Title:  Powdered pharmaceutical formulations having improved dispersibility

United States Patent:  6,136,346

Assignee:  Inhale Therapeutic Systems (San Carlos, CA)

Filed:  March 17, 1998

PCT NO:  PCT/US96/05265

102(e) Date:  March 17, 1998

PCT PUB. Date:  October 17, 1996

Dispersibility of a respirable powder, administrable by inhalation, is increased by including a pharmaceutically acceptable water-soluble polypeptide.

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) foroeing 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 having a particle size less than about ten microns. Alternatively, this aspect may be viewed as an improvement in a method preparing a spray-dried, dispersible, powdered pharmaceutical composition by spray drying a homogeneous aqueous mixture comprising water, a pharmaceutically acceptable excipient and an active agent suitable for treating a disease state by inhalation under conditions sufficient to provide a dispersible powder, wherein the improvement comprises including a dispersibility-enhancing amount of a physiologically acceptable, water-soluble protein in the aqueous mixture.

Claim 1 of 16 Claims

What is claimed is:

1. A method of preparing a spray-dried, dispersible powdered pharmaceutical composition, comprising:

spray-drying a homogeneous aqueous mixture comprising a pharmaceutically-acceptable excipient, a dispersibility-enhancing, physiologically-acceptable, water-soluble polypeptide and an active agent to obtain an aerosolizable, dispersible powder composition suitable for administration to a human subject by inhalation therapy, whereby the presence of the polypeptide in the mixture is effective to increase the dispersibility of the spray-dried powder composition over the dispersibility of the

spray-drying a homogeneous aqueous mixture comprising a pharmaceutically-acceptable excipient, a dispersibility-enhancing, physiologically-acceptable, water-soluble polypeptide and an active agent to obtain an aerosolizable, dispersible powder composition suitable for administration to a human subject by inhalation therapy, whereby the presence of the polypeptide in the mixture is effective to increase the dispersibility of the spray-dried powder composition over the dispersibility of the composition prepared in the absence of said polypeptide.

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