Bupivacaine liposomal injection is a complex multivesicular liposome (MVL) drug product intended for producing localized postsurgical analgesia over a period of time. The active pharmaceutical ingredient, free bupivacaine base, is encapsulated in a network of internal compartments within the MVL to prolong its release kinetics. As particle size (of both the external lipid vesicles and internal compartments), morphology, drug partitioning between the lipid and aqueous phases, and other formulation parameters may influence the rate of drug release, accurate physicochemical characterization is important. It is theorized that the extent of erosion and/or reorganization of the lipid membranes may influence the morphology as well as the in vitro drug release rate. In order to test this hypothesis, a set of experiments to monitor drug release over a period of a week in a simulated dynamic environment is conducted. Particle size of MVL’s was measured prior to and during release using laser diffraction (LD) and Cryo-scanning electron microscopy (Cryo-SEM). Particle size and morphology was examined at critical time points during release, which revealed changes to the size and shape of both the external and internal compartments. Prior to release testing, the volume mean diameter (D50) was 25.5±1.4 µm, and the MVL size was found to be 23.6±11.5 µm, with internal compartments approximately 1.52 ± 0.44 µm in diameter packed in a space-filling polyhedral arrangement. In vitro dissolution studies indicated a potential initial burst release within 2 hours, which was followed by a more gradual release over 7 days.

Physicochemical characterization and in vitro drug release testing of a multivesicular liposomal bupivacaine formulation

254th National Meeting (2017)

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