(184h) Particle Jamming upon Administration of Long-Acting Injectable Crystalline Drug Suspensions

Long-acting injectable (LAI) crystalline drug suspensions, administered via intramuscular (IM) or subcutaneous (SC) injection, allow sustained drug release over extended periods (weeks to months) following a single administration, greatly reducing dosing frequency and improving patient adherence. The development of crystalline suspensions requires consideration of multiple critical quality attributes, including physical and chemical stability of the suspension, homogeneous dispersion of particles for content uniformity and dose accuracy, and the ability to easily withdraw the suspension into a syringe and administer the formulation to tissue.

However, significant gaps still exist in establishing tools to appropriately characterize long-acting suspensions, particularly with respect to particle aggregation, sedimentation, and injectability to define an appropriate formulation design space. Here we used monodisperse, spherical polymer microparticles of different sizes and prepared different suspension formulations to study the influence of particle size distribution, particle density, drug loading, suspension viscosity and injection conditions on sedimentation and injectability. Specifically, sedimentation was monitored using in-situ probes, such as EasyViewer and Blaze, which tracked real-time particle size, counts and concentration. Subsequently, injectability was assessed by employing syringe pumps for injections into air or porcine tissue. Additionally, we used fluorescence microscope to capture the particle flow within the syringe body and needle, visualizing the process of particle jamming and analyzing the clogged state. Through parameter sensitivity analysis, we identified the appropriate formulation design space to mitigate particle jamming and ensure injectability of long-acting injectable suspensions.