Use of simple amino acids to form porous particles

Abstract

Particles having a tap density of less than 0.4 g / cm3 include a hydrophobic amino acid or salt thereof and a therapeutic, prophylactic or diagnostic agent or any combination thereof. Preferred particles include a phospholipid, have a median geometric diameter between about 5 and about 30 microns and an aerodynamic diameter between about 1 and about 5 microns. The particles can be formed by spray-drying and are useful for delivery to the pulmonary system.

Description

RELATED APPLICATIONS[0001]This application is a divisional of U.S. application Ser. No. 11 / 637,353, filed on Dec. 12, 2006, which is a continuation of U.S. application Ser. No. 09 / 644,320, filed Aug. 23, 2000, now U.S. Pat. No. 7,252,840, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 382,959, filed Aug. 25, 1999, now U.S. Pat. No. 6,586,008. The entire teachings of the above applications are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]Aerosols for the delivery of therapeutic agents to the respiratory tract have been described, for example, Adjei, A. and Garren, J. Pharm. Res., 7: 565-569 (1990); and Zanen, P. and Lamm, J.-W. J. Int. J. Pharm., 114: 111-115 (1995). The respiratory tract encompasses the upper airways, including the oropharynx and larynx, followed by the lower airways, which include the trachea followed by bifurcations into the bronchi and bronchioli. The upper and lower airways are called the conducting airways. The termi...

AI Technical Summary

Benefits of technology

The invention is about particles made of amino acids or salts thereof that can be used for drug delivery to the pulmonary system. These particles have a low tap density and can be spray-dried using simple solvents. They can contain therapeutic, prophylactic or diagnostic agents, as well as phospholipids. The particles can be delivered to the respiratory system, including the deep lung, central airways, and upper airways. The particles have extended release properties and improved formulability, and can be administered in higher doses with higher efficiency. The method of forming the particles is simple and cost-effective. Overall, the invention provides a safe, efficient, and cost-effective way to deliver drugs to the pulmonary system.

Problems solved by technology

However, pulmonary drug delivery strategies present many difficulties for the delivery of macromolecules; these include protein denaturation during aerosolization, excessive loss of inhaled drug in the oropharyngeal cavity (often exceeding 80%), poor control over the site of deposition, lack of reproducibility of therapeutic results owing to variations in breathing patterns, the frequent too-rapid absorption of drug potentially resulting in local toxic effects, and phagocytosis by lung macrophages.

Slow release from a therapeutic aerosol can prolong the residence of an administered drug in the airways or acini, and diminish the rate of drug appearance in the bloodstream.

However, many drugs and excipients, especially proteins, peptides (Liu, R., et al, Biotechnol. Bioeng., 37: 177-184 (1991)), and biodegradable carriers such as poly(lactide-co-glycolides) (PLGA), are unstable in aqueous environments for extended periods of time.

This can make storage as a liquid formulation problematic.

However, among the disadvantages of DPF's is that powders of ultrafine particulates usually have poor flowability and aerosolization properties, leading to relatively low respirable fractions of aerosol, which are the fractions of inhaled aerosol that escape deposition in the mouth and throat.

Furthermore, the method of delivery of these powders is associated with several disadvantages.

For example, there are inefficiencies in the release of active particles from the carrier.

Moreover, the carrier takes up significantly more volume than the active particle, thus high drug doses are difficult to achieve.

In addition, the large lactose particles can impact the back of the throat, causing coughing.