Delivery of Submicrometer and Nanometer Aerosols to the Lungs using Hygroscopic Excipients or Dual Stream Nasal Delivery

Abstract

Pharmaceutically engineered aerosols (e.g. submicrometer and nano-particles and droplets) containing a hygroscopic growth excipient or agent are employed to improve the delivery of respiratory aerosols to the lung. Inclusion of the hygroscopic agent results in near zero depositional loss in the nose-mouth-throat regions and near 100% deposition of the aerosol in the lung. Targeting of the aerosol to specific lung depths is also possible. In addition, methods and apparatuses for delivering aerosols to the lung are provided. The aerosol is delivered to one nostril of a patient while a relatively high humidity gaseous carrier is delivered to the other nostril, resulting in post-nasopharyngeal growth of the aerosol to a size that promotes deposition in the lung.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]The invention generally relates to improved lung deposition of aerosols. In particular, in one embodiment, the invention provides aerosol formulations which are pharmaceutically engineered and formulated to contain hygroscopic excipients, and in another embodiment or a variation of the first embodiments, provides methods, apparatuses and systems for improved delivery of aerosols to the lungs using dual stream nasal delivery.[0003]2. Background of the Invention[0004]Nanoparticle aerosol drug delivery presents an advantageous route of administration for both locally and systemically acting pharmaceuticals. Inhaled nanoparticles in the size range of 40-1000 nm are capable of efficiently penetrating the mouth-throat (MT), nasal, and tracheobronchial (TB) regions of the lungs. Indeed, this nanoparticle size is optimum for transport into the peripheral lung regions, including the alveoli. However, once in the deep lung region...

AI Technical Summary

Benefits of technology

[0009]In one embodiment, denominated enhanced excipient growth (EEG), the present invention provides aerosolized submicrometer- or “nanometer”-sized drug particles and / or droplets which contain at least one hygroscopic excipient. The presence of the hygroscopic excipient facilitates particle / droplet growth during lung airway transit to a size that is generally not exhaled but rather is deposited in the lung. The hygroscopic excipient generally has a hygroscopic parameter of at least about 5 to about 80 or greater (in some embodiments, up to about 500, e.g. about 90, 100, 150, 200, 250, 300, 350, 400, or 450 or more), and usually at least 7 or greater. While prior art nanoparticles may exhibit some size increase upon exposure to the in viva relative humidity of the lungs (˜99.5%), the increase is insufficient to significantly increase lung retention. Therefore, a significant fraction of prior art drug particles are exhaled, and the medication is wasted. Incorporation of a hygroscopic excipient or agent in the appropriate proportions into the pharmaceutically engineered drug particles / droplets of the invention causes sufficient particle size growth to cause the particles / droplets to deposit in the lung. As a result, the initially small aerosol size results in significantly decreased extrathoracic (mouth-throat or nasal) deposition, and the subsequent aerosol size increase then results in improved lung delivery and allows for targeting the site of deposition. Therefore, less medication is wasted, more medication is delivered to an individual to whom the aerosol is administered, and the amount of medication that is delivered with each administration is more consistent, both for a single individual, and when comparing different individuals. In addition, the rate and extent of aerosol size growth can be controlled by the selection of the appropriate hygroscopic excipient(s) together with selection of the ratio of drug(s) and hygroscopic excipient(s) present in the particles or droplets.

Problems solved by technology

While prior art nanoparticles may exhibit some size increase upon exposure to the in viva relative humidity of the lungs (˜99.5%), the increase is insufficient to significantly increase lung retention.

Therefore, a significant fraction of prior art drug particles are exhaled, and the medication is wasted.

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