US 11,717,481 B2
Reduction of flake-like aggregation in nanoparticulate active agent compositions
Niels P. Ryde, Malvern, PA (US); Peter Snyder, King of Prussia, PA (US); Wei Liu, Exton, PA (US); and David M. Slifer, Downingtown, PA (US)
Assigned to ALKERMES PHARMA IRELAND LIMITED, Dublin (IE)
Filed by Alkermes Pharma Ireland Limited, Dublin (IE)
Filed on Dec. 3, 2021, as Appl. No. 17/542,276.
Application 14/133,191 is a division of application No. 12/788,196, filed on May 26, 2010, abandoned.
Application 17/542,276 is a continuation of application No. 15/971,616, filed on May 4, 2018, granted, now 11,253,478.
Application 15/971,616 is a continuation of application No. 15/130,255, filed on Apr. 15, 2016, granted, now 9,974,746.
Application 15/130,255 is a continuation of application No. 14/133,191, filed on Dec. 18, 2013, granted, now 9,345,665.
Claims priority of provisional application 61/181,641, filed on May 27, 2009.
Prior Publication US 2022/0211626 A1, Jul. 7, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/16 (2006.01); A61K 9/00 (2006.01); A61K 9/14 (2006.01); A61K 31/5415 (2006.01); A61K 9/10 (2006.01); A61K 47/02 (2006.01); A61K 47/10 (2017.01); A61K 47/26 (2006.01); A61K 47/28 (2006.01); A61K 47/32 (2006.01)
CPC A61K 9/1623 (2013.01) [A61K 9/0019 (2013.01); A61K 9/10 (2013.01); A61K 9/145 (2013.01); A61K 9/146 (2013.01); A61K 9/1617 (2013.01); A61K 9/1635 (2013.01); A61K 9/1688 (2013.01); A61K 31/5415 (2013.01); A61K 47/02 (2013.01); A61K 47/10 (2013.01); A61K 47/26 (2013.01); A61K 47/28 (2013.01); A61K 47/32 (2013.01)] 40 Claims
 
1. An injectable meloxicam composition substantially free of metals produced by a method comprising:
(a) preparing a dispersion of a liquid dispersion media, meloxicam and at least one surface stabilizer to form a meloxicam dispersion;
(b) milling the meloxicam dispersion in the presence of a grinding media, wherein the grinding media comprises polymeric or copolymeric resin beads and is substantially free of metals to form a meloxicam nanoparticle dispersion;
(c) adding a flake-like aggregation reducing agent to the meloxicam nanoparticle dispersion of step (b), wherein the flake-like aggregation reducing agent is selected from the group consisting of sucrose, mannitol and dextrose; and
(d) separating out the grinding media to thereby form the injectable meloxicam composition substantially free of metals;
wherein the meloxicam particles in the injectable meloxicam composition have an effective average particle size of less than about 300 nm, and no more than 6,000 meloxicam particles are greater than 10 μm and no more than 600 meloxicam particles are greater than 25 μm.