Drug – bio-affecting and body treating compositions – Effervescent or pressurized fluid containing – Organic pressurized fluid
Reexamination Certificate
2000-07-17
2002-10-01
Bawa, Raj (Department: 1616)
Drug, bio-affecting and body treating compositions
Effervescent or pressurized fluid containing
Organic pressurized fluid
C424S045000, C424S489000
Reexamination Certificate
active
06458338
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a medicinal aerosol formulation, and more particularly, to a medicinal aerosol formulation comprising a stabilizer selected from an amino acid, a derivative thereof or a mixture of the foregoing.
DESCRIPTION OF THE RELATED ART
Delivery of drugs to the lung by way of inhalation is an important means of treating a variety of conditions, including such common local conditions as bronchial asthma and chronic obstructive pulmonary disease and some systemic conditions including pain management, cystic fibrosis, etc. Steroids, &bgr;2 agonists, anticholinergic agents, non-steroidal antuinflammatory agents, proteins and polypeptides are among the drugs that are administered to the lung for such purposes. Such drugs are commonly administered to the lung in the form of an aerosol of particles of respirable size (less than about 10 &mgr;m in diameter). In order to assure proper particle size in the aerosol, particles can be prepared in respirable size and then incorporated into a suspension formulation containing a propellant. Alternatively, formulations can be prepared in solution form in order to avoid the concern for proper particle size in the formulation. Solution formulations must nevertheless be dispensed in a manner that produces particles or droplets of respirable size.
Once prepared an aerosol formulation is filled into an aerosol canister equipped with a metered dose valve. In the hands of the patient the formulation is dispensed via an actuator adapted to direct the dose from the valve to the patient.
It is important that an aerosol formulation be stable such that the pressurized dose discharged from the metered dose valve is reproducible. Rapid creaming, settling, or flocculation after agitation are common sources of dose irreproducibility in suspension formulations. This is especially true where a binary aerosol formulation containing only medicament and propellant, e.g. 1,1,1,2-tetrafluoroethane, is employed or where such formulation contains small amounts of surfactant as well. Sticking of the valve also can cause dose irreproducibility. In order to overcome these problems aerosol formulations often contain surfactants, which serve as suspending aids to stabilize the suspension for a time sufficient to allow for reproducible dosing. Certain surfactants also function as lubricants to lubricate the valve to assure smooth actuation. Myriad materials are known and disclosed for use as dispersing aids in aerosol formulations. Suitability of materials, however, is dependent on the particular drug and the propellant or class of propellant used in the formulation.
It is sometimes difficult to dissolve sufficient quantities of conventional surfactants in hydrofluorocarbon (HFC) propellants such as HFC-134a and HFC-227. Cosolvents, such as ethanol, have been used to overcome this problem, as described in U.S. Pat. No. 5,225,183. An alternative approach that avoids cosolvents involves materials that are soluble in hydrofluorocarbon propellants and are said to be effective surfactants or dispersing aids in an aerosol formulation. Among such materials are certain fluorinated surfactants and certain polyethyoxysurfactants.
SUMMARY OF THE INVENTION
It has surprisingly been found that novel medicinal aerosol formulations can be obtained without the use of either cosolvents, such as ethanol, or surfactants, such as sorbitan trioleate which are added to a binary aerosol formulation. Stable medicinal aerosol formulations are obtained by the use of amino acids, derivatives thereof or a mixture of the foregoing.
REFERENCES:
patent: 2868691 (1959-01-01), Porush et al.
patent: 2885427 (1959-05-01), Ruh et al.
patent: 3261748 (1966-07-01), Larsen
patent: 4129603 (1978-12-01), Bell
patent: 4174295 (1979-11-01), Bargigia et al.
patent: 5126123 (1992-06-01), Johnson
patent: 5182097 (1993-01-01), Byron et al.
patent: 5190029 (1993-03-01), Byron et al.
patent: 5225183 (1993-07-01), Purewal et al.
patent: 5254330 (1993-10-01), Ganderton et al.
patent: 5376386 (1994-12-01), Ganderton et al.
patent: 5439670 (1995-08-01), Purewal et al.
patent: 5474759 (1995-12-01), Fassberg et al.
patent: 5492688 (1996-02-01), Byron et al.
patent: 5569450 (1996-10-01), Duan et al.
patent: 5594015 (1997-01-01), Kurtz et al.
patent: 5603918 (1997-02-01), McNamara
patent: 5605674 (1997-02-01), Purewal et al.
patent: 5607662 (1997-03-01), Baskeyfield et al.
patent: 5612053 (1997-03-01), Baichwal et al.
patent: 5635159 (1997-06-01), Fu et al.
patent: 5653962 (1997-08-01), Akehurst et al.
patent: 5658549 (1997-08-01), Akehurst et al.
patent: 5674471 (1997-10-01), Akehurst et al.
patent: 5674472 (1997-10-01), Akehurst et al.
patent: 5676929 (1997-10-01), Akehurst et al.
patent: 5676931 (1997-10-01), Adjei et al.
patent: 5683676 (1997-11-01), Akehurst et al.
patent: 5683677 (1997-11-01), Purewal et al.
patent: 5688782 (1997-11-01), Neale et al.
patent: 5695743 (1997-12-01), Purewal et al.
patent: 5720940 (1998-02-01), Purewal et al.
patent: 5725841 (1998-03-01), Duan et al.
patent: 5736124 (1998-04-01), Akehurst et al.
patent: 5744123 (1998-04-01), Akehurst et al.
patent: 5891419 (1999-04-01), Cutie et al.
patent: 5891420 (1999-04-01), Cutie
patent: 6129905 (2000-10-01), Cutie et al.
patent: 6136294 (2000-10-01), Adjei et al.
patent: 6193954 (2001-02-01), Adjei et al.
patent: 2075058 (1991-01-01), None
patent: 0518660 (1992-12-01), None
patent: 2046093 (1980-11-01), None
patent: 90/09781 (1990-02-01), None
patent: 92/22287 (1992-06-01), None
patent: 93/11745 (1992-12-01), None
patent: 95/17195 (1994-11-01), None
patent: 96/18384 (1996-06-01), None
M. Jones, New Scientist, pp. 56-59, May 26, 1988.
Manufacturing Chemist, p. 3, Jun. 1988.
Organic Chemicals Department, E.I. Du Pont de Nemocers & Co., Research Disclosure, p. 70, Oct. 1977.
H.O. Spauschus, Rev. Int. Froid., vol. 11, pp. 389-392 (1988).
D.R. Strobach, Aerosol Age, pp. 32-43 (1988).
Saunders, “handbook of Aerosol Technology” 2nded. pp. 30-35, 166-167, and 232-233, Von Nostrand Reinhold Co. (1979).
DuPont Update “Fluorocarbon/Ozone”, published by DuPont, Willington, DE (Mar. 1987).
Dictionnarie Vidal, 55thed. pp. 547-548, O.V.P. Paris (1979).
Adjei Akwete
Cutie Anthony J.
Aeropharm Technology Incorporated
Bawa Raj
Frommer & Lawrence & Haug LLP
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