Break
AIChE Annual Meeting
2018
2018 AIChE Annual Meeting
2018 International Congress on Energy
USA-China Progress in Biomass Conversion Technology II
Wednesday, October 31, 2018 - 1:30pm to 1:50pm
Laser diffraction results show that 2.5% HPC SLâ0.2% SDS led to the finest ITZ nanosuspension, whereas without SDS, only 4.5% HPC with SL/L grades ensured minimal aggregation. Rheological characterization reveals that aggregated suspensions exhibited pronounced pseudoplasticity, whereas stable suspensions exhibited near Newtonian behavior. Wet-milled stable 10% ITZ nanosuspensions exhibiting near-Newtonian flow behavior were prepared with 4.5% HPC SL/L (100 and 140 kg/mol MW, respectively). At this concentration, HPC SSL (40 kg/mol), HPMC E3 (10 kg/mol), and PVP K30 (50 kg/mol) could not suppress ITZ nanoparticle aggregation, leading to significant pseudoplastic behavior. Contrary to previous studies that highlight the favorability of low MW polymers [3,4] (specifically <50 kg/mol for ITZâHPC [3]), our study demonstrated that higher MW HPC (100 and 140 kg/mol) is more favorable for ITZ nanosuspension stabilization, which in line with the thermodynamic considerations of polymer adsorption. Unfortunately, studies like [3,4] that used low-energy mills do not truly reflect the impact of different polymers or MW on steric stabilization and reduction of drug aggregate formation. The use of higher MW polymer and/or higher polymer concentration causes more pronounced viscous dampening [5], which slows down the breakage in low-energy mills more profoundly than in high-energy mills like wet stirred media mills used in this study. Hence, such studies drew somewhat confounded conclusions about the impact of polymer MW due to pronounced impact of viscous dampening. Not only did high-energy, wet stirred media milling enabled faster production of ITZ nanoparticles than low energy mills used in ref. [3] for ITZâHPC, but also it allowed us to elucidate the role of polymer MW in stabilization of drug nanoparticles, which in line with the thermodynamic consideration of polymer adsorption. Although higher MW HPC led to better stabilization of the ITZ nanosuspensions here, the use of HPC with MW >140 kg/mol could cause more pronounced viscous dampening and ensuing slower breakage. Hence, overall our results point out the criticality of choosing optimal polymer MW in the stabilization of wet-milled drug nanoparticles and invalidity of the commonly-held notion that low-MW polymers are more effective than high-MW polymers for the stabilization of drug nanosuspensions.
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