FDA-Akina joint publication describes solvent-vapor particle-morphological testing methodology for microstructural analysis

 

Long-Acting Injectable (LAI) delivery microparticles are complicated structures comprised of both biodegradable polymers, pharmaceutical compounds, and other excipients in a specific configuration so as to achieve the desired delivery profile. These allow for single injections to provide patients with the quantity of drug necessary for pharmaceutical efficacy from weeks up to six-months based on the formulation. Accomplishing this is not a trivial task and, due to their small size, obtaining critical information regarding the nature of the microstructural arrangement of the various components within the particles. To do this, the various components must be selectively altered or removed and the particle analyzed in order to record the change. Recently, Akina’s lab, in cooperation with the Food and Drug Administration via the GDUFA program, developed a methodology to selectively expose particles to semi-solvent vapors and record their changes. This methodology can enable learning more about the structural arrangements within microparticle formulations. Want to learn more about your prototype particles, see more about this and other analysis options here (http://www.akinalytics.com/index.php#home). Read more: Garner, John, Sarah Skidmore, Justin Hadar, Haesun Park, Kinam Park, Bin Qin, and Yan Wang. "Surface analysis of sequential semi-solvent vapor impact (SAVI) for studying microstructural arrangements of poly (lactide-co-glycolide) microparticles." Journal of Controlled Release 350 (2022): 600-612. http://kinampark.com/KPYear/files/2022%20Garner%2C%20Surface%20analysis%20of%20sequential%20semi-solvent%20vapor%20impact%20%28SAVI%29%20for%20studying%20microstructural%20arrangements%20of%20poly%28lactide-co-glycolide%29%20microparticles.pdf

“Abstract: Biodegradable poly(lactide-co-glycolide) (PLGA) microparticles have been used as long-acting injectable (LAI) drug delivery systems for more than three decades. Despite extensive use, few tools have been available to examine and compare the three-dimensional (3D) structures of microparticles prepared using different compositions and processing parameters, all collectively affecting drug release kinetics. Surface analysis after sequential semi-solvent impact (SASSI) was conducted by exposing PLGA microparticles to different semi-solvent in the liquid phase. The use of semi-solvent liquids presented practical experimental difficulties, particularly in observing the same microparticles before and after exposure to semi-solvents. The difficulties were overcome by using a new sequential semi-solvent vapor (SSV) method to examine the morphological changes of the same microparticles. The SASSI method based on SSV is called surface analysis of semi-solvent vapor impact (SAVI). Semi-solvents are the solvents that dissolve PLGA polymers depending on the polymer's lactide:glycolide (L:G) ratio. A sequence of semi-solvents was used to dissolve portions of PLGA microparticles in an L:G ratio-dependent manner, thus revealing different structures depending on how microparticles were prepared. Exposing PLGA microparticles to semi-solvents in the vapor phase demonstrated significant advantages over using semi-solvents in the liquid phase, such as in control of exposure conditions, access to imaging, decreasing the time for sequential exposure of semi-solvents, and using the same microparticles. The SSV approach for morphological analysis provides another tool to enhance our understanding of the microstructural arrangement of PLGA polymers. It will improve our comprehensive understanding of the factors controlling drug release from LAI formulations based on PLGA polymers. (This work was supported by BAA Contract # 75F40119C10096 from the U.S. Food and Drug Administration (FDA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the FDA)”