Processes,
Journal Year:
2023,
Volume and Issue:
11(10), P. 2919 - 2919
Published: Oct. 5, 2023
Drug
delivery
systems
(DDS)
are
formulations
or
devices
that
enable
the
introduction
of
a
therapeutic
into
body
and
its
to
target
site,
potentially
enhancing
efficacy
safety.
Advances
in
formulation
approaches
related
enhancement
solubility,
permeability
thus
bioavailability
drugs
have
already
been
successfully
implemented
by
pharmaceutical
industry.
This
review
highlights
importance
formulations/DDS
clinical
development
lifecycle
drug
products.
Examples
from
authorised
products
used
showcase
how
appropriate
could
deliver
site
action
(e.g.,
pulmonary
nasal
delivery)
enhance
patient
adherence
medication
long-acting
injectables,
3D-printed
tablets).
Moreover,
examples
provided
highlight
can
improve
safety
liposomes,
abuse-deterrent
opioid
formulations)
albumin-based
nanoparticles,
permeation
enhancers
for
oral
peptides).
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(31), P. 21401 - 21416
Published: June 26, 2024
Long-acting
drug
delivery
systems
are
promising
platforms
to
improve
patient
adherence
medication
by
delivering
drugs
over
sustained
periods
and
removing
the
need
for
patients
comply
with
oral
regimens.
This
research
paper
provides
a
proof-of-concept
development
of
new
optimized
in
situ
forming
injectable
depot
based
on
tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine
peptoid-D-peptide
formulation
((NPhe)4GGGGk(AZT)y(p)-OH).
The
chemical
versatility
peptoid-peptide
motif
allows
low-molecular-weight
be
precisely
covalently
conjugated.
After
subcutaneous
injection,
hydrogel
forms
from
solubilized
peptoid-peptide-drug
response
phosphatase
enzymes
present
within
skin
space.
system
is
able
deliver
clinically
relevant
concentrations
model
drug,
antiretroviral
zidovudine
(AZT),
35
days
Sprague–Dawley
rats.
Oscillatory
rheology
demonstrated
that
formation
began
∼30
s,
an
important
characteristic
reducing
initial
bursts.
Gel
continued
up
∼90
min.
Small-angle
neutron
scattering
data
reveal
narrow-radius
fibers
(∼0.78–1.8
nm)
closely
fit
via
flexible
cylinder
elliptical
model.
inclusion
non-native
peptoid
monomers
D-variant
amino
acids
confers
protease
resistance,
enabling
enhanced
biostability
vitro.
Drug
release
proceeds
hydrolysis
ester
linkage
under
physiological
conditions,
releasing
unmodified
form
further
burst.
Subcutaneous
administration
(NPhe)4GGGGk(AZT)y(p)-OH
rats
resulted
blood
plasma
90%
maximal
inhibitory
concentration
(IC90)
range
(30–130
ng
mL–1)
days.
Molecular Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
21(9), P. 4238 - 4258
Published: Aug. 19, 2024
The
increasing
focus
on
patient
centricity
in
the
pharmaceutical
industry
over
past
decade
and
changing
healthcare
landscape,
driven
by
factors
such
as
increased
access
to
information,
social
media,
evolving
demands,
has
necessitated
a
shift
toward
greater
connectivity
understanding
of
patients'
unique
treatment
needs.
One
technology
that
supported
these
efforts
is
long
acting
injectables
(LAIs),
which
lower
administration
frequency
for
patient's
provided
convenience,
better
compliance,
hence
therapeutical
patients.
Furthermore,
patients
with
conditions
like
human
immunodeficiency
virus
schizophrenia
have
positively
expressed
desire
less
frequent
dosing,
obtained
through
LAI
formulations.
In
this
work,
comprehensive
analysis
marketed
LAIs
across
therapeutic
classes
technologies
conducted.
demonstrated
an
number
new
being
brought
market,
recently
most
aqueous
suspensions
one
solution,
but
many
other
platforms
were
applied
well,
particular,
polymeric
microspheres
situ
forming
gels.
insight
into
physicochemical
properties
compounds
had
per
class
well
knowledge
excipients
typically
used
within
individual
formulation
technology.
principle
behind
was
discussed
respect
release
mechanism,
manufacturing
approaches,
possibility
defining
predictive
vitro
methods
obtain
vivo
correlations
industrial
angle.
gaps
field
are
still
numerous,
including
systematic
investigations
get
potential
innovations,
also
development
polymers
could
facilitate
additional
compounds.
biggest
important
gaps,
however,
seem
be
dissolution
utilizing
pharmacopoeia
described
equipment
enable
their
use
product
later
cycle
quality-based
purposes.
International Journal of Pharmaceutics,
Journal Year:
2023,
Volume and Issue:
646, P. 123455 - 123455
Published: Sept. 28, 2023
Aqueous
nano-
and
microsuspensions
containing
poorly
water-soluble,
crystalline
drug
particles
have
in
the
recent
years
sparked
an
interest
for
preparation
of
long-acting
injectables
(LAIs),
which
increase
patient
compliance
patients
treated
long-term
or
chronic
conditions.
Nano-
are
often
prepared
by
top-down
methods,
such
as
wet
bead
milling,
with
addition
stabilizers
dispersion
media,
surfactants,
influence
particle
sizes
physical
stability
suspension.
To
improve
efficacy
formulation
screening
microsuspensions,
dual
centrifugation
was
utilized
this
study
whereby
40
samples
could
be
manufactured
simultaneously
to
support
definition.
Hence,
type
concentration
stabilizer
well
size
milling
speed
investigated
throughout
presented
study,
but
also
ability
method
produce
consistent
data
investigated.
The
obtained
results
demonstrated
that
profile
after
very
from
run
so
observed
data,
i.e.,
running
n
=
1
experiment
per
combination
clearly
justified
a
predictable
approach
screening.
showed
stabilizer,
its
highly
influenced
suspensions
both
two
model
compounds,
cinnarizine
indomethacin,
where
biggest
within
first
week.
For
short-term
studies,
polysorbate
20
found
suitable
cinnarizine,
whereas
sodium
dodecyl
sulphate
more
indomethacin
immediately
even
1%
(w/v)
solution,
not
sufficient
due
insufficient
concentration.
Smaller
achieved
smallest
at
highest
1500
rpm
without
disrupting
crystal
structure
active
pharmaceutical
ingredient
(API),
confirmed
X-ray
Powder
Diffraction.
International Journal of Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
654, P. 123977 - 123977
Published: March 6, 2024
Bottom-up
production
of
active
pharmaceutical
ingredient
(API)
crystal
suspensions
offers
advantages
in
surface
property
control
and
operational
ease
over
top-down
methods.
However,
downstream
separation
concentration
pose
challenges.
This
proof-of-concept
study
explores
membrane
diafiltration
as
a
comprehensive
solution
for
processing
API
produced
via
anti-solvent
crystallization.
It
involves
switching
the
residual
solvent
(N-methyl-2-pyrrolidone,
NMP)
with
water,
adjusting
excipient
(d-α-Tocopherol
polyethylene
glycol
1000
succinate,
TPGS)
quantity,
enhancing
loading
(solid
concentration)
itraconazole
suspensions.
NMP
was
decreased
from
9
wt%
to
below
0.05
(in
compliance
European
Medicine
Agency
guidelines),
while
TPGS
0.475
0.07
wt%.
reduced
TPGS-to-itraconazole
ratio
1:2
less
than
1:50
raised
1
35.6
Importantly,
these
changes
did
not
adversely
affect
stability
suspension.
presents
one-step
address
challenges
bottom-up
suspension
production.
These
findings
contribute
optimizing
manufacturing
processes
hold
promise
advancing
development
long-acting
techniques
at
commercial
scale.
International Journal of Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
665, P. 124726 - 124726
Published: Sept. 16, 2024
Aqueous
suspensions
of
poorly
soluble,
crystalline
drug
particles
in
the
sub-micron
range
hold
ability
to
regulate
release
for
a
defined
period
time
after
e.g.,
intramuscular,
or
subcutaneous
administration,
working
as
an
eminent
formulation
strategy
preparation
long-acting
injectables.
are
typically
prepared
by
top-down
approaches,
wet
bead
media
milling
high-pressure
homogenization,
containing
active
pharmaceutical
compound
and
surfactants
and/or
polymers
stabilization
purposes.
Currently,
screening
proper
stabilizers
adequate
stabilizer
concentration
during
investigations
is
based
on
trial-and-error
approach
with
variations
combinations,
concentrations,
ratios.
To
obtain
more
efficient
methodology
screening,
present
study
investigated
correlation
between
surface
activity
two
different
surfactants,
i.e.,
poloxamer
188
polysorbate
20,
drop
profile
tensiometry
Langmuir
trough
monolayer,
obtained
sizes
cinnarizine
tool
predict
optimal
surfactant
prepare
physical
stable
nano-
microsuspensions.
The
results
demonstrated
that
molecular
area
determined
per
molecule
measured
combined
specific
could
be
used
suitable
upon
short-term
stress
stability
data.
further
showed
higher
concentrations
were
necessary
stabilize
when
compared
needed
20.
In
addition,
it
was
observed
there
need
slightly
milled
smallest
size
0.5
mm
instead
larger
(0.8
1.0
mm),
which
not
accounted
differences
area.
