Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
2002-06-19
2004-03-23
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S400000, C424S464000, C424S465000
Reexamination Certificate
active
06709676
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to oral dosage compositions, including a bilayer sustained release oral dosage composition containing a nasal decongestant, e.g., pseudoephedrine in one layer and the non-sedating antihistamine, desloratadine in a second layer and having less than about 2% of desloratadine degradation products in the compositions. The oral dosage compositions of this invention are useful for treating patients showing the signs and symptoms associated with allergic and/or inflammatory conditions such as the common cold, as well as signs and symptoms associated with allergic and/or inflammatory conditions of the skin such as dermatitis, and airway passages such as the upper respiratory disease conditions, perennial allergic rhinitis, seasonal allergic rhinitis and nasal congestion, allergic asthma, and nasal congestion.
Desloratadine, also called descarbethoxyloratadine, is disclosed in U.S. Pat. No. 4,659,716 as a non-sedating antihistamine useful as an anti-allergy agent. U.S. Pat. No. 5,595,997 discloses methods and compositions for treating seasonal allergic rhinitis symptoms using desloratadine.
U.S. Pat. Nos. 4,990,535 and 5,100,675 disclose a twice-a-day sustained release coated tablet wherein the tablet coating comprises descarbethoxyloratadine and a hydrophilic polymer and polyethylene glycol, and the tablet core comprises acetaminophen, pseudoephedrine or a salt thereof, a swellable hydrophilic polymer and pharmaceutically acceptable excipients.
U.S. Pat. No. 5,314,697 discloses an extended release tablet containing matrix core comprising pseudoephedrine sulfate and a coating comprising loratadine.
None of the prior art discloses the solid oral dosage compositions of this invention.
The successful development of a formulation of a desloratadine-pseudoephedrine twice-a-day and once-a-day products would be desirable, but would require (1) achieving a release rate profile for pseudoephedrine component over an extended period of about twelve hours or twenty four hours, respectively, while maintaining the safety and effectiveness of desloratadine, and (2) minimizing impurity formation due to the interaction between desloratadine and excipients in the pseudoephedrine layer that are incompatible with desloratadine.
It would be desirable for increased patient compliance to have a stable, extended release desloratadine-pseudoephedrine product substantially free of desloratadine impurities and additional polymorphic forms that is effective and safe when used on a twice-a-day or once-a-day basis for the treatment, management and/or mitigation of the signs and symptoms associated with the common cold, as well as allergic and/or inflammatory conditions of the skin or upper and lower airway passages such as seasonal and perennial allergic rhinitis and nasal congestion.
SUMMARY OF THE INVENTION
We have found that desloratadine discolors and decomposes in the presence of excipients disclosed in the prior art. We have discovered that these problems are substantially solved by (a) bilayer solid compositions of the present invention wherein immediate release layer contains desloratadine combined with a pharmaceutically acceptable carrier medium comprising a desloratadine protective amount of a pharmaceutically acceptable basic salt, and wherein the use of an acidic excipient in the immediate release layer is substantially avoided or (b) bilayer solid compositions of the present invention wherein a desloratadine-protective amount of at least one pharmaceutically acceptable antioxidant is present in at least one layer, and preferably, wherein two of said antioxidants are present in desloratadine-containing immediate release layer.
Thus, this invention provides a bilayer solid composition comprising (a) an immediate release first layer comprising an anti-allergic effective amount of desloratadine and at least one pharmaceutically acceptable excipient and (b) a sustained release second layer comprising an effective amount of a nasal decongestant and a pharmaceutically acceptable sustained release agent wherein the total amount of desloratadine decomposition products in the composition is less than, or equal to, about 2% by weight.
REFERENCES:
patent: 3536809 (1970-10-01), Applezweig
patent: 3598123 (1971-08-01), Zaffaroni
patent: 3845770 (1974-11-01), Theeuwes et al.
patent: 3916899 (1975-11-01), Theeuwes et al.
patent: 3940485 (1976-02-01), Levinson et al.
patent: 4008796 (1977-02-01), Aylon
patent: 4282233 (1981-08-01), Vilani
patent: 4371516 (1983-02-01), Gregory et al.
patent: 4552899 (1985-11-01), Sunshine et al.
patent: 4659716 (1987-04-01), Villani et al.
patent: 4731447 (1988-03-01), Schumacher et al.
patent: 4777170 (1988-10-01), Heinrich
patent: 4783465 (1988-11-01), Sunshine et al.
patent: 4804666 (1989-02-01), Piwinski et al.
patent: 4863931 (1989-09-01), Schumacher et al.
patent: 4906647 (1990-03-01), Kouchiwa et al.
patent: 4990535 (1991-02-01), Cho et al.
patent: 5019591 (1991-05-01), Gardner et al.
patent: 5089496 (1992-02-01), Piwinski et al.
patent: 5100675 (1992-03-01), Cho et al.
patent: 5314697 (1994-05-01), Kwan et al.
patent: 5407941 (1995-04-01), Carceller et al.
patent: 5476856 (1995-12-01), Carceller et al.
patent: 5595997 (1997-01-01), Aberg et al.
patent: 5731319 (1998-03-01), Aberg et al.
patent: 5900421 (1999-05-01), Handley et al.
patent: 5939426 (1999-08-01), McCullough
patent: 6051585 (2000-04-01), Weinstein et al.
patent: 6100274 (2000-08-01), Kou
patent: 6114346 (2000-09-01), Harris et al.
patent: 6132758 (2000-10-01), Munayyer et al.
patent: 6270796 (2001-08-01), Weinstein et al.
patent: 6423721 (2002-07-01), Harris et al.
patent: 6506767 (2003-01-01), Schumacher et al.
patent: 6514520 (2003-02-01), Munayyer et al.
patent: 6521254 (2003-02-01), Weinstein et al.
patent: 0 264 259 (1988-04-01), None
patent: 0 288 640 (1988-11-01), None
patent: 0 396404 (1990-11-01), None
patent: 0 577 957 (1994-01-01), None
patent: 0 396404 (1994-02-01), None
patent: 85/03707 (1985-08-01), None
patent: 92/00293 (1992-01-01), None
patent: 92/11034 (1992-07-01), None
patent: 92/20377 (1992-11-01), None
patent: 96/16641 (1996-06-01), None
patent: 96/20708 (1996-07-01), None
patent: 98/34614 (1998-08-01), None
patent: 00/2560 (2000-01-01), None
Andersen, et al., “Adverse drug interactions clinically important for the dermatologist”, Arch Dermatol, Apr., 1995, vol. 131, pp. 468-473.
Babe, et al., “Histamine, Bradykinn, and their Antagonists” in The Pharmacological Basis of Therapeutics (9thedition), The McGraw-Hill Co. Inc., pp. 581-599 (1996).
Barnett, et al., “Pharmacology of Non-Sedating H1 Antihistamines”,New Perspectives in Histamine Research, Birkhauser Verlag Basel, pp. 181-196 (1991).
Berge,et al., “Pharmaceutical Salts”, J. of Pharm. Sciences, Jan., 1977, vol. 66, No.1 pp.1-19.
Berthon, et al., “In Vitro inhibition, by loratadine and descarboxyethoxyloratadine, of histamine release form human basophils, and of histamine release and intracellular calcium fluxes in rat basophilic leukemia cells (RBL-2H3)”, Biochem. Pharm., 1994, vol. 47, No. 5, pp. 789-794.
Blaug, et al., “Interaction of dextroamphetamine sulfate with spray-dried lactose”, J. of Pharm. Sciences, Nov., 1972, vol. 61, No. 11, pp. 1770-1775.
Brandes, et al., “Enhanced cancer growth in mice administered daily human-equivalent doses of some H1-antihistamines: predictive in vitro correlates”, J. of the National Cancer Inst., May 18, 1994, vol. 86, No. 10, pp. 770-775.
Brandes, et al., “Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses”, Cancer Research, Jul. 1, 1992, vol. 52, pp. 3796-3800.
Brion, et al., “Evaluation of the antimuscarinic activity of atropine, terfenadine and mequitazine in healthy volunteers”, Br. J. Clin. Pharmac. 1988, vol. 25, pp. 27-32.
Carmeliet, “Voltage-and Time-Dependent Block of the Delayed K+ Current in Cardiac Myocytes by Dofetilide”, The J. of Pharm. And Experimental Therapeutics, 1992, vol. 262, No. 2, pp. 809-817.
Castello, et al., “Discoloration of tablets containing amines and lactose”, J. of
Hoffman Thomas D.
Page Thurman K.
Schering Corporation
Sheikh Humera N.
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