Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
2000-08-15
2003-06-24
Dodson, Shelley A. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S043000, C424S490000, C424S491000, C424S499000, C514S002600, C514S951000, C514S952000
Reexamination Certificate
active
06582729
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to powdered pharmaceutical compositions that exhibit improved dispersibility for inhalation therapy, to processes for preparing such compositions and to methods for treating certain disease states using such compositions.
BACKGROUND OF THE INVENTION
Over the years, certain drugs have been sold in compositions suitable for forming a drug dispersion for oral inhalation (pulmonary delivery) to treat various conditions in humans. Such pulmonary drug delivery compositions are designed to be delivered by inhalation of a drug dispersion by the patient so that the active drug within the dispersion can reach the lung. It has been found that certain drugs delivered to the lung are readily absorbed through the alveolar region directly into blood circulation. Pulmonary delivery is particularly promising for the delivery of proteins and polypeptides which are difficult to deliver by other routes of administration. Such pulmonary delivery can be effective both for systemic delivery and for localized delivery to treat diseases of the lungs.
Pulmonary drug delivery can itself be achieved by different approaches, including liquid nebulizers, aerosol-based metered dose inhalers (MDI's), and dry powder dispersion devices. Aerosol-based MDI's are losing favor because they rely on the use of chlorofluorocarbons (CFC's), which are being banned because of their adverse effect on the ozone layer. Dry powder dispersion devices, which do not rely on CFC aerosol technology, are promising for delivering drugs that may be readily formulated as dry powders, particularly proteins and polypeptides. Many otherwise labile proteins and polypeptides may be stably stored as lyophilized or spray-dried powders by themselves or in combination with suitable powder carriers. The ability to deliver proteins and polypeptides as dry powders, however, is problematic in certain respects. The dosage of many protein and polypeptide drugs is often critical so it is necessary that any dry powder delivery system be able to accurately, precisely, and reliably deliver the intended amount of drug. Moreover, many proteins and polypeptides are quite expensive, typically being many times more costly than conventional drugs on a per-dose basis. Thus, the ability to efficiently deliver the dry powders with a minimal loss of drug is critical. It is also important that the powder be readily dispersible prior to inhalation by the patient in order to assure adequate distribution and systemic absorption.
A particularly promising approach for the pulmonary delivery of dry powder drugs utilizes a hand-held device with a hand pump for providing a source of pressurized gas. The pressurized gas is abruptly released through a powder dispersion device, such as a venturi nozzle, and the dispersed powder made available for patient inhalation. While advantageous in many respects, such hand-held devices are problematic in a number of other respects. The particles being delivered are less than 10 &mgr;m in size, usually in the range from 1 &mgr;m to 5 &mgr;m, making powder handling and dispersion more difficult than are larger particles. The problems are exacerbated by the relatively small volumes of pressurized gas, which are available using hand-actuated pumps. In particular, venturi dispersion devices are unsuitable for difficult-to-disperse powders when only small volumes of pressurized gas are available. Another requirement for hand-held and other powder delivery devices is efficiency. It is important that the concentration of drug in the bolus of gas be relatively high to reduce the number of breaths required to achieve a total dosage. The ability to achieve both adequate dispersion and small dispersed volumes is a significant technical challenge that requires in part that each unit dosage of the powdered composition be readily and reliably dispersible.
OBJECTS OF THE INVENTION
An object of this invention is to provide a powdered pharmaceutical composition containing a drug suitable for pulmonary delivery that exhibits improved dispersibility over compositions known in the art and thus more reliable pulmonary delivery of the drug.
A further object of this invention is to provide a powdered pharmaceutical composition containing a drug suitable for pulmonary delivery that provides the amount of drug from a unit dosage form accurately, precisely and reliably.
A further object of this invention is to provide a powdered pharmaceutical composition containing a drug suitable for pulmonary delivery that exhibits the efficient delivery of drug with minimal loss per unit dosage form.
A further object of this invention is to provide a highly dispersible powdered pharmaceutical formulation containing nucleic acid plasmids (particularly a cationic lipid:DNA complex or recombinant viral particles having the desired DNA) suitable for pulmonary delivery.
A further object of this invention is to provide a process for preparing a powdered pharmaceutical composition containing a drug suitable for pulmonary delivery, which composition shows improved dispersibility over compositions known in the art.
A further object of this invention is to provide a method for treating a subject having a condition susceptible to treatment by inhalation, particularly oral inhalation, which method comprises administering the composition of this invention that exhibits improved dispersibility.
Other objects of this invention will be apparent to one of ordinary skill in the art upon reading the full specification and claims of this patent application.
SUMMARY OF THE INVENTION
One aspect of this invention is a dispersible dry power composition that is suitable for administration to a subject by inhalation, and that comprises a pharmaceutically-acceptable excipient, a therapeutically effective amount of an active agent suitable for treating a condition susceptible to treatment by oral inhalation, and a dispersibility-enhancing amount of a pharmaceutically acceptable polypeptide, e.g., HSA. Alternatively, an aspect of this invention can be viewed as an improvement over existing powdered pharmaceutical compositions suitable for inhalation therapy, in that the improvement comprises the presence of a dispersibility-enhancing amount of a pharmaceutically acceptable polypeptide in the powdered pharmaceutical composition.
Another aspect of this invention is a method of administering a therapeutically effective amount of a powdered composition of this invention to a human subject in need thereof by dispersing said powdered composition as an aerosol into a chamber having a delivery outlet suitable for inhalation therapy, e.g., a mouthpiece and having said subject inhale, preferably orally, said dispersed powder into the subject's lungs.
Another aspect of this invention is an improvement in a process for preparing a respirable powdered pharmaceutical composition. In a process for preparing a respirable powdered pharmaceutical composition by (a) forming a homogeneous aqueous composition comprising water, a pharmaceutically acceptable excipient and an active agent suitable for treating a disease state by inhalation, (b) removing the water from the aqueous composition to form a solid and (c) transforming the resulting solid into a respirable powdered pharmaceutical composition, the improvement of this invention comprises adding a water-soluble, physiologically-acceptable protein (e.g., HSA) to the aqueous composition in an amount sufficient to enhance the dispersibility of the resulting respirable powdered pharmaceutical composition.
Another, more specific, aspect of this invention is a method for preparing a spray-dried, dispersible powdered pharmaceutical composition that comprises spray drying a homogeneous aqueous mixture comprising water, a pharmaceutically acceptable excipient, an active agent suitable for treating a disease state by inhalation, and a dispersibility-enhancing amount of a physiologically acceptable, water-soluble protein under conditions sufficient to provide a dispersible powdered pharmaceutical composition havin
Eljamal Mohammad
Foster Linda C.
Patton John S.
Platz Robert M.
Cagan Felissa H.
Dodson Shelley A.
Evans Susan T.
Naktar Therapeutics
Wilson Mark A.
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