Dry powder inhaler devices, multi-dose dry powder drug packages, control systems, and associated methods

Abstract

Dry powder inhalers with integrated active energy patient assist dispersal systems are configured with control systems which provide adjustable energy output responsive to the user's inspiratory capabilities and / or the flowability of the dry powder drug being administered. The multi-dose dry drug package includes a piezoelectric polymer substrate (such as PVDF) which flexes to deform and provide mechanical oscillation in a selected region of the package corresponding to the dry powder drug dose in the exit flow path and is thus actively dispersed into the exit flow path of the inhaler during the user's inspiratory activity. Control systems employ fuzzy logic models of the flowability of particular drug formulations (also being able to compensate or allow for the particular type of excipient used) and / or adjust for the real-time measured inspiratory efforts of the user. Manufacturing process control systems can adjust certain parameters in response to a fuzzy logic model of the flowability of the dry powder and other conditions associated with the dry powder drug being produced and / or dispensed.

Description

RELATED APPLICATIONS [0001] This application is a divisional patent application which claims the benefit of the filing date of U.S. patent application Ser. No. 10 / 204,609, filed Aug. 22, 2002, which claims benefit to PCT International Patent Application Serial No. PCT / US01 / 02262, filed Jan. 24, 2001, which claims priority to U.S. Provisional Patent Application Ser. No. 60 / 188,543, filed Mar. 10, 2000, the disclosures of which are incorporated herein by reference in their entirety.TECHNICAL FIELD [0002] The present invention relates generally to drug delivery devices and more particularly to dose-regulated dry powder inhalers. BACKGROUND ART [0003] Delivery of drugs as inhaled aerosols is well known. Indeed, asthma and other respiratory ailments have long been treated with inhaled aerosols. Presently, there is also an interest in expanding this administration concept to locally acting agents such as antimicrobials, protease inhibitors, and nucleic acids / oligios as well as systemic ag...

AI Technical Summary

Benefits of technology

[0012] It is therefore an object of the present invention to provide an improved dry powder inhaler which can disperse more uniform doses.

[0013] It is another object of the present invention to provide a DPI system to actively facilitate the dispersion and release of dry powder drug formulations during inhalation which can increase the quantity of fine particle fraction particles dispersed or emitted from the device over convention DPI systems.

[0014] It is another object of the present invention to provide an economic, disposable blister package configuration with active dispersion elements and multiple dry powder doses positioned thereon to reduce the cleaning difficulty and frequency of the inhaler.

Problems solved by technology

Alternatives to the pMDI devices are an important area of aerosol delivery research primarily because the number of non-CFC propellants is limited and reformulation is difficult.

Until recently, use of these nebulizer-type devices was typically limited to clinical sites and the home due primarily to their power requirements.

However, because the droplets are very small (such as on the order of less than about 2.0 μm), a relatively long treatment time is usually required to deliver a clinically significant dose.

Unfortunately, this passive operation can lead to poor dosing uniformity since inspiratory capabilities can vary from patient to patient (and sometimes even use to use by the same patient, particularly if the patient is undergoing an asthmatic attack or respiratory-type ailment which tends to close the airway).

If the patient is unable to provide sufficient respiratory effort, the extent of drug penetration, especially to the lower portion of the airway, may be impeded.

This may result in premature deposit of the powder in the patient's mouth or throat.

Further, a number of obstacles can desirably affect the performance of the DPI.

For example, the small size of the inhalable particles in the dry powder drug mixture can subject them to forces of agglomeration and / or cohesion (i.e., certain types of dry powders are susceptible to agglomeration, which is typically caused by particles of the drug adhering together), which disadvantageously results in poor flow and non-uniform dispersion.

However, separation of the drug from the excipient as well as the presence of agglomeration can require additional inspiratory effort, which again, can impact the stable dispersion of the powder within the airstream of the patient such that it reaches its preferred deposit / destination site and reduces the amount of the drug which is prematurely deposited elsewhere.

Further, many dry powder inhalers can retain a significant amount of the drug within the device, which can be especially problematic over time.

Typically, this problem requires that the device be cleansed to assure that it is in proper working order.

In addition, the hygroscopic nature of many of these dry powder drugs may also require that the device be cleansed (and dried) at periodic intervals.

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