Optimization of spray drying by factorial design for production of hollow microspheres for ultrasound imaging

Abstract

A process for producing hollow microcapsules as ultrasound contrast agents was optimized using a 2(3) factorial experimental design method with two replicates. Spray drying, a conveniently scalable encapsulation technique, was used to encapsulate a volatile core material, such as ammonium carbonate, using biodegradable 50-50 poly(D,L-lactide-co-glycolide). Various effects due to changes in processing variables and their interactions were studied using the factorial grid. The high- and low-incremented variables examined included the temperature difference between the inlet and outlet of the spray dryer (5 degrees and 15 degrees C), air atomization pressure (80 and 100 psi), and polymer concentration in solvent (0.005 and 0.025 g/mL). Responses analyzed for computing the main effects and interactions were microcapsule morphology, yield, mean size, and zeta potential. Experimental results showed that polymer concentration was most important for determining microcapsule morphology. The temperature difference for drying prominently affected mean size, and atomization pressure was the main effect for microcapsule yield. Interactions among variables were not present in this case. The best conditions for producing PLGA microcapsules was a temperature difference of 5 degrees C, an initial polymer concentration of 0.005 g/mL, and an atomization pressure of 80 psi. The microcapsule zeta potentials were unaffected by spray-drying conditions.

Investigating thiol-modification on hyaluronan via carbodiimide chemistry using response surface methodology

“…The derivatization is accomplished by the well-known carbodiimide-based activation [11][12][13] of the carboxyl group of HA with N-(3-dimethylaminopropyl)-N 0 -ethylcarbodiimide hydrochloride (EDC) and N-hydroxylsuccinimide (NHS), followed by its reaction with a disulfide-containing amine. [12][13][14][15][16][17][18][19][20][21] Based on the details of experimental conditions from several published sources, we focused on identifying the relative effects of various reaction parameters or factors. Using the design of experiments (DoE) statistics, involving fractional factorial design (FF) 14,15 and response surface methodology (RSM), [16][17][18] one can effectively design experiments to quantitatively identify the relationship of significant factor(s) that affect the reaction output (response).…”

“…[12][13][14][15][16][17][18][19][20][21] Based on the details of experimental conditions from several published sources, we focused on identifying the relative effects of various reaction parameters or factors. Using the design of experiments (DoE) statistics, involving fractional factorial design (FF) 14,15 and response surface methodology (RSM), [16][17][18] one can effectively design experiments to quantitatively identify the relationship of significant factor(s) that affect the reaction output (response). This enables one to statistically optimize the reaction parameters to yield a desired output, carry out better trade-offs when multiple critical factors are governing the reaction, and minimize variability.…”

Novel manufacturing process of hollow polymer microspheres

“…A second step is then necessary to remove the liquid core. A spray-drying process has been described (Narayan et al, 2001), in which the production of hollow microspheres has been optimized by using a factorial design approach. Solvent evaporation or a freeze-drying method to produce hollow gas-filled microspheres are reported in Sato et al (2003), Jin-Woong et al (2003), Ottoboni (2001) and Crotts and Park (1995).…”

Hybrid micro-particles as a magnetically-guidable decontaminant for cesium-eluted ash slurry

“…We think that this shrinkage of nickel ferrocyanide, which strongly binds the PDDA-coated magnetic nanoparticles, is one of the reasons for the formation of the porous structure of MagCE. Spray dryers have been used to obtain not only dry powders but also hollow capsules17. In terms of avoiding decomposition and the loss of the ferromagnetism of the iron nanoparticles through the preparation of MagCE and the reaction in the alkaline slurry, we used iron nanoparticles on which the surface had been coated with a corrosion-resistant iron oxide layer18.…”