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An update on electrostatic powder coating for pharmaceuticals

Authors:
  • The University of Western Ontario / Western University

Abstract and Figures

Derived from dry powder coating of metals, electrostatic powder coating for pharmaceuticals is a technology for coating drug solid dosage forms. In this technology, coating powders, containing coating polymers, pigments, and other excipients, are directly sprayed onto the surface of the solid dosage forms through an electrostatic gun without using any organic solvent or water. The deposited coating powders are further cured to form a coating film. Electrostatic powder coating technology has many advantages compared to other pharmaceutical coating methods. It can eliminate the limitations caused by the organic solvent in solvent coating such as environmental issues and health problems. And electrostatic powder coating technology also surpasses aqueous coating due to its shorter processing time and less energy consumption, leading to a lower overall cost. Furthermore, the utilization of electrical attraction can promote the movement of coating powders towards the substrate, leading to an enhanced coating powder adhesion and coating efficiency, which make it more promising compared to other dry coating technologies. The objective of this review is to summarize the coating principles, apparatus, and formulations of different electrostatic powder coating technologies, giving their advantages and limitations and also analyzing the future application in the industry for each technology.
Content may be subject to copyright.
Please
cite
this
article
in
press
as:
Yang,
Q.,
et
al.
An
update
on
electrostatic
powder
coating
for
pharmaceuticals.
Particuology
(2016),
http://dx.doi.org/10.1016/j.partic.2016.10.001
ARTICLE IN PRESS
G Model
PARTIC-959;
No.
of
Pages
7
Particuology
xxx
(2016)
xxx–xxx
Contents
lists
available
at
ScienceDirect
Particuology
j
our
na
l
ho
me
page:
www.elsevier.com/locate/partic
Review
An
update
on
electrostatic
powder
coating
for
pharmaceuticals
Qingliang
Yanga,c,
Yingliang
Maa,b,
Jesse
Zhua,c,,
Kwok
Chowb,
Kaiqi
Shic
aParticle
Technology
Research
Centre,
Department
of
Chemical
and
Biochemical
Engineering,
University
of
Western
Ontario,
London,
Ontario
N6A
5B9,
Canada
bPowder
Pharma
Coatings,
Mississauga,
Ontario
L5R
2Y9,
Canada
cNingbo
Weston
Powder
Pharma
Coatings
Co.
Ltd.,
Ningbo,
Zhejiang
315
042,
China
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
21
June
2016
Received
in
revised
form
2
October
2016
Accepted
12
October
2016
Available
online
xxx
Keywords:
Electrostatic
powder
coating
Solid
dosage
forms
Plasticizers
Powder
adhesion
Film
formation
Curing
a
b
s
t
r
a
c
t
Derived
from
dry
powder
coating
of
metals,
electrostatic
powder
coating
for
pharmaceuticals
is
a
technol-
ogy
for
coating
drug
solid
dosage
forms.
In
this
technology,
coating
powders,
containing
coating
polymers,
pigments,
and
other
excipients,
are
directly
sprayed
onto
the
surface
of
the
solid
dosage
forms
through
an
electrostatic
gun
without
using
any
organic
solvent
or
water.
The
deposited
coating
powders
are
further
cured
to
form
a
coating
film.
Electrostatic
powder
coating
technology
has
many
advantages
compared
to
other
pharmaceutical
coating
methods.
It
can
eliminate
the
limitations
caused
by
the
organic
solvent
in
solvent
coating
such
as
environmental
issues
and
health
problems.
And
electrostatic
powder
coating
technology
also
surpasses
aqueous
coating
due
to
its
shorter
processing
time
and
less
energy
consump-
tion,
leading
to
a
lower
overall
cost.
Furthermore,
the
utilization
of
electrical
attraction
can
promote
the
movement
of
coating
powders
towards
the
substrate,
leading
to
an
enhanced
coating
powder
adhesion
and
coating
efficiency,
which
make
it
more
promising
compared
to
other
dry
coating
technologies.
The
objective
of
this
review
is
to
summarize
the
coating
principles,
apparatus,
and
formulations
of
different
electrostatic
powder
coating
technologies,
giving
their
advantages
and
limitations
and
also
analyzing
the
future
application
in
the
industry
for
each
technology.
©
2016
Chinese
Society
of
Particuology
and
Institute
of
Process
Engineering,
Chinese
Academy
of
Sciences.
Published
by
Elsevier
B.V.
All
rights
reserved.
Contents
Introduction
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Electrostatic
powder
coating
for
pharmaceuticals
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Principles
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Earlier
attempts
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The
“ExsicCoat”
technology
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Film
formation
mechanism
and
its
influencing
factors
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Conclusions
and
future
perspective
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Acknowledgements
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References
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Introduction
In
the
pharmaceutical
industry,
solid
dosage
forms,
including
tablets
and
pellets,
are
always
coated
to
enhance
drug’s
physi-
Corresponding
author
at:
Particle
Technology
Research
Centre,
Department
of
Chemical
and
Biochemical
Engineering,
University
of
Western
Ontario,
London,
Ontario
N6A
5B9,
Canada.
E-mail
address:
jzhu@uwo.ca
(J.
Zhu).
cal
and
chemical
properties,
to
achieve
odor/taste
masking
and
also
to
alter
drug
release
profiles
including
immediate
release,
sustained/controlled
release,
and
delayed
release
(Siepmann,
Bodmeier,
&
McGinity,
2013).
The
aim
of
immediate
release
coating
is
to
obtain
odor/taste
masking
and
protect
the
drug
from
mois-
ture
and/or
light.
Sustained/controlled
release
coating
allows
drug
releasing
slowly
within
a
desirable
time
period,
which
can
decrease
dosing
frequency
and
enhance
patient
adherence,
reducing
or
elim-
inating
side
effect
associated
with
high
peak
plasma
concentration
(Liu
et
al.,
2012).
Enteric
coating
could
achieve
drug
delayed
release,
http://dx.doi.org/10.1016/j.partic.2016.10.001
1674-2001/©
2016
Chinese
Society
of
Particuology
and
Institute
of
Process
Engineering,
Chinese
Academy
of
Sciences.
Published
by
Elsevier
B.V.
All
rights
reserved.
Please
cite
this
article
in
press
as:
Yang,
Q.,
et
al.
An
update
on
electrostatic
powder
coating
for
pharmaceuticals.
Particuology
(2016),
http://dx.doi.org/10.1016/j.partic.2016.10.001
ARTICLE IN PRESS
G Model
PARTIC-959;
No.
of
Pages
7
2
Q.
Yang
et
al.
/
Particuology
xxx
(2016)
xxx–xxx
protecting
the
drug
from
gastric
acid
and
enzymes
for
the
first
two
hours
at
low
pH
(typically
seen
in
stomach)
and
releasing
drug
immediately
after
exposed
to
the
higher
pH
of
the
small
intestines
(Liu
et
al.,
2012).
Nowadays
liquid
coating
methods,
including
solvent
coating
and
aqueous
coating,
are
widely
used
in
the
pharmaceutical
indus-
try
to
obtain
the
coating
film
for
those
solid
dosage
forms.
In
the
solvent
coating
process,
coating
polymers
and
other
excipients
are
dissolved
into
an
organic
solvent
to
form
a
coating
solution,
which
is
sprayed
onto
the
surface
of
the
solid
dosage
forms
to
form
a
coating
film
by
evaporating
the
organic
solvent
(Liu
et
al.,
2012).
The
film
formation
from
organic
solvent
coating
occurs
by
evapo-
rating
organic
solvent
during
the
drying
process
and
bringing
into
contact
of
individual
polymer
molecules
(Pearnchob
&
Bodmeier,
2003;
Wesseling
&
Bodmeier,
1999).
As
a
result,
the
film
formation
from
solvent
coating
is
quite
uniform.
However,
it
can
cause
many
problems
due
to
the
presence
of
organic
solvent
such
as
toxicity
and
environmental
concerns.
Besides,
the
concentration
of
the
coating
solution
cannot
be
very
high
owing
to
the
viscosity
limit,
leading
to
a
long
processing
time
to
achieve
high
coating
thickness.
As
a
result
of
toxicity
and
environmental
concerns,
aqueous
coating
started
to
dominate
in
1990s
and
remains
the
preferred
approach
in
the
present
pharmaceutical
industry.
For
water
soluble
polymers,
the
coating
process
and
film
formation
mechanism
are
the
same
as
organic
solvent
coating.
For
water-insoluble
polymers,
the
coating
process
and
film
formation
are
different.
Coating
poly-
mers
and
additives
are
firstly
ground
into
fine
powders.
After
mixed
together,
those
fine
powders
are
dispersed
into
water
to
form
a
coating
suspension.
This
suspension
is
then
sprayed
onto
the
sur-
face
of
the
solid
dosage
forms,
followed
by
an
evaporating
by
a
flow
of
hot
air
and
curing
step
to
allow
the
polymer
particles
coalesc-
ing
into
a
homogeneous
film.
Plasticizers
are
often
added
into
the
coating
formulation
to
reduce
the
glass
transition
temperature
(Tg)
of
the
coating
polymer
(Pearnchob
&
Bodmeier,
2003).
Although
there
is
no
toxicity
and
environmental
related
problems
for
aque-
ous
coating,
it
still
possesses
many
limitations.
First,
water
is
more
difficult
to
be
evaporated
compared
to
organic
solvent,
leading
to
a
much
longer
processing
time
and
much
higher
energy
consump-
tion.
Also
hot
air
and
its
handling
are
necessary
to
evaporate
water
in
the
coating
process,
which
could
further
increase
the
overall
cost.
In
addition,
aqueous
coating
is
not
appropriate
for
the
moisture
sensitive
drugs.
In
order
to
overcome
the
disadvantages
caused
by
organic
solvent
and
water
in
the
coating
process,
dry
coating
technolo-
gies
have
been
developed
and
reported
(Bose
&
Bogner,
2007;
Luo,
Zhu,
Ma,
&
Zhang,
2008;
Sauer,
Cerea,
DiNunzio,
&
McGinity,
2013).
These
technologies
include
compression
coating
(Rujivipat
&
Bodmeier,
2012),
photocuring
coating
(Kutal,
Grutsch,
&
Yang,
1991),
supercritical
coating
(Ni,
Xu,
Xu,
Wang,
&
Yin,
2011;
Yue
et
al.,
2004),
hot-melt
coating
(Achanta,
Adusumilli,
James,
&
Rhodes,
1997;
Dreu,
Lustrik,
Perpar,
Zun,
&
Srcic,
2012;
Hampel,
Buck,
Peglow,
&
Tsotsas,
2013),
and
dry
powder
coating
(Cerea,
Zheng,
Young,
&
McGinity,
2004;
Kablitz,
Harder,
&
Urbanetz,
2006;
Kablitz,
Kappl,
&
Urbanetz,
2008;
Kablitz
&
Urbanetz,
2007;
Obara,
Maruyama,
Nishiyama,
&
Kokubo,
1999;
Pearnchob
&
Bodmeier,
2003).
Although
those
dry
coating
technologies
could
minimize
some
limitations
of
liquid
coating
caused
by
organic
solvent
and
water,
the
requirements
for
specific
coating
conditions
and
suitable
coating
materials
make
it
hard
to
apply
them
in
the
pharmaceutical
industry.
In
the
compression
coating
process
(Rujivipat
&
Bodmeier,
2012),
mixture
of
core
formulation
is
first
compressed
into
an
inner
layer
core
and
then
coating
materials
is
compressed
around
the
core
to
form
an
outer
layer
film.
The
main
problem
for
the
com-
pression
coating
is
that
the
coating
thickness
is
not
uniform
owing
to
the
reproducibility
issues
of
placement
of
the
core
in
the
center.
Photocuring
coating
(Kutal
et
al.,
1991)
involves
a
free-radical
poly-
merization
reaction
of
photocurable
materials
to
form
a
crosslinked
network.
This
coating
process
can
be
performed
rapidly
at
room
temperature
or
below
and
it
is
the
only
reported
chemical
approach
so
far
to
form
the
coating
film.
But
this
coating
method
is
not
suit-
able
for
the
photosensitive
drugs.
Also
its
use
is
limited
by
the
specific
photocurable
materials
and
coating
equipment.
Supercrit-
ical
fluid
coating
(Ni
et
al.,
2011;
Tsutsumi,
Nakamoto,
Mineo,
&
Yoshida,
1995;
Yue
et
al.,
2004)
can
be
used
to
coat
small
parti-
cles
uniformly
by
encapsulating
each
core
with
coating
materials
under
a
supercritical
condition.
However,
the
application
of
this
coating
method
is
limited
due
to
the
poor
solubility
of
most
coat-
ing
materials
in
supercritical
fluid
and
also
the
requirement
of
the
core
to
be
insoluble.
For
the
hot-melt
coating
(Achanta
et
al.,
1997;
Chen,
Shi,
Liu,
&
Tang,
2010;
Jannin
&
Cuppok,
2013;
Sinchaipanid,
Junyaprasert,
&
Mitrevej,
2004),
coating
materials
is
applied
in
their
molten
state.
The
coating
process
includes
several
steps.
First,
the
coating
equipment
is
warmed,
and
then
substrate
is
preheated.
Coating
materials
is
melted
and
sprayed
onto
the
surface
of
the
substrate,
followed
by
the
cooling
step
to
allow
the
film
forma-
tion.
This
coating
method
is
only
suitable
for
the
drug
with
stable
properties
at
or
below
the
congealing
point
of
the
coating
materials.
While
for
the
dry
powder
coating
technologies
(Kablitz
et
al.,
2006,
2008;
Kablitz
&
Urbanetz,
2007;
Pearnchob
&
Bodmeier,
2003),
liquid
plasticizers
have
to
be
sprayed
onto
the
surface
of
the
solid
dosage
forms
to
reduce
minimum
film
formation
temperature
and
surplus
plasticizer
can
possibly
lead
to
very
soft
or
sticky
film,
so
that
careful
balance
needs
to
be
reached
between
the
plasticizer
concentration
for
a
sufficient
coat
thickness
and
that
for
a
flexible
and
dry
coat.
And
also
the
coating
powder
feeding
cannot
be
well
controlled
and
it
is
difficult
to
get
a
smooth
and
thickness-uniform
coating
film.
Compared
to
those
dry
coating
technologies,
electrostatic
pow-
der
coating
has
gained
more
attention
owing
to
its
distinct
advantages,
such
as
short
coating
process,
highly
valued
for
energy
savings,
and
significantly
reduction
of
overall
operation
cost.
And
most
importantly,
electrostatic
powder
coating
not
only
could
enhance
the
coating
powder
adhesion
so
as
to
significantly
increase
the
coating
efficiency,
but
also
could
control
the
coating
powder
feeding
and
achieve
more
uniform
coating
film
both
on
coating
thickness
and
surface
morphology.
Recently
many
electrostatic
powder
coating
technologies
have
been
developed
for
pharma-
ceutical
dosage
forms,
including
coating
apparatus
and
coating
formulations.
Some
of
these
technologies
are
very
close
to
be
applied
in
the
industry
due
to
those
mentioned
advantages.
A
sum-
mary
of
such
works
can
bring
lots
of
benefits
to
this
area.
The
aim
of
this
review
is
to
give
an
introduction
and
discussion
on
the
basic
principles,
coating
equipment,
coating
process
and
future
development
of
electrostatic
powder
coating
technologies
for
pharmaceuticals.
Electrostatic
powder
coating
for
pharmaceuticals
Principles
The
concept
of
electrostatic
powder
coating
came
out
in
the
1950s
in
USA,
and
now
it
is
widely
used
in
the
industry
coatings,
furniture
and
construction
industries.
In
the
electrostatic
powder
coating
process
(Fig.
1),
dry
powders
are
charged
by
an
electrostatic
spray
gun
and
then
move
and
adhere
to
the
grounded
substrate
sur-
face
without
using
any
solvent
or
water.
And
then
the
grounded
substrate
with
deposited
coating
powder
is
put
in
an
oven
and
cured
for
a
certain
period
of
time
under
high
temperature
to
allow
film
formation.
Please
cite
this
article
in
press
as:
Yang,
Q.,
et
al.
An
update
on
electrostatic
powder
coating
for
pharmaceuticals.
Particuology
(2016),
http://dx.doi.org/10.1016/j.partic.2016.10.001
ARTICLE IN PRESS
G Model
PARTIC-959;
No.
of
Pages
7
Q.
Yang
et
al.
/
Particuology
xxx
(2016)
xxx–xxx
3
Fig.
1.
Electrostatic
powder
coating
process.
The
following
steps
are
involved
in
the
coating
powder
deposi-
tion
process.
First,
charged
particles
are
sprayed
onto
the
surface
of
the
grounded
substrate
with
combination
of
mechanical
forces
and
electrostatic
attractions
to
form
a
deposited
layer
of
particles.
And
with
the
deposited
particles
accumulating
on
the
substrate,
an
electrical
charge
begin
to
build
up,
which
starts
to
hinder
the
pow-
der’s
further
layering
so
as
to
limit
the
thickness
of
each
layer
(Luo
et
al.,
2008).
In
order
to
successfully
carry
out
the
electrostatic
spraying
pro-
cess,
a
powder
charging
unit
is
needed.
Corona
charging
gun
is
widely
used
to
spray
the
coating
powders.
This
process
involves
the
electrical
breakdown
and
ionization
of
air
by
imposing
a
high
voltage
on
a
sharp
pointed
needle-like
electrode.
As
a
result,
there
will
be
an
electric
field
between
the
gun
and
substrate,
which
can
promote
the
coating
powder
adhesion.
When
powder
particles
pass
through
the
gun,
they
will
pick
up
those
negative
ions
on
their
way
to
the
substrate.
The
movement
of
coating
particles
will
be
pro-
moted
by
the
combination
of
mechanical
force
and
electrical
force
from
the
gun
towards
the
substrate
owing
to
the
presence
of
elec-
trical
field
between
the
charging
gun
and
the
grounded
substrate,
leading
to
an
enhanced
coating
powder
adhesion.
Besides
corona
charging
gun,
tribo
charging
gun
is
also
used
in
the
electrostatic
powder
coating
process,
which
is
related
with
the
principle
of
frictional
charging
associated
with
the
dielectric
prop-
erties
of
solid
materials.
Consequently,
there
are
no
free
ions
and
electric
field
between
electrostatic
gun
and
the
substrate.
And
the
movement
of
coating
particles
between
the
gun
and
the
substrate
is
mainly
governed
by
the
mechanical
force,
which
is
produced
by
the
air
blowing
the
powder
towards
the
substrate
from
the
tribo
gun.
In
the
electrostatic
powder
coating
process,
the
substrate
(solid
dosage
forms)
should
also
possess
certain
electrical
conductivity
or
can
be
modified
to
be
conductive
owing
to
the
significant
influence
to
the
coating
powder
deposition
on
solid
dosage
forms.
As
shown
in
Fig.
2,
for
more
conductive
dosage
forms,
the
electrical
charge
of
the
deposited
particles
will
dissipate
quickly
due
to
the
grounding,
so
that
additional
layers
of
coating
powder
can
be
attracted
and
deposited
onto
the
dosage
form
surface.
While
for
the
less
conduc-
tive
dosage
forms,
electrical
charge
of
the
deposited
particles
will
not
dissipate
and
tends
to
build
up
on
the
surface
of
the
dosage
forms,
which
will
impede
further
deposition
of
coating
powder.
1
×
109
m
is
said
to
be
the
maximum
electrical
resistivity
to
allow
the
above
process
to
happen
(Kablitz
&
Urbanetz,
2007).
Unfor-
tunately,
for
most
of
the
pharmaceutical
solid
dosage
forms,
the
electrical
resistivity
is
much
higher
than
1
×
109
m
because
they
contain
the
excipients
with
high
electrical
resistivity.
There
are
several
methods
to
increase
the
electrical
conductivity
of
the
solid
dosage
forms.
First,
the
solid
dosage
forms
can
be
wetted
with
water,
because
the
layers
of
moisture
increase
the
electrical
conductivity
(Bose
&
Bogner,
2007).
In
the
coating
process,
this
can
be
performed
by
exposing
solid
dosage
forms
to
high
humidity
for
a
very
short
time
before
coating.
The
electrical
conductivity
of
solid
dosage
forms
can
be
increased
by
adding
certain
excipients
such
as
dicalcium
phosphate
and
ionic
salts
(1%–3%)
due
to
their
conduc-
tive
properties
(Bose
&
Bogner,
2007).
Surface
modification
with
polar
groups
(e.g.,
quaternary
ammonium
compounds)
could
also
increase
the
electrical
conductivity
of
the
solid
dosage
forms.
These
compounds
can
be
dissolved
in
volatile
solvent
and
then
applied
to
the
surface
where
it
deposits
as
a
thin
film
after
solvent
evapora-
tion,
which
can
absorb
moisture
from
the
atmosphere
and
forms
an
electrically
conductive
layer
(Grosvenor,
1991).
Earlier
attempts
In
recent
years,
a
number
of
efforts
have
been
made
to
design
both
apparatus
and
formulations
of
electrostatic
powder
coating
for
pharmaceuticals.
Those
approaches
involve
design
of
dry
pow-
der
coating
apparatuses
to
increase
coating
efficiency
by
utilizing
electrostatic
attractions,
to
overcome
the
difficulty
of
charging
poorly
electrically
conductive
pharmaceutical
solid
dosages
and
to
increase
the
mobility
of
relatively
small
sized
particles
with
irreg-
ular
shapes.
Fig.
2.
Effect
of
electrical
conductivity
on
powder
deposition.
Please
cite
this
article
in
press
as:
Yang,
Q.,
et
al.
An
update
on
electrostatic
powder
coating
for
pharmaceuticals.
Particuology
(2016),
http://dx.doi.org/10.1016/j.partic.2016.10.001
ARTICLE IN PRESS
G Model
PARTIC-959;
No.
of
Pages
7
4
Q.
Yang
et
al.
/
Particuology
xxx
(2016)
xxx–xxx
Fig.
3.
Perspective
view
of
a
solid
dosage
form
and
a
platen
shield
(Newman
et
al.,
2012).
Hogan,
Stannforth,
Reeves,
and
Page
(2000);
Hogan,
Stannforth,
Reeves,
and
Page
(2006)
designed
an
apparatus
including
electro-
static
spray
guns,
infrared
ray-based
heater,
and
cooling
stations.
This
apparatus
could
make
every
tablet
effectively
grounded
and
can
direct
and
restrict
the
charged
particles
onto
the
surface
of
tablet
core
without
spraying
onto
the
surroundings,
so
that
the
coating
efficiency
can
be
significantly
improved.
Also
the
two
sides
of
a
tablet
can
be
coated
with
different
formulation
or
different
color.
However,
not
all
the
charged
particles
are
deposited
onto
the
tablet
core
because
the
drum
will
also
receive
some,
leading
to
a
waste
of
coating
powder.
And
cleaning
the
apparatus
is
time-
consuming,
which
would
further
increase
the
overall
cost.
Following
the
work
of
Hogan
et
al.,
US
6806017
B2
(Reeves,
Feather,
Nelson,
&
Whiteman,
2004)
introduced
another
electro-
static
coating
apparatus
based
on
a
photoconductive
drum.
The
charged
powder
material
is
first
applied
to
the
photoconductive
drum
and
transferred
to
an
intermediate
belt
and
then
to
the
solid
dosage
forms.
By
doing
this,
it
can
provide
an
arrangement
in
which
the
location
of
the
deposition
of
the
powder
material
can
be
closely
controlled,
enabling
coating
powder
deposition
on
a
solid
dosage
form
in
a
precise
pattern.
Also
it
can
facilitate
the
powder
deposi-
tion
on
a
three
dimensional
surface.
Different
from
those
above
work,
US
20120012055
A1
(Newman,
Impey,
Henley,
Jennings,
&
Hallett,
2012)
reported
another
electrostatic
coating
apparatus
(Fig.
3)
for
pharmaceutical
solid
dosage
forms.
The
apparatus
contains
a
plurality
of
platens,
each
platen
being
arranged
to
hold
a
plurality
of
tablets.
And
each
platen
comprises
an
electrically
conducting
platen
base
and
an
electrically
conducting
platen
shield
located
on
the
platen
base.
Consequently,
the
apparatus
can
control
the
electrostatic
appli-
cation
of
the
powder
more
effectively
by
establishing
an
electric
potential
difference
between
the
platen
base
and
the
platen
shield
during
the
coating
process.
Compared
to
the
conventional
liquid
coating
processes
and
those
non-electrostatic
dry
coating
technologies,
these
earlier
attempts
do
have
some
advantages
such
as
handling
the
dosage
forms
individually
and
gently,
performing
at
ambient
conditions
with
continuous
process,
coating
tablets
with
different
colors.
But
unfortunately,
those
advantages
have
been
compromised
by
the
complicated
coating
process
and
added
cost
of
the
coating
appara-
tus,
offsetting
any
cost
benefit
to
switching
from
liquid
coating
to
powder
coating,
since
those
technologies
require
the
use
of
com-
pletely
different
coating
equipment.
In
addition,
adoption
of
new
Fig.
4.
A
pan
coater
apparatus
for
powder
coating
solid
dosage
forms
(Zhu
et
al.,
2012).
equipment
not
only
incurs
extra
capital
costs,
but
also
introduces
additional
complications
in
operation.
The
“ExsicCoat”
technology
Instead
of
complicated
apparatus
and
coating
process,
pharma-
ceutical
industry
would
prefer
to
accept
a
powder
coating
operated
in
a
simpler
coating
apparatus
that
can
be
easily
adapted
from
the
present
ones,
such
as
pan
coaters,
for
liquid
coating.
Zhu’s
group
in
The
University
of
Western
Ontario
(Zhu,
Luo,
Ma,
&
Zhang,
2012)
designed
and
developed
a
novel
electrostatic
powder
coat-
ing
technology
(Fig.
4),
which
is
called
“ExsicCoat”
technology.
In
the
coating
process,
solid
dosage
forms
(28)
are
loaded
into
the
rotatable,
electrically
grounded
coating
pan
(32)
and
preheated
by
a
heating
source
(38)
for
a
certain
time
period.
And
then
a
spray-
ing
cycle
including
a
film
forming
polymer
powder
spraying
by
an
electrostatic
spray
gun
(36)
and
liquid
plasticizer
spraying
by
an
atomizer
(34)
is
performed
to
allow
coating
powder
deposition.
After
that,
solid
dosage
forms
will
be
remained
in
the
coating
pan
under
a
certain
temperature
to
allow
the
film
formation.
The
“ExsicCoat”
technology
uses
corona
charging
gun
to
spray
the
coating
powders.
By
doing
this,
coating
powder
adhesion
is
significantly
promoted
by
the
combination
of
mechanical
and
elec-
trical
forces.
Also
the
repulsing
force
caused
by
the
negative
charge
between
each
charged
particle
could
benefit
the
coating
powder
distribution,
leading
to
a
more
uniform
coating
film.
Using
liquid
plasticizer
in
the
coating
process
could
bring
many
benefits.
First
of
all,
liquid
plasticizer
could
reduce
the
Tgof
the
coating
materials
so
as
to
achieve
the
film
formation
at
a
rela-
tively
low
temperature.
Also
spraying
a
certain
amount
of
liquid
plasticizer
could
increase
the
electrical
conductivity
of
those
solid
dosage
forms,
leading
to
a
promoted
coating
particle
deposition.
In
addition,
the
spreading
of
liquid
plasticizer
on
the
surface
of
solid
dosage
forms
can
cause
capillary
force
between
deposited
particles,
benefitting
coating
powder
adhesion
and
film
formation.
Compared
to
the
earlier
attempts
of
electrostatic
powder
coat-
ing
technologies,
this
“ExsicCoat”
technology
possesses
many
advantages.
First
of
all,
the
coating
equipment
utilized
in
this
technology
is
simpler
than
other
electrostatic
powder
coating
tech-
nologies.
The
added
benefits
could
be
brought
when
adapting
the
old
liquid
coating
methods
due
to
the
absence
of
big
changes.
Also,
the
combination
of
mechanical
and
electrical
forces
together
with
spraying
of
liquid
plasticizers
could
promote
the
coating
powder
adhesion,
leading
to
an
enhanced
coating
efficiency
and
film
for-
mation.
In
addition
to
the
quantity
of
coating
powder
sprayed,
the
Please
cite
this
article
in
press
as:
Yang,
Q.,
et
al.
An
update
on
electrostatic
powder
coating
for
pharmaceuticals.
Particuology
(2016),
http://dx.doi.org/10.1016/j.partic.2016.10.001
ARTICLE IN PRESS
G Model
PARTIC-959;
No.
of
Pages
7
Q.
Yang
et
al.
/
Particuology
xxx
(2016)
xxx–xxx
5
Fig.
5.
Pictures
of
electrostatic
dry
powder
coated
tablets
and
pellets
using
the
“ExsicCoat”
technology.
((A)
tablets
coated
with
Eudragit®L
100-55;
(B)
pellets
coated
with
Eudragit®RS/RL).
coating
thickness/coating
level
can
also
be
modified
in
a
wide
range
by
adjusting
the
charging
voltage
or
plasticizer
feed
without
caus-
ing
any
other
issues.
Another
benefit
of
the
“ExsicCoat”
technology
is
the
energy
sav-
ings
resulting
from
the
significant
reduction
of
air
handling
and
cleaning
requirements
(capital
and
operating
costs).
In
the
tradi-
tional
liquid
coating
process,
large
amount
of
hot
air
is
necessary
to
evaporate
the
moisture
content
to
form
the
coating
film,
causing
a
significant
energy
and
time
consumption.
And
hot
air
handling
and
equipment
cleaning
would
further
increase
the
overall
cost.
The
“ExsicCoat”
process
could
significantly
bring
down
those
energy
consumption
and
overall
cost
due
to
the
absence
of
solvent
and
water.
While
applying
the
“ExsicCoat”
technology,
several
coating
for-
mulations
have
been
developed
to
form
the
coating
films
for
different
drug
release
profiles.
Qiao
et
al.
(2010)
developed
a
coat-
ing
formulation
containing
Eudragit®RS
and
RL
to
achieve
drug
sustained
release.
Before
coating,
particle
size
of
the
Eudragit®RS
and
RL
as
well
as
the
talc
powder
were
reduced
using
a
grinder
mill.
The
drug
(ibuprofen)
tablets
were
loaded
into
the
coating
pan
and
preheated
first.
And
then
the
coating
powders
were
sprayed
onto
the
surface
of
the
tablets
with
liquid
plasticizer
triethyl
cit-
rate
(TEC),
followed
by
a
curing
step
to
allow
the
film
formation.
According
to
this
study,
drug
release
rate
from
electrostatic
powder
coated
tablets
could
be
adjusted
by
changing
the
coating
level
or
Eudragit®RS/RL
ratio
in
the
coating
formulation.
Similarly
with
the
equipment
and
procedure,
Eudragit®L
100-
55
(Qiao,
Zhang,
Ma,
Zhu,
&
Xiao,
2013)
was
used
as
the
coating
material
to
form
an
enteric
coating
film,
leading
to
a
delayed
drug
release
to
protect
drug
from
gastric
acid
and
enzymes.
The
coating
formulation
also
contained
talc
powder
as
anti-tack
agent.
And
the
stability
tests
showed
that
those
tablets
coated
by
the
“ExsicCoat”
technology
exhibited
an
excellent
stability
under
different
storage
conditions.
Instead
of
coating
pan,
fluidized
bed
is
typically
utilized
to
coat
smaller
solid
dosage
forms
like
pellets
(Dreu
et
al.,
2012;
Hampel
et
al.,
2013;
Larsen,
Sonnergaard,
Bertelsen,
&
Holm,
2003).
In
those
processes,
compressed
hot
air
is
needed
to
fluidize
the
substrates
in
a
cylindrical
column
and
also
to
evaporate
organic
solvent
or
water.
The
hot
air
handling
and
equipment
cleaning
could
add
to
the
over-
all
cost
and
offset
any
benefit
it
could
have.
Yang,
Ma,
and
Zhu
(2015)
applied
the
“ExsicCoat”
technology
to
those
pellets,
signifi-
cantly
reducing
the
overall
cost
caused
by
the
hot
air
handling
and
equipment
cleaning
and
providing
a
promising
method
for
coating
those
smaller
solid
dosage
forms.
Three
different
coating
formula-
tions
based
on
Eudragit®EPO,
Eudragit®RS/RL,
and
Acryl-EZE
were
developed
for
different
drug
release
profiles
including
immediate
release,
sustained
release
and
delayed
release
(Fig.
5).
Film
formation
mechanism
and
its
influencing
factors
The
film
formation
mechanism
for
organic
and
aqueous-based
systems
is
fundamentally
different
(Lecomte,
Siepmann,
Walther,
MacRae,
&
Bodmeier,
2004;
Pearnchob
&
Bodmeier,
2003).
For
the
solvent
coating,
coating
materials,
mixed
with
other
excipients
including
additives
and
pigments,
are
molecularly
dissolved
in
the
appropriate
organic
solvent
to
form
a
coating
solution,
which
is
then
sprayed
onto
the
surface
of
the
solid
dosage
forms.
Film
for-
mation
is
achieved
by
a
loss
of
solvent
and
contact
of
individual
polymer
molecules.
While
in
the
aqueous
coating
process,
a
disper-
sion
of
coating
materials
and
other
excipients
is
sprayed
onto
the
surface
of
the
solid
dosage
forms.
After
the
evaporation
of
water,
particles
of
coating
materials
coalesce
into
a
homogeneous
film.
Film
formation
of
polymer
particles
at
this
dry
state
results
from
deformation
and
viscous
flow
(Kablitz
&
Urbanetz,
2007;
Keddie,
Meredith,
Jones,
&
Donald,
1995).
Solid
or
liquid
plasticizers
are
commonly
added
into
the
formulation
to
decrease
the
glass
tran-
sition
temperature
of
the
coating
polymers.
For
aqueous
coating,
capillary
force
also
plays
a
significant
role
in
coating
particle
coa-
lescence
and
film
formation
(Klar
&
Urbanetz,
2009).
Similar
to
aqueous
coating,
film
formation
of
dry
powder
coating
also
relies
on
the
deformation
and
viscous
flow
of
coating
poly-
mers
(Kablitz
&
Urbanetz,
2007;
Qiao
et
al.,
2013).
As
being
reported
from
previous
study,
softening,
melting,
and
curing
are
the
princi-
pal
stages
in
the
film
formation
during
dry
powder
coating
(Belder,
Rutten,
&
Perera,
2001;
Pfeffer,
Dave,
Wei,
&
Ramlakhan,
2001;
Wulf,
Uhlmann,
Michel,
&
Grundke,
2000).
In
those
reported
dry
powder
coating
processes,
the
substrates
are
often
preheated
above
or
close
to
the
glass
transition
temperature
of
the
coating
poly-
mers
so
that
the
polymer
powders
can
easily
soften
and
adhere
to
the
substrate.
Wulf
et
al.
(2000)
reported
that
melt
surface
tension
plays
a
decisive
role
in
the
film
formation
in
dry
powder
coat-
ings
process.
The
surface
tension
could
be
controlled
and
adjusted
by
modifying
the
coating
formulations,
for
example,
adding
some
leveling
additives
to
the
formulations.
Plasticizers,
including
plas-
ticizer
powders
and
liquid
plasticizers,
are
also
commonly
added
in
the
coating
formulations
to
reduce
the
glass
transition
temperature
(Tg)
of
coating
polymers.
Besides,
spraying
some
liquid
plasticizer
in
dry
powder
coating
process
could
also
enhance
coating
pow-
der
adhesion
(Cerea
et
al.,
2004;
Kablitz
et
al.,
2006;
Kablitz
&
Urbanetz,
2007;
Obara
et
al.,
1999;
Pearnchob
&
Bodmeier,
2003).
Further
studies
(Kablitz
et
al.,
2008;
Klar
&
Urbanetz,
2009)
sug-
gested
that
those
liquid
plasticizers
could
also
promote
capillary
forces
between
the
coating
particles,
leading
to
enhanced
coat-
ing
powder
adhesion
and
increased
coating
efficiency.
Obara
et
al.
(1999)
suggested
that
the
use
of
a
second
liquid
component
in
the
dry
coating
process
might
reduce
the
contact
angle
of
the
liquid
Please
cite
this
article
in
press
as:
Yang,
Q.,
et
al.
An
update
on
electrostatic
powder
coating
for
pharmaceuticals.
Particuology
(2016),
http://dx.doi.org/10.1016/j.partic.2016.10.001
ARTICLE IN PRESS
G Model
PARTIC-959;
No.
of
Pages
7
6
Q.
Yang
et
al.
/
Particuology
xxx
(2016)
xxx–xxx
on
the
polymer
and
promote
capillary
forces
between
the
polymer
particles
and
the
dosage
forms.
The
film
formation
mechanism
in
the
electrostatic
powder
coating
process
is
similar
with
those
above
dry
powder
coating
technologies.
However,
by
applying
electrostatic
spraying
process,
coating
powder
adhesion
will
be
significantly
promoted
by
the
combination
of
electrical
and
mechanical
forces,
hence
coating
efficiency
would
be
increased
dramatically.
Also
coating
powder
adhesion
and
film
formation
could
be
further
enhanced
by
increas-
ing
the
conductivity
of
the
solid
dosage
forms
and
the
coating
powders.
Particle
size
of
the
coating
powders
plays
a
significant
role
in
the
film
formation
in
the
electrostatic
powder
coating
process.
Misev
(1991)
studied
the
relationship
between
charging
efficiency
and
particle
size
and
obtained
the
following
equation:
charging
efficiency =q
mmax
=6
εoE
(o)
dp
(1
+
2εr
1
εr+
1),
where
E
is
the
electric
field
to
which
the
particles
are
subjected,
ε0is
the
permittivity
of
free
space,
εris
the
relative
permittiv-
ity
of
powder
particles,
0is
the
density
of
the
particle,
and
dp
is
the
particle
diameter.
According
to
this
equation,
a
higher
charg-
ing
efficiency
could
be
achieved
by
using
smaller
coating
particles.
Also
smaller
particles
have
larger
specific
surface
area,
benefiting
the
wetting
by
the
liquid
and
softening
and
melting
by
heat,
so
as
to
enhance
the
coating
powder
adhesion
and
film
formation.
Basi-
cally
fine
powder
with
a
diameter
less
than
100
m
is
preferable
for
dry
powder
coating.
While
more
uniform
and
thickness
controlled
coating
film
could
be
achieved
by
applying
ultrafine
powders
(less
than
30
m).
However,
those
ultrafine
powders
are
Group
C
pow-
ders,
which
are
cohesive
with
poor
flowability.
In
order
to
prevent
the
agglomeration
and
effectively
improve
the
flowability
of
the
ultrafine
powders,
flow
agent
with
nano-size
could
be
added
into
the
coating
formulation
(Valverde,
Castellanos,
Ramos,
&
Watson,
2000;
Yang,
Sliva,
Banerjee,
Dave,
&
Pfeffer,
2005;
Zhu
&
Zhang,
2004).
Conclusions
and
future
perspective
Pharmaceutical
dry
coating
technology
has
developed
notice-
ably
over
the
last
decade.
In
particular,
electrostatic
powder
coating
has
gained
tremendous
attention
due
to
its
phenomenal
advan-
tages
such
as
high
coating
efficiency,
uniform
coating
film,
and
low
overall
cost,
and
has
shown
great
promise
to
replace
liquid
coating
in
pharmaceutical
coatings.
The
principles,
coating
appara-
tus
and
coating
formulations
of
electrostatic
powder
coating
were
introduced
in
the
present
review.
Despite
the
weak
conductivity
of
solid
dosage
forms,
the
benefits
of
electrostatic
dry
powder
coat-
ing
have
helped
to
nurture
its
successes
in
such
area.
Some
earlier
attempts
focused
on
apparatus
design
that
was
trying
to
mechan-
ically
manipulate
individual
tablets
for
uniform
coatings,
but
its
complexity
makes
their
use
impractical.
The
“ExsicCoat”
technol-
ogy
developed
by
Zhu’s
group
has
been
able
to
differentiate
itself
from
other
counterparts
owing
to
its
simpler
coating
apparatus
that
can
be
easily
adapted
from
the
present
ones
such
as
pan
coater
systems
for
liquid
coating.
Future
research
on
electrostatic
powder
coating
will
be
carried
on
the
coating
materials
with
high
Tg,
which
is
very
difficult
for
the
dry
coating
process
under
a
relatively
low
temperature.
How-
ever,
those
materials
are
necessary
for
some
special
dosage
forms
and
drug
products.
In
addition,
moisture
sensitive
products
always
bring
troubles
to
the
current
liquid
coating
methods
while
they
are
very
suitable
for
the
electrostatic
powder
coating
technology.
Details
need
to
be
obtained
on
how
to
apply
electrostatic
powder
coating
to
those
moisture
sensitive
products,
which
may
play
a
key
role
in
adopting
the
electrostatic
powder
coating
technology
in
the
pharmaceutical
industry.
Acknowledgements
The
authors
are
grateful
to
the
support
of
NSERC
and
OCE.
Ningbo
Ginseng
Biotech
Co.
Ltd
wants
to
thank
Ningbo
Interna-
tional
Science
and
Technology
Cooperation
Project
(2015D10008).
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