US 12,414,919 B2
Method for preparing biocompatible polymer-based apixaban-loaded microspheres
Dooyong Jeong, Gyeonggi-do (KR); Sang-Hwi Lee, Gyeonggi-do (KR); Mijung Kim, Gyeonggi-do (KR); Ye-Ji Kim, Ulsan (KR); and Jae Hyung Park, Seoul (KR)
Assigned to HLB PHARMACEUTICAL CO., LTD., (KR)
Appl. No. 17/598,495
Filed by HLB PHARMACEUTICAL CO., LTD., Gyeonggi-do (KR)
PCT Filed Mar. 20, 2020, PCT No. PCT/KR2020/003885
§ 371(c)(1), (2) Date Sep. 27, 2021,
PCT Pub. No. WO2020/197190, PCT Pub. Date Oct. 1, 2020.
Claims priority of application No. 10-2019-0035355 (KR), filed on Mar. 27, 2019.
Prior Publication US 2022/0183978 A1, Jun. 16, 2022
Int. Cl. A61K 9/16 (2006.01); A61K 9/00 (2006.01); A61K 31/4545 (2006.01)
CPC A61K 9/1682 (2013.01) [A61K 9/0019 (2013.01); A61K 9/1617 (2013.01); A61K 31/4545 (2013.01)] 5 Claims
 
1. A method for preparing biocompatible polymer-based Apixaban-loaded microspheres for sustained release injectable formulation, the method comprising:
i) adding a fatty acid or triglyceride to a dispersed phase comprising Apixaban or a pharmaceutically acceptable salt thereof, a biocompatible polymer and a halogenated organic solvent; and
ii) preparing biocompatible polymer-based Apixaban-loaded microspheres for sustained release injectable formulation using a microfluidic method,
wherein the formation of Apixaban crystals is inhibited by addition of the fatty acid or triglyceride;
wherein the dispersed phase comprises Apixaban or the pharmaceutically acceptable salt thereof in an amount of 10% to 50% by weight relative to the biocompatible polymer, comprises the fatty acid or triglyceride in an amount of 50% by weight or less relative to the biocompatible polymer, and comprises the biocompatible polymer in an amount of 5 (w/v) % to 30 (w/v) % relative to the halogenated organic solvent,
the biocompatible polymer is any one or more selected from the group consisting of polylactic-co-glycolic acid (PLGA), polylactic acid (PLA), and polycaprolactone (PCL), and
the Apixaban-loaded microsphere comprises 5% to 30% by weight of Apixaban relative to the total weight of the Apixaban-loaded microsphere.