Dosator apparatus for filling a capsule with dry powder

• US 9,642,812 B2
• Filed: 05/08/2015
• Issued: 05/09/2017
• Est. Priority Date: 11/09/2012
• Status: Active Grant

• Current Assignee: Civitas Therapeutics, Inc. (Acorda Therapeutics Incorporated)
• Original Assignee: Civitas Therapeutics, Inc. (Acorda Therapeutics Incorporated)
• Inventors: Penachio, Ernest D., LaVigne, Kyle
• Primary Examiner(s): Arnett, Nicholas A
• Application Number:
  US14/707,053
• Publication Number:
  US 20150342890A1
• Time in Patent Office: 732 Days
• Field of Search: 141 11- 12, 141 71, 141 81, 141392
• CPC Class Codes: A61J 3/074 Filling capsules; Related operations
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• 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 9/145 with organic compounds
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: B65B 1/16 by pneumatic means, e.g. by suction
• CPC Class Codes: B65B 1/26 by pneumatic means, e.g. suction
• CPC Class Codes: B65B 1/36 by volumetric devices or methods checking volume of filled material B65B1/48
• CPC Class Codes: B65B 63/028 by pneumatic means

Abstract

The invention relates to a dosator which comprises a tapered elongate cavity; a stationary plunger disposed within the cavity; a removable mesh screen disposed between the stationary plunger and the bottom of the dosator; a dosator chamber defined between the mesh screen and the bottom of the dosator for receiving powder from a powder source and holding the powder until it is expelled into the capsule; at least one vacuum pump operably linked to the dosator and capable of drawing dry powder into the dosator chamber from a powder source, compacting the powder into a slug of powder having a predetermined bulk density; and at least one source of positive pressure operably linked to the dosator and capable of providing positive pressure to expel the powder slug from the dosator and methods of filling capsules.

Claims

1. A method of filling a capsule, the method comprising the steps of:

creating a low pressure vacuum within a dosator;

positioning the dosator in a bowl filled with dry powder and drawing the dry powder into the dosator chamber;

maintaining the dry powder in the dosator chamber with the low pressure vacuum to form a slug of powder having a predetermined bulk density; and

expelling the slug of powder into a capsule;

wherein the dry powder is characterized by a fine particle fraction of 40% or more and a mass mean geometric diameter of between about 5 μ

m and about 18 μ

m;

wherein the dosator comprises;

an elongate cavity which tapers from the top of the dosator to the bottom of the dosator;

a stationary plunger disposed within the cavity;

a removable mesh screen having a mesh size that is smaller than the mass median diameter (D₅₀) of the dry powder and between about 2 and 5 um disposed between the stationary plunger and the bottom of the dosator;

a dosator chamber defined between the mesh screen and the bottom of the dosator for receiving powder from a powder source and holding the powder until it is expelled into the capsule;

at least one vacuum pump operably linked to the dosator and capable of drawing dry powder into the dosator chamber from a powder source, compacting the powder into a slug of powder having a predetermined bulk density and expelling the slug of powder into a capsule;

at least one source of positive pressure operably linked to the dosator and capable of providing positive pressure to expel the powder slug from the dosator.

2. The method of claim 1, wherein said bulk density of the powder slug is between about 0.02 g/cm³ to about 0.05 g/cm³.

3. The method of claim 1, wherein the capsule is a 00 size capsule.

4. The method of claim 1, wherein powder slug comprises between about 15 and 50 milligrams of powder.

5. The method of claim 1, wherein the powder slug comprises between about 25 and 35 milligrams of powder.

6. The method of claim 1, wherein the at least one vacuum pump achieves a pressure of about −

1 atmosphere (atm).

7. The method of claim 1, wherein at least two vacuum pumps achieve a pressure of about −

1 atm.

8. The method of claim 1, wherein the diameter of the dosator chamber as measured at the mesh screen is between 0.280 and 0.315 inches.

9. The method of claim 1, wherein the diameter of the dosator chamber as measured at the mesh screen is 0.286 inches.

10. The method of claim 1, wherein the bowl is filled with powder to achieve a bed height that is twice the stroke height of the dosator.

11. The method of claim 1, wherein the dosator fills a 00 capsule with about 25-50 mg of powder.

12. The method of claim 1, wherein the dosator fills the 00 capsule with at least 30 mg of dry powder.

13. The method of claim 1, wherein the dosator fills 2 or more 00 capsules with about 30 mg or more of dry powder wherein the relative standard deviation in the amount of powder filled in all capsules is less than 4%.

14. The method of claim 1, wherein the dosator chamber height is in the range of 5 mm to 20 mm.

15. The method of claim 1, wherein the mesh screen is a 2 micron mesh screen.

16. The method of claim 1, wherein the mesh screen is a 5 micron mesh screen.

17. The method of claim 1, wherein the source of positive pressure is a nitrogen gas source.

18. The method of claim 1, wherein the dry powder comprises a 90:

8;

2 levodopa;

dipalmitoylphosphatidylcholine;

sodium chloride composition.

19. The method of claim 18, wherein the dry powder is a spray dried powder having a water content of between about 2% and about 4% by weight.