PMID- 34371746
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210813
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 13
IP  - 7
DP  - 2021 Jul 10
TI  - Kinetic and Microhydrodynamic Modeling of Fenofibrate Nanosuspension Production 
      in a Wet Stirred Media Mill.
LID - 10.3390/pharmaceutics13071055 [doi]
LID - 1055
AB  - This study examined the impact of stirrer speed and bead material loading on 
      fenofibrate particle breakage during wet stirred media milling (WSMM) via three 
      kinetic models and a microhydrodynamic model. Evolution of median particle size 
      was tracked via laser diffraction during WSMM operating at 3000-4000 rpm with 
      35-50% (v/v) concentration of polystyrene or zirconia beads. Additional 
      experiments were performed at the center points of the above conditions, as well 
      as outside the range of these conditions, in order to test the predictive 
      capability of the models. First-order, nth-order, and warped-time kinetic models 
      were fitted to the data. Main effects plots helped to visualize the influence of 
      the milling variables on the breakage kinetics and microhydrodynamic parameters. 
      A subset selection algorithm was used along with a multiple linear regression 
      model (MLRM) to delineate how the breakage rate constant k was affected by the 
      microhydrodynamic parameters. As a comparison, a purely empirical correlation for 
      k was also developed in terms of the process/bead parameters. The nth-order model 
      was found to be the best model to describe the temporal evolution; nearly 
      second-order kinetics (n  congruent with 2) was observed. When the process was operated at a 
      higher stirrer speed and/or higher loading with zirconia beads as opposed to 
      polystyrene beads, the breakage occurred faster. A statistically significant 
      (p-value </= 0.01) MLRM of three microhydrodynamic parameters explained the 
      variation in the breakage rate constant best (R(2) >/= 0.99). Not only do the 
      models and the nth-order kinetic-microhydrodynamic correlation enable deeper 
      process understanding toward developing a WSMM process with reduced cycle time, 
      but they also provide good predictive capability, while outperforming the purely 
      empirical correlation.
FAU - Guner, Gulenay
AU  - Guner G
AD  - Otto H. York Department of Chemical and Materials Engineering, New Jersey 
      Institute of Technology, Newark, NJ 07102, USA.
FAU - Yilmaz, Dogacan
AU  - Yilmaz D
AD  - Department of Mechanical and Industrial Engineering, New Jersey Institute of 
      Technology, Newark, NJ 07102, USA.
FAU - Bilgili, Ecevit
AU  - Bilgili E
AUID- ORCID: 0000-0002-8880-6783
AD  - Otto H. York Department of Chemical and Materials Engineering, New Jersey 
      Institute of Technology, Newark, NJ 07102, USA.
LA  - eng
PT  - Journal Article
DEP - 20210710
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC8309173
OTO - NOTNLM
OT  - breakage kinetics
OT  - microhydrodynamic model
OT  - poorly water-soluble drugs
OT  - process modeling
OT  - statistical model
OT  - subset selection
OT  - wet stirred media milling
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/11 06:00
MHDA- 2021/08/11 06:01
PMCR- 2021/07/10
CRDT- 2021/08/10 01:02
PHST- 2021/05/31 00:00 [received]
PHST- 2021/07/07 00:00 [revised]
PHST- 2021/07/07 00:00 [accepted]
PHST- 2021/08/10 01:02 [entrez]
PHST- 2021/08/11 06:00 [pubmed]
PHST- 2021/08/11 06:01 [medline]
PHST- 2021/07/10 00:00 [pmc-release]
AID - pharmaceutics13071055 [pii]
AID - pharmaceutics-13-01055 [pii]
AID - 10.3390/pharmaceutics13071055 [doi]
PST - epublish
SO  - Pharmaceutics. 2021 Jul 10;13(7):1055. doi: 10.3390/pharmaceutics13071055.