US 11,737,989 B2
Clevidipine nanoparticles and pharmaceutical compositions thereof
Rajeshwar Motheram, Dayton, NJ (US); David C. Hanley, Sr., Brookfield, CT (US); Akif Emre Tureli, Saarlouis (DE); and Monika Kanter, Saarburg (DE)
Assigned to CHIESI FARMACEUTICI S.P.A., Parma (IT)
Appl. No. 15/312,461
Filed by CHIESI Farmaceutici S.p.A., Parma (IT)
PCT Filed May 19, 2015, PCT No. PCT/US2015/031470
§ 371(c)(1), (2) Date Nov. 18, 2016,
PCT Pub. No. WO2015/179334, PCT Pub. Date Nov. 26, 2015.
Claims priority of provisional application 62/000,119, filed on May 19, 2014.
Prior Publication US 2017/0087093 A1, Mar. 30, 2017
Int. Cl. A61K 9/51 (2006.01); A61K 9/00 (2006.01); A61K 31/4422 (2006.01); A61K 47/10 (2017.01)
CPC A61K 9/5123 (2013.01) [A61K 9/0019 (2013.01); A61K 31/4422 (2013.01); A61K 47/10 (2013.01)] 24 Claims
OG exemplary drawing
 
1. A method of making a therapeutic nanoparticle, comprising clevidipine, or a pharmaceutically acceptable salt thereof and at least one excipient, said method comprising:
dissolving clevidipine, or a pharmaceutically acceptable salt thereof, in a first solvent to form a solution,
pumping the solution comprising clevidipine, or pharmaceutically acceptable salt thereof, through heated capillaries into a heated microjet reactor,
precipitating the solution with a second solvent using the microjet reactor, and
removing a portion of the solvents forming a core portion and an outer portion of said nanoparticle;
wherein the core portion comprises the clevidipine or pharmaceutically acceptable salt thereof, and the outer portion surrounds the core and comprises the at least one excipient,
wherein the at least one excipient is present in the first solvent and/or the second solvent,
wherein the at least one excipient is selected from the group consisting of water insoluble excipients, water soluble excipients and combinations thereof,
wherein said water soluble excipient is polyethylene glycol 200 (PEG 200), sodium deoxycholate, vitamin E tocopheryl polyethylene glycol succinate (vitamin E TPGS) or combinations thereof,
wherein said water insoluble excipient is vitamin E, deoxycholic acid, phosphotidylcholine or combinations thereof, and
storing the nanoparticle for at least three months at room temperature and the level of any single impurity is no more than 1.8% on a weight-to-weight basis.