US 11,925,706 B2
Manufacturing of bupivacaine multivesicular liposomes
Jeffrey S. Hall, San Diego, CA (US); David J. Turnbull, San Diego, CA (US); John J. Grigsby, Jr., San Diego, CA (US); Soroush M. Ardekani, San Diego, CA (US); and Kathleen D. A. Los, San Diego, CA (US)
Assigned to Pacira Pharmaceuticals, Inc., San Diego, CA (US)
Filed by Pacira Pharmaceuticals, Inc., San Diego, CA (US)
Filed on May 30, 2023, as Appl. No. 18/325,924.
Application 18/325,924 is a continuation of application No. 17/719,716, filed on Apr. 13, 2022.
Application 17/719,716 is a continuation of application No. 17/536,516, filed on Nov. 29, 2021, granted, now 11,304,904.
Application 17/536,516 is a continuation of application No. 17/319,591, filed on May 13, 2021, granted, now 11,185,506, issued on Nov. 30, 2021.
Application 17/319,591 is a continuation of application No. 17/156,400, filed on Jan. 22, 2021, granted, now 11,033,495, issued on Jun. 15, 2021.
Prior Publication US 2023/0293435 A1, Sep. 21, 2023
Int. Cl. A61K 9/127 (2006.01); A61K 31/451 (2006.01); B01D 61/14 (2006.01); B01F 23/41 (2022.01); B01F 23/80 (2022.01); B01F 101/22 (2022.01)
CPC A61K 9/1277 (2013.01) [A61K 31/451 (2013.01); B01D 61/146 (2022.08); B01D 61/147 (2013.01); B01D 61/1471 (2022.08); B01F 23/4105 (2022.01); B01F 23/808 (2022.01); B01D 2315/10 (2013.01); B01D 2315/16 (2013.01); B01F 23/4144 (2022.01); B01F 23/4145 (2022.01); B01F 2101/22 (2022.01); B01F 2215/044 (2013.01); B01F 2215/0477 (2013.01); B01F 2215/0481 (2013.01)] 29 Claims
OG exemplary drawing
 
1. A composition of bupivacaine encapsulated multivesicular liposomes (MVLs), comprising:
bupivacaine encapsulated MVLs comprising bupivacaine residing inside a plurality of internal aqueous chambers of MVLs separated by lipid membranes, wherein the lipid membranes comprise 1, 2-dierucoylphosphatidylcholine (DEPC), 1, 2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG), cholesterol, and at least one neutral lipid, the plurality of internal aqueous chambers of the MVLs also comprise lysine; and
an aqueous medium in which the bupivacaine encapsulated MVLs are suspended, wherein the aqueous medium also comprises unencapsulated bupivacaine;
wherein the bupivacaine concentration in the composition is from about 11.3 mg/mL to about 17.0 mg/mL;
wherein an erucic acid concentration in the composition is about 53 μg/mL or less when measured after the composition is stored at 25° C. for three months, and the erucic acid concentration in the composition is about 99 μg/mL or less when measured after the composition is stored at 25° C. for six months; and
wherein the encapsulated lysine concentration in the composition is at least about 0.03 mg/mL.