title: Micro-Flow Imaging as a quantitative tool to assess size and agglomeration of PLGA microparticles.
abstract: The purpose of this study was to explore the potential of flow imaging microscopy to measure particle size and agglomeration of poly(lactic-co-glycolic acid) (PLGA) microparticles. The particle size distribution of pharmaceutical PLGA microparticle products is routinely determined with laser diffraction. In our study, we performed a unique side-by-side comparison between MFI 5100 (flow imaging microscopy) and Mastersizer 2000 (laser diffraction) for the particle size analysis of two commercial PLGA microparticle products, i.e., Risperdal Consta and Sandostatin LAR. Both techniques gave similar results regarding the number and volume percentage of the main particle population (28-220μm for Risperdal Consta; 16-124μm for Sandostatin LAR). MFI additionally detected a 'fines' population (<28μm for Risperdal Consta; <16μm for Sandostatin LAR), which was overlooked by Mastersizer. Moreover, MFI was able to split the main population into 'monospheres' and 'agglomerates' based on particle morphology, and count the number of particles in each sub-population. Finally, we presented how MFI can be applied in process development of risperidone PLGA microparticles and to monitor the physical stability of Sandostatin LAR. These case studies showed that MFI provides insight into the effect of different process steps on the number, size and morphology of fines, monospheres and agglomerates as well as the extent of microparticle agglomeration after reconstitution. This can be particularly important for the suspendability, injectability and release kinetics of PLGA microparticles.
authors.affiliation: Dr. Reddy's Research & Development B.V., Zernikedreef 12, 2333 CL Leiden, The Netherlands; Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Miranda M C
authors.initials: MMC
authors.lastname: van Beers
authors.affiliation: Dr. Reddy's Research & Development B.V., Zernikedreef 12, 2333 CL Leiden, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Slooten
authors.affiliation: Dr. Reddy's Research & Development B.V., Zernikedreef 12, 2333 CL Leiden, The Netherlands.
authors.forename: Jelte
authors.initials: J
authors.lastname: Meulenaar
authors.affiliation: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Ahmad S
authors.initials: AS
authors.lastname: Sediq
authors.affiliation: Dr. Reddy's Research & Development B.V., Zernikedreef 12, 2333 CL Leiden, The Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: Verrijk
authors.affiliation: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: w.jiskoot@lacdr.leidenuniv.nl.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
mesh_terms: D007091:Image Processing, Computer-Assisted / Q000379:methods*; D019344:Lactic Acid / Q000032:analysis / Q000737:chemistry*; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000032:analysis / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Agglomeration; Flow imaging microscopy; Octreotide acetate; PLGA microparticles; Particle size; Risperidone