Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Utility Patent
1998-05-07
2001-01-02
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S464000, C424S489000, C514S770000, C514S772100, C514S772300, C514S777000, C514S781000, C514S778000, C514S782000
Utility Patent
active
06168805
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to processes for preparation of pharmaceutical compositions, the resultant compositions, and their use. Specifically, the present invention relates to pharmaceutical formulations of paroxetine, processes for the preparation of such formulations, pharmaceutical compositions containing the same and their use thereof in therapy.
2. Description of the Prior Art
The compound (−)-trans-4-((4′-fluorophenyl)3-(3′4′-methylenedioxyphenoxymethyl)-piperidine, commonly known as paroxetine, is a viscous oil and poorly water soluble drug which has been widely used pharmaceutical compositions, especially for depression.
U.S. Pat. No. 4,721,723 discloses crystalline paroxetine hydrochloride hemihydrate as a novel material with better handling properties than anhydrous paroxetine hydrochloride, a hygroscopic solid with poor handling properties.
Because U.S. Pat. No. 4,721,723 is based on the alleged better handling properties of crystalline paroxetine hydrochloride hemihydrate than anhydrous paroxetine hydrochloride, “a hygroscopic solid with poor handling properties” according to said U.S. patent, it has become an objective to provide anhydrous paroxetine which is not hygroscopic and has excellent handling properties and can be readily formulated into a commercial dosage form. Another object is to provide a process which eliminates the additional steps necesssary according to said U.S. patent to manufacture crystalline material, and thereby to reduce the manufacturing steps versus the steps required to produce the crystalline form.
International Patent Publication WO 96/24595 discloses paroxetine hydrochloride solvates other than the propan-2-ol solvate as precursors in the preparation of paroxetine hydrochloride substantially free of bound organic solvent. WO 96/24595 also discloses four novel paroxetine hydrochloride anhydrates substantially free of bound solvent.
International Patent Application WO 97/03670 published Feb. 6, 1997 discloses controlled release paroxetine formulation comprising “a reaction complex formed by the interaction of (1) a calcium polycarbophil component which is a water-swellable, but water insoluble, fibrous cross-linked carboxy-functional polymer, said polymer containing (a) a plurality of repeating units of which at least about 80% contain at least one carboxyl functionality, and (b) about 0.05 to about 1.5% cross-linking agent substantially free from polyalkenyl polyether, said percentages being based upon the weights of unpolymerized repeating unit and cross-linking agent, respectively, with (2) water, in the presence of an active agent selected from the group consisting of SSRI's such as paroxetine . . . a further particular aspect [of the WO 97/03670 invention] provides a system for the controlled release of an active substance which is an SSRI such as paroxetine, comprising (a) a deposit-core comprising an effective amount of the active substance having defined geometric form, and (b) a support-platform applied to said deposit-core, wherein said deposit-core contains at least the active substance, and at least one member selected from the group consisting of (1) a polymeric member which swells on contact with water or aqueous liquids and a gellable polymeric material . . . and (2) a single polymeric material having both swelling and gelling properties, and wherein the support platform is an elastic support, applied to said deposit-core so that it partially covers the surface of the deposit-core and is slowly soluble and/or slowly gellage in aqueous fluids. The support-platform may comprise polymers such as hydroxypropylimethylcellulose, plasticizers such as glyceride, binders such as polyvinylpyrrolidone, hydrophillic agents such as lactose and silica, and/or hydrophobic agents such as magnesium stearate and glycerides . . . Preferably the paroxetine is suitably in the form of the [crystalline] hydrochloride hemihydrate [which may be] prepared according to the procedures generally outlined in U.S. Pat. No. 4,721,723.”
There has been a need in the art to provide novel processes for incorporating paroxetine, a poorly water soluble drug, into a solid dispersion and its use in pharmaceutical compositions containing the same.
SUMMARY OF THE INVENTION
These objects, and others which will become apparent from the following disclosure, are achieved by the present invention which, in one aspect, comprises a process for preparing solid, amorphous paroxetine comprising:
(A) mixing paroxetine free base or a pharmaceutically acceptable paroxetine salt with water and pharmaceutically acceptable polymer; and
(B) drying to form a composition comprising amorphous paroxetine and polymer.
In another aspect, the invention comprises a pharmaceutical composition comprising paroxetine salt in amorphous, solid form, and polymer, prepared by the aforementioned process.
A still further aspect of the invention is a process of treating a warm-blooded animal comprising administering the pharmaceutical composition prepared according to this invention.
The aqueous solvent process of the invention eliminates the need for organic solvents and provides an amorphous solid form having distinct advantages over the crystalline form of the prior art.
REFERENCES:
patent: 5597826 (1997-01-01), Howard et al.
patent: 0 810 224 A1 (1997-12-01), None
patent: 95/16448 (1995-06-01), None
patent: 98/31365 (1998-07-01), None
patent: 99/00131 (1999-01-01), None
Chang Sou-Chan
Hein, II William A.
Kao Huai-Hung D.
Endo Pharmaceuticals Inc.
Schrader Harrison Segal & Lewis LLP
Spear James M.
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