Respirable agglomerates of porous carrier particles and micronized drug

• US 9,744,178 B2
• Filed: 08/17/2016
• Issued: 08/29/2017
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Hartman, Michael, Tarara, Thomas E, Teung, Patrick, Weers, Jeffry G
• Primary Examiner(s): Shomer, Isaac
• Application Number:
  US15/238,842
• Publication Number:
  US 20160354388A1
• Time in Patent Office: 377 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4704 2-Quinolinones, e.g. carbostyril
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• 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 9/1682 Processes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system

Abstract

Embodiments of the present invention provide a dry powder composition comprising porous carrier particles associated with one, two, three or more micronized drugs or APIs wherein an ordered mixture between the micronized drug or drugs and the carrier particle results, such that the micronized drug or drugs adhere strongly to the carrier particles forming a stable ordered mixture of respirable agglomerates. Embodiments of the present invention further comprise a spray-drying process to create the respirable agglomerates. Embodiments of the present invention further relate to the use of the dry powder formulation comprising respirable agglomerates for the treatment of a patient having a disease or condition which is treatable thereby.

Claims

1. A process for making a dry powder formulation of respirable agglomerate particles, the process comprising the steps of:

(a) preparing a first feedstock comprising a hydrophobic excipient dispersed in an aqueous liquid phase and spray-drying said first feedstock to provide a bulk powder composition comprising a plurality of small porous powder carrier particles;

(b) providing at least a first active drug ingredient to having a size of at least 50% having a geometric diameter of less than 3 microns;

(c) preparing a second feedstock comprising a suspension of the carrier particles of step (a) and the drug particles of step (b) in a non-aqueous anti-solvent; and

(d) subjecting the second feedstock to a solvent removal process to yield a bulk powder formulation comprising an ordered mixture of respirable aggregate particles comprising small porous carrier particles and micronized drug particles, wherein the respirable agglomerate particles are characterized by a tapped density of 0.03 to 0.5 g/cm³, and a FPF<sub><

4.7 μ

m</sub> of at least about 50%.

2. The process of claim 1 wherein the hydrophobic excipient comprises DSPC and calcium chloride.

3. The process of claim 2 wherein the first active comprises a beta adrenoreceptor agonist, and the second active comprises an anti-inflammatory.

4. The process of claim 3 wherein the beta adrenoreceptor agonist comprises indacaterol, and the anti-inflammatory comprises mometasone.

5. The process of claim 4 and further including a third active.

6. The process of claim 5 wherein the third active comprises a glycopyrrolate.