Dry powder formulations of particles that contain two or more active ingredients for treating obstructive or inflammatory airways diseases
| Title: | Dry powder formulations of particles that contain two or more active ingredients for treating obstructive or inflammatory airways diseases |
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| Patent Number: | 9,050,267 |
| Publication Date: | June 09, 2015 |
| Appl. No: | 13/982630 |
| Application Filed: | February 03, 2012 |
| Abstract: | Dry powder formulations for inhalation comprising spray-dried particles and their use in the treatment of an obstructive or inflammatory airways disease. Each particle has a core of a first active ingredient in substantially crystalline form that is coated with a layer of a second active ingredient in substantially amorphous form that is dispersed in a pharmaceutically acceptable hydrophobic excipient. A process for preparing such formulations is also described. |
| Inventors: | Weers, Jeffry G. (Belmont, CA, US); Rao, Nagaraja (San Leandro, CA, US); Huang, Daniel (Palo Alto, CA, US); Miller, Danforth (San Carlos, CA, US); Tarara, Thomas E. (Burlingame, CA, US) |
| Assignees: | Novartis AG (Basel, CH) |
| Claim: | 1. A dry powder formulation for inhalation comprising spray-dried particles that comprise a core of a first active ingredient in substantially crystalline form that is coated with a layer of a second active ingredient in substantially amorphous form that is dispersed in a pharmaceutically acceptable hydrophobic excipient. |
| Claim: | 2. A formulation according to claim 1 , wherein the active ingredients are selected from bronchodilators, anti-inflammatories, antihistamines, decongestants and anti-tussive drug substances. |
| Claim: | 3. A formulation according to claim 2 , wherein the first active ingredient is a β2-agonist and the second active ingredient is a steroid. |
| Claim: | 4. A formulation according to claim 2 , wherein the first active ingredient is a β2-agonist and the second active ingredient is an anti-muscarinic antagonist. |
| Claim: | 5. A formulation according to claim 1 , wherein the first active ingredient is a β2-agonist, the second active ingredient is an anti-muscarinic antagonist, and the formulation also contains a third active ingredient, which is a steroid. |
| Claim: | 6. A formulation according to claim 1 that further comprises a third active ingredient that is substantially amorphous and is dispersed in the hydrophobic excipient. |
| Claim: | 7. A formulation according to claim 6 wherein the active ingredients are indacaterol or a salt thereof, mometasone furoate and glycopyrrolate. |
| Claim: | 8. A formulation according to claim 1 , wherein the hydrophobic excipient is a phospholipid. |
| Claim: | 9. A formulation according to claim 1 in powdered form wherein the inhalable medicament particles comprise 0.1% to 30% w/w of a first active ingredient in substantially crystalline drug that is coated with a rugous layer comprising 0.1% to 30% of a second active ingredient in substantially amorphous form that is dispersed in a hydrophobic excipient, wherein the particles have a mass median diameter (MMD) of between 1 and 10 microns, a mass median aerodynamic diameter (MMAD) of between 1 and 5 microns, and a rugosity Sv of greater than 1.5. |
| Claim: | 10. A formulation according to claim 9 , wherein the fine particle dose less than 3.3 μm is greater than 40% to minimize interpatient variability associated with oropharyngeal deposition. |
| Claim: | 11. A formulation according to claim 9 , wherein variability in the fraction of particles with a d2Q <500 (expressed as the mean variability) is less than 20% across a range of pressure drops in a dry powder inhaler from 2 kPa to 6 kPa. |
| Claim: | 12. A formulation according to claim 9 , wherein the mass ratio of first active ingredient or the second active ingredient or any optional third active ingredient in the fine particle dose is within 10% of the ratio of the nominal doses of the drugs. |
| Claim: | 13. A delivery system, comprising an inhaler and a dry powder formulation for inhalation according to claim 1 . |
| Patent References Cited: | 736102 August 1903 Howe 6309623 October 2001 Weers et al. 6565885 May 2003 Tarara et al. 6638495 October 2003 Weers et al. 7172752 February 2007 Watanabe et al. 7306787 December 2007 Tarara et al. 7326691 February 2008 Duddu et al. 7442388 October 2008 Weers et al. 2003/0108743 June 2003 Anderson 2004/0028619 February 2004 Watanabe et al. 2004/0105820 June 2004 Weers et al. 2005/0003004 January 2005 Vehring et al. 2005/0048127 March 2005 Brown et al. 2005/0148563 July 2005 Cuss et al. 2008/0085315 April 2008 Doney et al. 2010/0016597 January 2010 Hirokawa et al. 2010/0120737 May 2010 Feth et al. 2 623 560 August 2008 101342155 January 2009 1322301 July 2003 2007-277057 October 2007 9964014 December 1999 0027363 May 2000 01/76575 October 2001 01/85137 November 2001 02/15876 February 2002 02/28378 April 2002 0245682 June 2002 03/035051 May 2003 03/068944 October 2003 2004/060351 July 2004 2004/098561 November 2004 2004/110404 December 2004 2006010921 February 2006 2007/009164 January 2007 2007/011989 January 2007 2007/077219 July 2007 2007/135409 November 2007 2008/014478 January 2008 2008/066298 June 2008 |
| Other References: | Friedman et al “A retrospective study of the use of fluticasone propionate/salmeterol combination as initial asthma controller therapy in a commercially insured population” Clin. Ther., Excerpta Medica, vol. 30, No. 10, 2008. cited by applicant Beier et al “Safety, tolerability and indaceterol, a novel once-daily beta2-agonists, in patents with COPD: a 28 day randomized, placebo controlled clinical trial” Pulm. Pharmacol. & Thera., vol. 20, No. 6, 2007. cited by applicant Borgstrom et al , Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects. Eur Resp J. 1994, 7:69-73. cited by applicant EMA ICH Topic Q3C Impurities: Guideline for Residual solvents. cited by applicant |
| Primary Examiner: | Weddington, Kevin E |
| Attorney, Agent or Firm: | Woods, Daniel |
| Accession Number: | edspgr.09050267 |
| Database: | USPTO Patent Grants |
| Language: | English |
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