Analysis of Process Parameters Affecting Spray-Dried Oily Core Nanocapsules Using Factorial Design

The purpose of this work was to optimize the process parameters required for the production of spray-dried oily core nanocapsules (NCs) with targeted size and drug yield using a two-level four-factor fractional factorial experimental design (FFED). The coded process parameters chosen were inlet temperature (X1), feed flow rate (X2), atomizing air flow (X3), and aspiration rate (X4). The produced NCs were characterized for size, yield, morphology, and powder flowability by dynamic light scattering, electron microscope, Carr’s index, and Hausner ratio measurement, respectively. The mean size of produced NCs ranged from 129.5 to 444.8 nm, with yield varying from 14.1% to 31.1%. The statistical analysis indicated an adequate model fit in predicting the effect of process parameters affecting yield. Predicted condition for maximum yield was: inlet temperature 140°C, atomizing air flow 600 L/h, feed flow rate 0.18 L/h, and aspiration air flow set at 100%, which led to a yield of 30.8%. The morphological analysis showed the existence of oily core and spherical nanostructure. The results from powder flowability analysis indicated average Carr’s index and Hausner ratio of 42.77% and 1.76, respectively. Spray-dried oily core NCs with size lower than 200 nm were successfully produced, and the FFED proved to be an effective approach in predicting the production of spray-dried NCs of targeted yield

Spray-dried polyelectrolyte microparticles in oral antigen delivery : stability, biocompatibility and cellular uptake

During the past decade, extensive research has undeniably improved the formulation and delivery of oral vaccines. Nevertheless, several factors, such as the harsh gastrointestinal environment together with tolerance induction to exogenous antigens, have thus far impeded the optimal effectiveness and clinical application of oral delivery systems. The current study encompasses an initial evaluation of the stability, biocompatibility and cellular uptake of two promising candidate systems for oral antigen delivery, i.e. calcium carbonate- (CP) and mannitol-templated (MP) porous microspheres. Both spray-dried formulations were efficiently internalized by human intestinal epithelial cells (Caco-2 and HT-29) and degraded into phagolysosomal intracellular compartments. In addition, cellular particle uptake and processing significantly up-regulated the expression of (HLA) class-II and costimulatory molecules on intestinal epithelial cells. Even though the high surface-area-to-volume ratio of the microspheres were expected to favor protease access, antigen release was remarkably limited in simulated intestinal fluid and was even absent under gastric conditions. Finally, CP nor MP exerted cytotoxicity upon prolonged in vitro incubation with high antigen concentration. Altogether, these data support the potential of CP and MP for oral antigen delivery and motivate the further development of these promising carrier systems in in vivo studies