TY - JOUR
T1 - Use of Bead Mixtures as a Novel Process Optimization Approach to Nanomilling of Drug Suspensions
AU - Guner, Gulenay
AU - Kannan, Manisha
AU - Berrios, Matthew
AU - Bilgili, Ecevit
N1 - Funding Information:
The authors thank Nisso for providing the materials free of charge. The corresponding author (E.B.) thanks Professor Dmitry Eskin for fruitful discussion on the microhydrodynamic model. G.G. acknowledges the NJIT Department of Chemical and Materials Engineering for the financial support, while E.B. acknowledges the Faculty Instrument Usage Seed Grant (FIUSG) by NJIT Otto H. York Center & the Materials Characterization Lab for characterization support. The authors report no conflict of interest.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: We aimed to evaluate the feasibility of cross-linked polystyrene (CPS)–yttrium-stabilized zirconia (YSZ) bead mixtures as a novel optimization approach for fast, effective production of drug nanosuspensions during wet stirred media milling (WSMM). Methods: Aqueous suspensions of 10% fenofibrate (FNB, drug), 7.5% HPC-L, and 0.05% SDS were wet-milled at 3000–4000 rpm and 35%–50% volumetric loading of CPS:YSZ bead mixtures (CPS:YSZ 0:1–1:0 v:v). Laser diffraction, SEM, viscometry, DSC, and XRPD were used for characterization. An nth-order model described the breakage kinetics, while a microhydrodynamic model allowed us to gain insights into the impact of bead materials. Results: CPS beads achieved the lowest specific power consumption, whereas YSZ beads led to the fastest breakage. Breakage followed second-order kinetics. Optimum conditions were identified as 3000 rpm and 50% loading of 0.5:0.5 v/v CPS:YSZ mixture from energy–cycle time–heat dissipation perspectives. The microhydrodynamic model suggests that YSZ beads experienced more energetic/forceful collisions with smaller contact area as compared with CPS beads owing to the higher density–elastic modulus of the former. Conclusions: We demonstrated the feasibility of CPS–YSZ bead mixtures and rationalized its optimal use in WSMM through their modulation of breakage kinetics, energy utilization, and heat dissipation.
AB - Purpose: We aimed to evaluate the feasibility of cross-linked polystyrene (CPS)–yttrium-stabilized zirconia (YSZ) bead mixtures as a novel optimization approach for fast, effective production of drug nanosuspensions during wet stirred media milling (WSMM). Methods: Aqueous suspensions of 10% fenofibrate (FNB, drug), 7.5% HPC-L, and 0.05% SDS were wet-milled at 3000–4000 rpm and 35%–50% volumetric loading of CPS:YSZ bead mixtures (CPS:YSZ 0:1–1:0 v:v). Laser diffraction, SEM, viscometry, DSC, and XRPD were used for characterization. An nth-order model described the breakage kinetics, while a microhydrodynamic model allowed us to gain insights into the impact of bead materials. Results: CPS beads achieved the lowest specific power consumption, whereas YSZ beads led to the fastest breakage. Breakage followed second-order kinetics. Optimum conditions were identified as 3000 rpm and 50% loading of 0.5:0.5 v/v CPS:YSZ mixture from energy–cycle time–heat dissipation perspectives. The microhydrodynamic model suggests that YSZ beads experienced more energetic/forceful collisions with smaller contact area as compared with CPS beads owing to the higher density–elastic modulus of the former. Conclusions: We demonstrated the feasibility of CPS–YSZ bead mixtures and rationalized its optimal use in WSMM through their modulation of breakage kinetics, energy utilization, and heat dissipation.
KW - bead mixtures
KW - poorly water-soluble drugs
KW - process modeling
KW - process optimization
KW - wet stirred media milling
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U2 - 10.1007/s11095-021-03064-2
DO - 10.1007/s11095-021-03064-2
M3 - Article
C2 - 34169438
AN - SCOPUS:85108619909
SN - 0724-8741
VL - 38
SP - 1279
EP - 1296
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 7
ER -