not exceed 10% as measured by the methods previously described.
DETAILED DESCRIPTION OF THE INVENTION
The starting materials useful for the rapidly disintegrating, fast-dissolving dosage form must be pharmaceutically acceptable polymeric materials. The polymeric materials used to produce the dosage forms of the invention are highly water-soluble and form a gel phase with hot water under pressure. After extrusion the water rapidly vaporizes leaving a highly porous solid foam. This process is known as “steam extrusion”.
A “subject” is an animal including a human that is treatable with the compositions, methods and kits of the present invention. The term “subject” or “subjects” is intended to refer to both the male and female gender unless one gender is specifically indicated.
“Solid dosage form” is defined as a rapidly-disintegrating, fast-dissolving dosage form that can be in the form of granules, pellets, sheets, tablets, capsules, shaped forms and the like.
Amorphous drugs may be used with the rapidly disintegrating, fast-dissolving dosage form to increase the rate of dissolution over crystalline forms of the drugs.
Pharmaceutically acceptable polymers disclosed herein include all manmade and natural polymers and polymeric materials that are compatible with the processes. Non-limiting examples of polymers include gelatin, particularly gelatin that is hydrolyzed, e.g. by heating in water. For example, gelatin may be partially hydrolyzed by heating a solution of the gelatin in water in an autoclave at about 120° C. for up to 2 hours. Other polymeric materials may include dextran, dextrin, alginates (i.e., sodium alginate), hydroxypropyl methylcellulose (HPMC) or mixtures of polymeric materials with each other or with other carrier materials such as polyvinyl alcohol, polyvinylpyrrolidine or acacia. A preferred polymeric material of the invention is high amylose starch, i.e., one containing at least 45% by weight of amylose. The starch used is unlike common starch since it is resilient, not brittle. A typical starch useful for making these materials is produced by National Starch and Chemical Company (Belle Mead, N.J.) and sold
Thombre Avinash G.
Wigman Larry S.
Benson Gregg C.
Dees Jose′ G.
George Konata M.
Goddard Carl J.
Pfizer Inc.
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