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Heating unit for use in a drug delivery device

a heating unit and drug delivery technology, applied in the direction of aerosol delivery, heterocyclic compound active ingredients, respirators, etc., can solve the problems of poor patient compliance, inability to produce aerosol particles undetectable for systemic delivery, and limited treatment role of inhalation therapy in health care field

Inactive Publication Date: 2008-09-11
ALEXZA PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to drawbacks associated with traditional routes of administration, including slow onset, poor patient compliance, inconvenience, and / or discomfort, alternative administration routes have been sought.
However, despite such results, the role of inhalation therapy in the health care field has remained limited mainly to treatment of asthma, in part due to a set of problems unique to the development of inhalable drug formulations and their delivery modalities, especially formulations for, and delivery by, inhalation.
Metered dose inhaler formulations involve a pressurized propellant, which is frequently a danger to the environment, and generally produces aerosol particle sizes undesirably large for systemic delivery by inhalation.
Furthermore, the high speed at which the pressurized particles are released from metered dose inhalers makes the deposition of the particles undesirably dependent on the precise timing and rate of patient inhalation.
Also, the metered dose inhaler itself tends to be inefficient because a portion of the dose is lost on the wall of the actuator, and due to the high speed of ejection of the aerosol from the nozzle, much of the drug impacts ballistically on the tongue, mouth, and throat, and never gets to the lung.
While solving some of the problems with metered dose inhalers, dry powder formulations are prone to aggregation and low flowability phenomena which considerably diminish the efficiency of dry powder-based inhalation therapies.
Such problems are particularly severe for dry powders having an aerosol particle size small enough to be optimal for deep lung delivery, as difficulty of particle dispersion increases as particle size decreases.
Moreover, the dispersion of liquids generally involves complex and cumbersome devices and is effective only for solutions with specific physical properties, e.g. viscosity.
Such solutions cannot be produced for many drugs due to the solubility properties of the drug.
Volatilization, however, subjects the drug to potential chemical degradation via thermal, oxidative, and / or other means.

Method used

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  • Heating unit for use in a drug delivery device
  • Heating unit for use in a drug delivery device
  • Heating unit for use in a drug delivery device

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0143]Loperamide and flunisolide condensation aerosols were produced by the substrate screening apparatus using 304 stainless steel perforated substrates having the % porosities, hole spacings, and hole diameters shown in Table 1. The substrates were spray-coated with loperamide free base or flunisolide free base at coating densities of 0.3 mg / cm2 and 0.4 mg / cm2, respectively. Air flow ratios (across:bottom) of 23:5 and 18:10 were evaluated. The substrate was rapidly heated to approximately 400° C. for loperamide and approximately 375° C. for flunisolide.

TABLE 1Characteristics of Perforated 304 Stainless Steel SubstratesSubstrate#Hole DiameterHole Spacing% Porosity10.005″0.015″520.005″0.009″1030.005″0.005″2040.010″0.03″550.010″0.018″1060.010″0.010″2070.010″0.004″4080.020″0.059″590.020″0.036″10100.020″0.020″20110.020″0.008″40120.040″0.118″5130.040″0.016″40

[0144]Aerosol purity results for loperamide aerosolized from perforated 304 stainless steel substrates at an across:bottom air flo...

example 2

[0149]Sildenafil aerosols were produced by the substrate screening apparatus using 0.005″ thick 316 stainless steel substrates having a regular staggered pattern of circular, 0.006″ diameter holes. The holes, which were formed in the substrate by chemical etching, occupied approximately 27% of the total surface area of the substrate. The distance “d” between the holes was 3.5×10−3 in.

[0150]The substrates were spray-coated with a 15 mg / mL solution of sildenafil free base (isolated from pills, available from Pfizer, Inc., New York, N.Y.) dissolved in dichloromethane / methanol (2:1 volume:volume) at coating densities of 0.18, 0.50, and 1.07 mg / cm2 (approximate coating thicknesses: 1.8, 5.0, and 10.7 μm). Total (across+bottom) air flow rate was 28.3 liters / minute. Various airflow ratios and vaporization temperatures were evaluated.

[0151]FIG. 7 is a bar graph 700 showing aerosol purity (%) and yield (%) 702 for a sildenafil coating density of 0.18 mg / cm2 at various air flow ratio conditio...

example 3

[0154]Bumetanide condensation aerosols were produced by the substrate screening apparatus using the perforated 316 stainless steel substrates described above. The substrates were spray-coated with a 50 mg / mL solution of bumetanide free base (available from Solmag S.p.A., Garbagnate, Italy) dissolved in methanol / acetone (50:50 volume:volume) at a coating density of 0.07 mg / cm2 (approximate coating thickness: 0.7 μm). Total air flow rate was 20 liters / minute.

[0155]As discussed above, in certain cases, oxidizing the stainless steel substrates prior to drug vaporization yields increased aerosol purity. Therefore, the perforated stainless steel substrates were heat-oxidized and re-cleaned according to the procedure described above prior to coating with drug.

[0156]FIG. 9 is a bar graph 900 showing aerosol purity (%) 902 of bumetanide free base at various air flow ratios 904. As shown in graph 900, as the percentage of air flow coming across (as opposed to from under the bottom, uncoated s...

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Abstract

Drug supply units are disclosed which comprise substrates having a plurality of holes formed therein.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims the priority of earlier filed U.S. Provisional Application Ser. No. 60 / 894,116, filed Mar. 9, 2007. The entire content of that provisional application is expressly incorporated by reference herein.FIELD OF THE INVENTION[0002]The present invention relates generally to drug supply units comprising a substrate having a plurality of holes. More particularly, embodiments of the invention relate to drug supply units intended to be used to vaporize a drug composition deposited on a surface of the substrate, drug delivery devices comprising such drug supply units, and methods of producing an aerosol using such drug delivery devices.BACKGROUND OF THE INVENTION[0003]Traditionally, inhalation therapy has played a relatively minor role in the administration of therapeutic agents when compared to more traditional drug administration routes of oral delivery and delivery via injection. Due to drawbacks associated with traditiona...

Claims

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Application Information

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IPC IPC(8): A61M16/10
CPCA61K9/0009A61K9/12A61M11/041A61M15/06A61M15/0015A61M2205/8268A61M11/042A61M11/047A61M2205/3653A61M11/001A61K9/007A61K31/135A61K31/138A61K31/196A61K31/197A61K31/433A61K31/4468A61K31/451A61K31/4525A61K31/4985A61K31/519A61K31/53A61K31/5415A61K31/56A61K31/573A61K31/58A61K31/7076A61M15/00
Inventor WENSLEY, MARTIN J.GLAZER, MARCBRESSON, JAMESTIMMONS, RYANMYERS, DANIEL J.
Owner ALEXZA PHARMA INC
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