Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Matrices
Reexamination Certificate
1999-03-02
2002-12-03
Webman, Edward J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Matrices
C514S953000
Reexamination Certificate
active
06488963
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the field of poly(ethylene oxide) (PEO) based hot-melt extrudable pharmaceutical formulations that are not film-like preparations. The invention relates more specifically to non-film formulations which have been prepared by hot-melt extrusion of mixtures containing high molecular weight PEO and a therapeutic compound. The present formulations cited relate to the field of non-film controlled-release drug delivery preparations, as they provide preparations useful for providing controlled drug delivery.
BACKGROUND OF THE INVENTION
Hot-melt extrusion as a method for producing polymer-based sustained-release pharmaceutical formulations, such as with derivatized cellulose, poly(methacrylate) derivative, poly(ethylene-co-vinyl acetate), poly(ethylene), poly(vinyl acetate-co-methacrylic acid), epoxy resins and caprolactones is known. These methods do not teach the use of poly(ethylene oxide). Hot-melt extrusion as a method for producing poly(ethylene glycol) based pharmaceutical formulations comprising an “erosion rate modifier” has been disclosed. These particular compositions have, been described as further containing trace amounts of high molecular weight PEO, and the hot-melt extrusion process used to prepare them requires several steps. These particular compositions are also based upon a low melting matrix drug delivery system, and are predominantly for transdermal rather than oral administration.
Alderman et al. (EP 0177893 A2) relates to a thermoformable sustained release matrix for the prolonged release of an active organic material of a thermoplastic water-soluble gel having a water-soluble hydroxypropylmethylcellulose a plasticizer and an active organic material dispersed in said gel. The plasticizer may be a low molecular weight poly(ethylene glycol).
Mooney et al. (EP 0598606 A1) relates to compositions of a thermoplastic water-soluble polymer; a water-soluble polymer derived from a carboxylic acid or a pharmaceutically acceptable salt thereof; and a plasticizer. The thermoplastic water-soluble polymer may be poly(ethylene oxide), and the compositions can be prepared as hot-melts.
These various methods require several components to achieve a desired controlled release profile. Various technical disadvantages exist for each of them that creates a significant potential for loss in pharmacological activity of the included therapeutic agent.
Hot-melt extrusion processes in the art have generally required elevated temperatures. Elevated temperatures in processing have been recognized by those in the pharmaceutical formulation arts to cause decomposition of the therapeutic agent or polymer matrix. The process of hot-melt extrusion of a therapeutic agent and a high molecular weight polymer PEO has been primarily confined to the preparation of film-like preparations.
Although various hot-melt extrusion pharmaceutical formulations and methods for making them are known, development of simple formulations for drug delivery and methods for producing them remains a problem in the pharmaceutical industry.
There continues to exist a need in the art to develop controlled-release pharmaceutical formulations, as well as improved, more efficient methods for their preparation.
SUMMARY OF THE INVENTION
In one aspect of the present invention comprises a hot-melt extrudable controlled-release pharmaceutical formulation. This formulation in some embodiments is further described as comprising an effective amount of a therapeutic compound and a high molecular weight poly(ethylene oxide) homopolymer.
It is an object of the present invention to provide a hot-melt extrudable controlled-release pharmaceutical formulation comprising high molecular weight poly(ethylene oxide) and an effective amount of a therapeutic compound.
It is another object of the present invention to provide a hot-melt extrudable controlled-release pharmaceutical formulation comprising high molecular weight poly(ethylene oxide), an effective amount of a therapeutic compound and a plasticizer. By way of example, the plasticizer may comprise poly(ethylene glycol).
It is contemplated and within the scope of the present invention that the pharmaceutical formulation may be administered to a subject by any of a variety of methods known to the artisan. In some embodiments, the formulations are designed to be particularly well suited for oral delivery.
It is also contemplated and within the scope of the present invention that the pharmaceutical formulation may comprise other components.
The methods provided on some aspects of the present invention may comprise a single step or multiple steps for preparing the pharmaceutical formulation.
It is also contemplated that the particular combinations of therapeutic compound and PEO (of given molecular weight) will result in various formulations, each possessing a particular combination of properties. Some combinations may be better suited for particular types or classes of therapeutic compounds while another combination may be better suited for other types or classes of therapeutic compounds. Methods for the selection of a particular therapeutic compound/PEO (of a given molecular weight) combination are also provided as part of the present invention.
Some embodiments of the invention comprise a plasticizer. The particular combinations of therapeutic compound/plasticizer/PEO (of given molecular weight) may be selected to provide a desired combination of physical properties. Some particular combination of these ingredients may accordingly be better suited for a particular therapeutic compound while another combination may be better suited for a different therapeutic compound. Methods for the selection of a particular therapeutic compound/plasticizer/ PEO (of a given molecular weight) combination are also disclosed as part of the present invention.
Another aspect of the invention provides a process for preparing a controlled-release pharmaceutical formulation comprising a therapeutic compound and a high molecular weight poly(ethylene oxide) homopolymer. The process in some embodiments comprises hot-melt extruding a pharmaceutical formulation. The pharmaceutical formulation comprises a therapeutic compound and a high molecular weight poly(ethylene oxide) homopolymer.
Other embodiments of the present controlled-release pharmaceutical formulations comprise a therapeutic compound and a high molecular weight poly(ethylene oxide) homopolymer, where the formulation is prepared by hot-melt extruding a mixture of its components.
In some embodiments, the pharmaceutical formulations of the invention may contain more than one therapeutic compound, as well as other non-therapeutic compound components. The pharmaceutical formulations may be formulated to provide sustained, extended, controlled, timed or other equivalent release dosage forms.
Other features, advantages and embodiments of the invention will be apparent to those skilled in the art from the following description, accompanying data and appended claims.
As used in the description of the present invention, the term “effective amount” is defined as an amount or dose sufficient to elicit a physiological response in vitro or in vivo
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McGinity James W.
Zhang Feng
Flores Edwin S.
Gardere Wynne & Sewell LLP
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Warren, Jr. Sanford E.
Webman Edward J.
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