Microspheres or droplets are increasingly finding various biomedical applications as drug microspheres and multicellular spheroids. Single nozzle-based continuous jetting with the help of acoustic excitation and/or carrier stream is a basic process for monodisperse microsphere fabrication. Precise control of microsphere size and size distribution in single nozzle jetting is still of great manufacturing interest. The objective of this study is to numerically model a glycerol-water microsphere fabrication process during acoustic excitation-based single nozzle continuous jetting. Using a volume of fluid method, this study has investigated the effects of material properties and fabrication conditions such as the acoustic excitation frequency and amplitude and the carrier stream velocity on the size of microspheres fabricated. (1) The microsphere diameter decreases as the glycerol volume percentage increases. (2) The excitation frequency and pressure have a pronounced effect on the microsphere size. The microsphere diameter decreases as the excitation frequency increases, and the microsphere diameter increases with the excitation pressure amplitude. (3) The microsphere size decreases as the carrier stream velocity increases.

1.
Amsden
,
B.
, 1999, “
The Production of Uniformly Sized Polymer Microspheres
,”
Pharm. Res.
0724-8741,
16
, pp.
1140
1143
.
2.
Berkland
,
C.
,
Kim
,
K.
, and
Pack
,
D. W.
, 2001, “
Fabrication of PLG Microspheres With Precisely Controlled and Monodisperse Size Distributions
,”
J. Controlled Release
0168-3659,
73
, pp.
59
74
.
3.
Berkland
,
C.
,
King
,
M.
,
Cox
,
A.
,
Kim
,
K.
, and
Pack
,
D. W.
, 2002, “
Precise Control of PLG Microsphere Size Provides Enhanced Control of Drug Release Rate
,”
J. Controlled Release
0168-3659,
82
, pp.
137
147
.
4.
Berkland
,
C.
,
Pollauf
,
E.
,
Pack
,
D. W.
, and
Kim
,
K.
, 2004, “
Uniform Double-Walled Polymer Microspheres of Controllable Shell Thickness
,”
J. Controlled Release
0168-3659,
96
, pp.
101
111
.
5.
Snider
,
C.
,
Lee
,
S. -Y.
,
Yeo
,
Y.
,
Grégori
,
G. J.
,
Robinson
,
J. P.
, and
Park
,
K.
, 2008, “
Microenvironment-Controlled Encapsulation (MiCE) Process: Effects of PLGA Concentration, Flow Rate, and Collection Method on Microcapsule Size and Morphology
,”
Pharm. Res.
0724-8741,
25
, pp.
5
15
.
6.
Lin
,
R. -Z.
, and
Chang
,
H. -Y.
, 2008, “
Recent Advances in Three-Dimensional Multicellular Spheroid Culture for Biomedical Research
,”
Biotechnol. J.
,
3
, pp.
1172
1184
.
7.
Shah
,
R. K.
,
Shum
,
H. C.
,
Rowat
,
A. C.
,
Lee
,
D.
,
Agresti
,
J. J.
,
Utada
,
A. S.
,
Chu
,
L. -K.
,
Kim
,
J. -W.
,
Fernandez-Nieves
,
A.
,
Martinez
,
C. J.
, and
Weitz
,
D. A.
, 2008, “
Designer Emulsions Using Microfluidics
,”
Mater. Today
1369-7021,
11
, pp.
18
27
.
8.
Pruesse
,
U.
, and
Vorlop
,
K. D.
, 2004, “
The Jetcutter Technology
,”
Fundamentals of Cell Immobilization Biotechnology
,
V.
Nédovic
and
R.
Willaert
, eds.,
Kluwer Academic
,
The Netherlands
, pp.
295
309
.
9.
Lacasse
,
F. -X.
,
Hildgen
,
P.
,
Pérodin
,
J.
,
Escher
,
E.
,
Phillips
,
N. C.
, and
McMullen
,
J. N.
, 1997, “
Improved Activity of a New Angiotensin Receptor Antagonist by an Injectable Spray-Dried Polymer Microsphere Preparation
,”
Pharm. Res.
0724-8741,
14
, pp.
887
891
.
10.
Senuma
,
Y.
,
Lowe
,
C.
,
Zweifel
,
Y.
,
Hilborn
,
J. G.
, and
Marison
,
I.
, 2000, “
Alginate Hydrogel Microspheres and Microcapsules Prepared by Spinning Disk Atomization
,”
Biotechnol. Bioeng.
0006-3592,
67
, pp.
616
622
.
11.
Tabata
,
Y.
, and
Ikada
,
Y.
, 1990, “
Phagocytosis of Polymer Microspheres by Macrophages
,”
Adv. Polym. Sci.
0065-3195,
94
, pp.
107
141
.
12.
Barrow
,
E. L. W.
,
Winchester
,
G. A.
,
Staas
,
J. K.
,
Quenelle
,
D. C.
, and
Barrow
,
W. W.
, 1998, “
Use of Microsphere Technology for Targeted Delivery of Rifampin to Mycobacterium Tuberculosis-Infected Macrophages
,”
Antimicrob. Agents Chemother.
0066-4804,
42
, pp.
2682
2689
.
13.
Berkland
,
C.
,
Kim
,
K.
, and
Pack
,
D. W.
, 2003, “
PLG Microsphere Size Controls Drug Release Rate Through Several Competing Factors
,”
Pharm. Res.
0724-8741,
20
, pp.
1055
1062
.
14.
Sansdrap
,
P.
, and
Moes
,
A. J.
, 1993, “
Influence of Manufacturing Parameters on the Size Characteristics and the Release Profiles of Nifedipine From Poly(DL-Lactide-co-Glycolide) Microspheres
,”
Int. J. Pharm.
0378-5173,
98
, pp.
157
164
.
15.
Berkland
,
C.
,
Kipper
,
M. J.
,
Narasimhan
,
B.
,
Kim
,
K.
, and
Pack
,
D. W.
, 2004, “
Microsphere Size, Precipitation Kinetics, and Drug Distribution Control Drug Release From Biodegradable Polyanhydride Microspheres
,”
J. Controlled Release
0168-3659,
94
, pp.
129
141
.
16.
Rayleigh
,
L.
, 1879, “
On the Capillary Phenomena of Jets
,”
Proc. R. Soc. London
0370-1662,
29
, pp.
71
97
.
17.
Stone
,
H. A.
, 1994, “
Dynamics of Drop Deformation and Breakup in Viscous Fluids
,”
Annu. Rev. Fluid Mech.
0066-4189,
26
, pp.
65
102
.
18.
Eggers
,
J.
, 1997, “
Nonlinear Dynamics and Breakup of Free-Surface Flows
,”
Rev. Mod. Phys.
0034-6861,
69
, pp.
865
930
.
19.
Rayleigh
,
L.
, 1892, “
On the Instability of a Cylinder of Viscous Liquid Under Capillary Force
,”
Philos. Mag.
1478-6435,
34
, pp.
145
154
.
20.
Tomotika
,
S.
, 1935, “
On the Instability of a Cylindrical Thread of a Viscous Liquid Surrounded by Another Viscous Fluid
,”
Proc. R. Soc. London, Ser. A
0950-1207,
150
, pp.
322
337
.
21.
Nayfeh
,
A. H.
, 1970, “
Nonlinear Stability of a Liquid Jet
,”
Phys. Fluids
0031-9171,
13
, pp.
841
847
.
22.
Yuen
,
M. -C.
, 1968, “
Non-Linear Capillary Instability of a Liquid Jet
,”
J. Fluid Mech.
0022-1120,
33
, pp.
151
163
.
23.
Pimbley
,
W. T.
, and
Lee
,
H. C.
, 1977, “
Satellite Droplet Formation in a Liquid Jet
,”
IBM J. Res. Dev.
0018-8646,
21
, pp.
21
30
.
24.
Rallison
,
J. M.
, 1984, “
The Deformation of Small Viscous Drops and Bubbles in Shear Flows
,”
Annu. Rev. Fluid Mech.
0066-4189,
16
, pp.
45
66
.
25.
Lee
,
H. C.
, 1974, “
Drop Formation in a Liquid Jet
,”
IBM J. Res. Dev.
0018-8646,
18
, pp.
364
369
.
26.
Reitz
,
R. D.
, 1987, “
Modeling Atomization Processes in High-Pressure Vaporizing Sprays
,”
Atom. Spray Tech.
,
3
, pp.
309
337
.
27.
Richards
,
J. R.
,
Beris
,
A. N.
, and
Lenhoff
,
A. M.
, 1995, “
Drop Formation in Liquid-liquid Systems Before and After Jetting
,”
Phys. Fluids
0031-9171,
7
, pp.
2617
2630
.
28.
Eggers
,
J.
, and
Dupont
,
T. F.
, 1994, “
Drop Formation in a One-Dimensional Approximation of the Navier–Stokes Equation
,”
J. Fluid Mech.
0022-1120,
262
, pp.
205
221
.
29.
Wilkes
,
E. D.
,
Phillips
,
S. D.
, and
Basaran
,
O. A.
, 1999, “
Computational and Experimental Analysis of Dynamics of Drop Formation
,”
Phys. Fluids
0031-9171,
11
, pp.
3577
3598
.
30.
2006, FLUENT 6.3 User’s Guide, FLUENT Inc., NH, Lebanon.
32.
Lide
,
D. R.
, 2007,
Handbook of Chemistry and Physics
,
88th ed.
,
Taylor &Francis
,
London
.
33.
Rayleigh
,
L.
, 1882, “
On the Equilibrium of Liquid Conducting Masses Charged With Electricity
,”
Philos. Mag.
1478-6435,
14
, pp.
184
186
.
34.
Ambravaneswaran
,
B.
,
Wilkes
,
E. D.
, and
Basaran
,
O. A.
, 2002, “
Drop Formation From a Capillary Tube: Comparison of One-Dimensional and Two-Dimensional Analyses and Occurrence of Satellite Drops
,”
Phys. Fluids
0031-9171,
14
, pp.
2606
2621
.
You do not currently have access to this content.