US 12,290,600 B2
Methods for continuous manufacture of liposomal drug products
Robert Worsham, Bridgewater, NJ (US)
Assigned to Insmed Incorporated, Bridgewater, NJ (US)
Filed by INSMED INCORPORATED, Bridgewater, NJ (US)
Filed on Dec. 30, 2022, as Appl. No. 18/091,492.
Application 18/091,492 is a continuation of application No. 16/981,149, granted, now 11,571,386, previously published as PCT/US2019/024901, filed on Mar. 29, 2019.
Claims priority of provisional application 62/650,372, filed on Mar. 30, 2018.
Prior Publication US 2023/0218529 A1, Jul. 13, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/127 (2006.01); A61K 9/1277 (2025.01); A61K 31/145 (2006.01); A61K 31/4174 (2006.01); A61K 31/4196 (2006.01); A61K 31/42 (2006.01); A61K 31/4375 (2006.01); A61K 31/496 (2006.01); A61K 31/5025 (2006.01); A61K 31/505 (2006.01); A61K 31/65 (2006.01); A61K 31/7036 (2006.01); A61K 31/7048 (2006.01); A61K 38/14 (2006.01); B01F 23/41 (2022.01); B01F 101/22 (2022.01)
CPC A61K 9/1277 (2013.01) [A61K 31/145 (2013.01); A61K 31/4174 (2013.01); A61K 31/4196 (2013.01); A61K 31/42 (2013.01); A61K 31/4375 (2013.01); A61K 31/496 (2013.01); A61K 31/5025 (2013.01); A61K 31/505 (2013.01); A61K 31/65 (2013.01); A61K 31/7036 (2013.01); A61K 31/7048 (2013.01); A61K 38/14 (2013.01); B01F 23/4105 (2022.01); B01F 2101/22 (2022.01)] 21 Claims
 
1. A method for continuously manufacturing a liposomal active pharmaceutical ingredient (API) formulation, comprising;
mixing a lipid solution comprising a lipid dissolved in an organic solvent with an aqueous API solution, wherein the lipid solution and aqueous API solution are mixed from two separate streams in an in-line fashion, and wherein a liposomal encapsulated API is formed at the intersection of the two streams, introducing the liposomal encapsulated API into a first central vessel comprising an inlet and an outlet, through the inlet, wherein the outlet is in fluid communication with an inlet of a first tangential flow filtration (TFF) unit comprising the inlet and a firstand second outlet, wherein the first outlet of the first TFF unit is in fluid communication with an inlet of a second TFF unit comprising the inlet and a first and second outlet, and the second outlet of the first TFF unit is a waste outlet; and wherein the first outlet of the second TFF unit is a retentate outlet and the second outlet of the second TFF unit is a waste outlet;
flowing the liposomal encapsulated API into the first TFF unit for a first period of time, wherein the liposomal encapsulated API enters the first TFF unit through the inlet of the first TFF unit and exits through the first outlet of the first TFF unit;
flowing the liposomal encapsulated API from the first outlet of the first TFF unit through the inlet of the second TFF unit for a second period of time; and
collecting the liposomal API formulation from the first outlet of the second TFF unit, wherein the liposomal encapsulated API is subjected to continuous in-line diafiltration via TFF prior to collecting the liposomal API formulation.