Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid

Patent metadata

Field	Value
Publication number	US-9827324-B2
Application number	US-201213586380-A
Country	US
Kind code	B2
Filing date	Aug 15, 2012
Priority date	Dec 31, 2003
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

An inhalable formulation containing SAE-CD and corticosteroid is provided. The formulation is adapted for administration to a subject by nebulization with any known nebulizer. The formulation can be included in a kit. The formulation is administered as an aqueous solution, however, it can be stored as a dry powder, ready-to-use solution, or concentrated composition. The formulation is employed in an improved nebulization system for administering corticosteroid by inhalation. SAE-CD present in the formulation significantly enhances the chemical stability of budesonide. A method of administering the formulation by inhalation is provided. The formulation can also be administered by conventional nasal delivery apparatus.

First claim

The invention claimed is:

1. A method of treating a disease or disorder of the airways in a subject in need thereof, comprising administering via pulmonary inhalation to the subject an aqueous liquid formulation comprising an aqueous liquid carrier, a sulfoalkyl ether cyclodextrin (SAE-CD), and a dose of corticosteroid dissolved therein, wherein
i. the SAE-CD has the structure:

wherein:
each R is independently —H or —(CH 2 ) 4 SO 3 Na;
wherein the average degree of substitution of —(CH 2 ) 4 SO 3 Na is 6.0 to 7.1 per cyclodextrin molecule;
ii. the corticosteroid is budesonide; and
iii. the formulation provides an enhanced pharmacokinetic profile over a suspension based formulation administered under similar conditions, wherein the molar ratio of SAE-CD to corticosteroid is greater than 10:1, and wherein more than 50 % by weight of the corticosteroid is complexed with the SAE-CD.

2. The method of claim 1 , wherein the formulation is administered with a nebulizer selected from the group consisting of an air jet nebulizer, ultrasonic nebulizer, electronic nebulizer, vibrating membrane nebulizer, vibrating mesh nebulizer, and a vibrating plate nebulizer.

3. A method of treating a disease or disorder of the airways in a subject in need thereof, comprising administering via pulmonary inhalation to the subject an aqueous liquid formulation comprising an aqueous liquid carrier, a sulfoalkyl ether cyclodextrin (SAE-CD), and a dose of corticosteroid dissolved therein, wherein
i. the SAE-CD has the structure:

wherein:
each R is independently —H or —(CH 2 ) 4 SO 3 Na;
wherein the average degree of substitution of —(CH 2 ) 4 SO 3 Na is 6.0 to 7.1 per cyclodextrin molecule;
ii. the corticosteroid is budesonide; and
iii. the formulation provides an enhanced pharmacokinetic profile over a suspension based formulation administered under similar conditions, wherein the molar ratio of SAE-CD to corticosteroid is greater than 10:1, wherein more than 50% by weight of the corticosteroid is complexed with the SAE-CD, and wherein the formulation comprises nebulized droplets having a particle size of 0.5to 5 microns.

Assignees

• Pipkin James D
• Zimmerer Rupert O
• Thompson Diane O
• Mosher Gerold L
• Cydex Pharmaceuticals Inc

Inventors

• Pipkin James D
• Zimmerer Rupert O
• Thompson Diane O
• Mosher Gerold L

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P27/14

  Decongestants or antiallergics · CPC title

• A61P27/16

  Otologicals · CPC title