Composition for pulmonary administration comprising a drug and a hydrophobic amino acid

Abstract

According to the subject invention. dispersible dry powder pharmaceutical-based compositions are provided. including methods for their manufacture and dry powder dispersion devices. A dispersible dry powder pharmaceutical-based composition is one having a moisture content of less than about 10% by weight (% w) water, usually below about 5% w and preferably less than about 3% w; a particle size of about 1.0-5.0 .mu.m mass median diameter (MMD), usually 1.0-4.0 .mu.m MMD, and preferably 1.0-3.0 .mu.m MMD; a delivered dose of about >30%, usually >40%, preferably >50%, and most preferred >60%: and an aerosol particle size distribution of about 1.0-5.0 .mu.m mass median aerodynamic diameter (MMAD), usually 1.5-4.5 .mu.m MMAD, and preferably 1.5-4.0 MMAD. Such composition are of pharmaceutical grade purity.

Description

[0001] This application is a continuation in part of the following U.S. patent application Ser. Nos.: 07 / 910,048. filed Jul. 08, 1992; 08 / ______ (attorney docket no. 15225-000410), filed Apr. 4, 1995, which is a file wrapper continuation of 08 / 044,358, filed Apr. 7, 1993; 08 / 232,849, filed Apr. 25, 1994; 08 / 309.691, filed Sep. 21 1994; 08 / 246.034, filed May 18, 1994; 08 / 313,707, filed Sep. 27, 1994; and 08 / 383.475, filed Feb. 1, 1995, the full disclosures of which are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002] 1. Field of the Invention[0003] The present invention relates generally to methods and compositions for the dry powder formulation of pharmaceuticals, including macromolecules, for pulmonary delivery.[0004] 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...

AI Technical Summary

Problems solved by technology

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.

The ability to deliver pharmaceutical compositions as dry powders, however, is problematic in certain respects.

Moreover, many pharmaceutical compositions are quite expensive.

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 .mu.m in size. usually in the range from 1 .mu.m to 5 .mu.m, making powder handling and dispersion more difficult than with 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.

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.