TY - JOUR
T1 - Impact of media material and process parameters on breakage kinetics–energy consumption during wet media milling of drugs
AU - Parker, Nathaniel
AU - Rahman, Mahbubur
AU - Bilgili, Ecevit
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/8
Y1 - 2020/8
N2 - While crosslinked polystyrene (CPS) beads and yttrium-stabilized zirconia (YSZ) beads have been commonly used as media for wet milling of poorly soluble drugs and their dissolution enhancement, no first-principle rationale exists for selecting the bead material. The aim of this study is to investigate the impact of stirrer speed (2000–4000 rpm) and CPS bead loading (~20–60%) on the breakage kinetics–energy consumption during milling of griseofulvin, a model poorly soluble drug, and compare the performance of CPS vs. YSZ at the highest bead loading. Laser diffraction, SEM, rheological analysis, and XRPD were used for characterization. The milling was most effective at the highest bead loading–stirrer speed. A microhydrodynamic model suggests that an increase in stirrer speed led to faster breakage due to more frequent and forceful CPS bead–bead collisions. Despite causing slight decrease in maximum contact pressure, an increase in CPS bead loading caused a dramatic increase in average frequency of drug particle compressions, which dominated the faster breakage observed. While YSZ generally required higher specific energy consumption than CPS, it achieved the same product fineness faster than CPS. The microhydrodynamic model rationalized the favorable use of YSZ over CPS beads within the experimental domain studied.
AB - While crosslinked polystyrene (CPS) beads and yttrium-stabilized zirconia (YSZ) beads have been commonly used as media for wet milling of poorly soluble drugs and their dissolution enhancement, no first-principle rationale exists for selecting the bead material. The aim of this study is to investigate the impact of stirrer speed (2000–4000 rpm) and CPS bead loading (~20–60%) on the breakage kinetics–energy consumption during milling of griseofulvin, a model poorly soluble drug, and compare the performance of CPS vs. YSZ at the highest bead loading. Laser diffraction, SEM, rheological analysis, and XRPD were used for characterization. The milling was most effective at the highest bead loading–stirrer speed. A microhydrodynamic model suggests that an increase in stirrer speed led to faster breakage due to more frequent and forceful CPS bead–bead collisions. Despite causing slight decrease in maximum contact pressure, an increase in CPS bead loading caused a dramatic increase in average frequency of drug particle compressions, which dominated the faster breakage observed. While YSZ generally required higher specific energy consumption than CPS, it achieved the same product fineness faster than CPS. The microhydrodynamic model rationalized the favorable use of YSZ over CPS beads within the experimental domain studied.
KW - Breakage kinetics
KW - Milling media
KW - Nanoparticles
KW - Poorly soluble drugs
KW - Process modeling
KW - Wet stirred media milling
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U2 - 10.1016/j.ejpb.2020.05.024
DO - 10.1016/j.ejpb.2020.05.024
M3 - Article
C2 - 32522681
AN - SCOPUS:85086404595
SN - 0939-6411
VL - 153
SP - 52
EP - 67
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -