A comparative assessment of continuous production techniques to generate sub-micron size PLGA particles

Publication date: Available online 23 August 2018Source: International Journal of PharmaceuticsAuthor(s): Maria Camilla Operti, David Fecher, Eric A.W. van Dinther, Silko Grimm, Rima Jaber, Carl G. Figdor, Oya TagitAbstractThe clinical and commercial development of polymeric sub-micron size formulations based on poly(lactic-co-glycolic acid) (PLGA) particles is hampered by the challenges related to their good manufacturing practice (GMP)-compliant, scale-up production without affecting the formulation specifications. Continuous process technologies enable large-scale production without changing the process or formulation parameters by increasing the operation time. Here, we explore three well-established process technologies regarding continuity for the large-scale production of sub-micron size PLGA particles developed at the lab scale using a batch method. We demonstrate optimization of critical process and formulation parameters for high-shear mixing, high-pressure homogenization and microfluidics technologies to obtain PLGA particles with a mean diameter of 150 nm – 250 nm and a small polydispersity index (PDI, ≤ 0.2). The most influential parameters on the particle size distribution are discussed for each technique with a critical evaluation of their suitability for GMP production. Although each technique can provide the desired particle size distribution, high-shear mixing is found to be particularly promising due to the availability of GMP-ready equipment and large ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research