2023 FDA Science Forum
Qualitative and quantitative analysis of lipids in Exparel® injectable liposomal drug formulation
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Contributing OfficeOffice of Regulatory Affairs
Abstract
Application of liposomal formulations in drug delivery has gained popularity because of distinct advantages over traditional drug formulations in altered drug distribution, sustained delivery, and others. Exparel® is a multivesicular liposomal formulation (MVL) of bupivacaine, which provides sustained release at the site of injection resulting in prolong anesthetic effect. MVL possesses a unique structural assembly of multiple polyhedral chambers separated by lipid septal, providing prolonged release following the in vivo erosion of lipid membranes. Compared to univesicular liposomes, MVL use charge neutral triacylglycerols which serve as space fillers at the lipid membrane intersection, leading to structural stability of the MVLs. As the lipid composition leads to its unique structure, the quantification of major lipid constituents and identification of possible minor lipids, lipid degradation products, and cholesterol oxidation products are necessary for a complete evaluation of the formulation. We utilized a novel UHPLC-ESI-QTOF method and SimLipid® high throughput lipid identification software to identify and quantify all the major and minor lipids, cholesterol oxidation products, the active pharmaceutical ingredient (API) and its enantiomers in two batches of commercially available Exparel® injectable liposomal drug formulation. We identified 24 minor lipids and two cholesterol oxidation products in the formulation. Out of the 24 minor lipids identified, 22 were phospholipids and the others were triacylglycerols. The two batches of Exparel® were found to contain 4.264% and 3.699% of minor lipids content as compared to the total amounts of lipids. This approach has allowed us to analyze the major and minor lipid excipient content of an MVL drug formulation and could be used for comparison of different Exparel® batches as well as future generic and brand product comparison.
