Pharmaceutical composition for inhalation

• US 9,517,204 B2
• Filed: 09/13/2012
• Issued: 12/13/2016
• Est. Priority Date: 09/14/2011
• Status: Active Grant

• Current Assignee: Shionogi & Co., Ltd., Shizuoka Prefectural Universities Corporation
• Original Assignee: Shionogi & Co., Ltd., Shizuoka Prefectural Universities Corporation
• Inventors: Onoue, Satomi, Yamada, Shizuo
• Primary Examiner(s): Soroush, Ali
• Assistant Examiner(s): Alley, Genevieve S
• Application Number:
  US14/344,467
• Publication Number:
  US 20140341998A1
• Time in Patent Office: 1,552 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to a powder formulation which reduces side effect risk of a medicine having a side effect of drug-induced photodermatosis and increases therapeutic effect, and relates to the method for producing the same.

Said powder formulation makes inhalation therapy possible by carrying out aerosolization easily, and since pharmacological effect in lung local part is increased, it is possible to decrease the dose. Skin transmigration of said medicine is controlled by a lung specific delivery technology, and photodermatosis which is a side effect can be controlled.

Claims

1. A powder formulation comprising:

(i) micronized particles with a mean particle diameter of 20 μ

m or less comprising

(i-1) pirfenidone and

(i-2) at least one excipient selected from the group consisting of a saccharide, a sugar alcohol, a fatty acid and salts thereof, a wax, calcium sulfate, calcium carbonate, talc and titanium oxide,

wherein the micronized particles exclude a polymer, and

(ii) a carrier with a mean particle diameter of 10 to 200 μ

m, wherein the micronized particles are adhered to the carrier.

2. The powder formulation according to claim 1, wherein a particle diameter of the micronized particles is smaller than a mean particle diameter of the carrier.

3. The powder formulation according to claim 1, wherein the saccharide is lactose.

4. The powder formulation according to claim 1, wherein the sugar alcohol is erythritol.

5. The powder formulation according to claim 1, wherein the excipient is erythritol and the carrier is lactose.

6. The powder formulation according to claim 1, wherein a weight ratio between the pirfenidone and the excipient is in the range of 1:

5000 to 10;

1.

7. The powder formulation according to claim 1, wherein a weight ratio between the micronized particles and the carrier is in the range of 1:

100 to 10;

1.

8. The powder formulation according to claim 1, wherein a mean diameter of the micronized particles is in the range of 1 to 9 μ

m.

9. The powder formulation according to claim 1, wherein the powder formulation is a transpulmonary inhalation formulation.

10. The powder formulation according to claim 1, wherein a drug-inducement of photodermatosis of the pirfenidone has been reduced as compared with an oral administration formulation.

11. A process for producing the formulation according to claim 1, comprising:

mixing micronized particles with a mean particle diameter of 20 μ

m or less comprising pirfenidone and an excipient with a carrier having a particle diameter of 10 to 200 μ

m.

12. The process according to claim 11, wherein the micronized particles are prepared by mixing the pirfenidone and the excipient to obtain a mixture, and then micronizing the mixture with a jet mill.

13. The process according to claim 12, wherein the micronized particles and the carrier are mixed in a container made from nylon or polyethylene.

14. The process according to claim 11, wherein the micronized particles and the carrier form a complex.

15. An inhalation formulation obtained by the process according to claim 11.