Evaporation-triggered nanoprecipitation for PLGA nanoparticle formation using a spinning-disc system

Abstract

Researchers have successfully introduced many formulations based on nanoparticles and many of those products are already available for clinical use. When it comes to polymeric nanoparticles, there are only natural polymers (e.g., albumin) approved but several publications describe very promising results at the laboratory level. Poly (lactic-co-glycolic acid) (PLGA) is widely used by researchers to prepare nanoparticles and there are several publications available with very promising results at the laboratory level but there are barely any approaches for commercial production of PLGA nanoparticles. One of the main challenges is the difficulty in converting lab scale production into commercial scale production. This study describes a very innovative manufacturing technology i.e. spinning disc system (SDS) for the continuous manufacturing of PLGA nanoparticles. It relies on a one-pot process, i.e. polymer, organic phase, aqueous phase and drug are homogeneously distributed and mixing as critical process parameter is eliminated. Centrifugal force causes the solution to spread all over the rotating disc and the large surface area of the disc facilitates the evaporation of the organic phase resulting in polymer precipitation. This manufacturing method also enables tuning of particle size (a wide range of between 120 and 320 nm can be achieved). Compared to standard bench top (BT) methods, smaller particles with higher yields were obtained (141 nm with a yield of 89 %). Along with continuous production of nanoparticles, SDS also improves encapsulation efficiency and drug loading of PLGA nanoparticles. Curcumin (CUR) as a model drug substance was encapsulated with SDS with a high encapsulation efficiency (60–70 %) compared to only 10–25 % in BT. Subsequently, a drug loading twice as high as with BT was achieved using SDS. The nanoparticles prepared with or without stabilizer produced nearly monodisperse particle sizes (PDI <0.1) and showed negative zeta-potentials (<−30 mV), which showed promising colloidal stability over a test period of 28 days. Maximum 7.4 nm of deviation from initial size was observed in stability studies.