Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Янв. 1, 2024
Abstract
Combining
existing
drug
therapy
is
essential
in
developing
new
therapeutic
agents
disease
prevention
and
treatment.
In
preclinical
investigations,
combined
effect
of
certain
known
drugs
has
been
well
established
treating
extensive
human
diseases.
Attributed
to
synergistic
effects
by
targeting
various
pathways
advantages,
such
as
reduced
administration
dose,
decreased
toxicity,
alleviated
resistance,
combinatorial
treatment
now
being
pursued
delivering
combat
major
clinical
illnesses,
cancer,
atherosclerosis,
pulmonary
hypertension,
myocarditis,
rheumatoid
arthritis,
inflammatory
bowel
disease,
metabolic
disorders
neurodegenerative
Combinatorial
involves
combining
or
co-delivering
two
more
for
a
specific
disease.
Nanoparticle
(NP)-mediated
delivery
systems,
i.e.,
liposomal
NPs,
polymeric
NPs
nanocrystals,
are
great
interest
wide
range
due
targeted
delivery,
extended
release,
higher
stability
avoid
rapid
clearance
at
infected
areas.
This
review
summarizes
targets
diseases,
clinically
approved
combinations
the
development
multifunctional
emphasizes
strategies
based
on
severe
Ultimately,
we
discuss
challenging
NP-codelivery
translation
provide
potential
approaches
address
limitations.
offers
comprehensive
overview
recent
cutting-edge
NP-mediated
combination
Pharmaceutics,
Год журнала:
2023,
Номер
15(4), С. 1161 - 1161
Опубликована: Апрель 6, 2023
Active
pharmaceutical
ingredients
(API)
with
unfavorable
physicochemical
properties
and
stability
present
a
significant
challenge
during
their
processing
into
final
dosage
forms.
Cocrystallization
of
such
APIs
suitable
coformers
is
an
efficient
approach
to
mitigate
the
solubility
concerns.
A
considerable
number
cocrystal-based
products
are
currently
being
marketed
show
upward
trend.
However,
improve
API
by
cocrystallization,
coformer
selection
plays
paramount
role.
Selection
not
only
improves
drug's
but
also
therapeutic
effectiveness
reduces
side
effects.
Numerous
have
been
used
till
date
prepare
pharmaceutically
acceptable
cocrystals.
The
carboxylic
acid-based
coformers,
as
fumaric
acid,
oxalic
succinic
citric
most
commonly
in
products.
Carboxylic
capable
forming
hydrogen
bond
contain
smaller
carbon
chain
APIs.
This
review
summarizes
role
improving
APIs,
deeply
explains
utility
afore-mentioned
cocrystal
formation.
concludes
brief
discussion
on
patentability
regulatory
issues
related
Abstract
Hot-melt
extrusion
(HME)
is
a
globally
recognized,
robust,
effective
technology
that
enhances
the
bioavailability
of
poorly
soluble
active
pharmaceutical
ingredients
and
offers
an
efficient
continuous
manufacturing
process.
The
twin-screw
extruder
(TSE)
extremely
resourceful
customizable
mixer
used
for
compounding
granulation
by
using
different
combinations
conveying
elements,
kneading
elements
(forward
reverse
configuration),
distributive
mixing
elements.
TSE
thus
efficiently
utilized
dry,
wet,
or
melt
not
only
to
manufacture
dosage
forms
such
as
tablets,
capsules,
granule-filled
sachets,
but
also
designing
novel
formulations
dry
powder
inhalers,
drying
units
granules,
nanoextrusion,
3D
printing,
complexation,
amorphous
solid
dispersions.
Over
past
decades,
combined
academic
industry
collaborations
have
driven
innovations
HME
technology,
which
has
resulted
in
substantial
increase
published
articles
patents.
This
article
summarizes
challenges
models
executing
scale-up.
Additionally,
it
covers
benefits
manufacturing,
process
analytical
(PAT)
considerations,
regulatory
requirements.
In
summary,
this
well-designed
review
builds
upon
our
earlier
publication,
probing
deeper
into
potential
extruders
various
new
applications.
Graphical
Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(11), С. 4683 - 4716
Опубликована: Сен. 2, 2024
About
40%
of
approved
drugs
and
nearly
90%
drug
candidates
are
poorly
water-soluble
drugs.
Low
solubility
reduces
the
drugability.
Effectively
improving
bioavailability
is
a
critical
issue
that
needs
to
be
urgently
addressed
in
development
application.
This
review
briefly
introduces
conventional
solubilization
techniques
such
as
solubilizers,
hydrotropes,
cosolvents,
prodrugs,
salt
modification,
micronization,
cyclodextrin
inclusion,
solid
dispersions,
details
crystallization
strategies,
ionic
liquids,
polymer-based,
lipid-based,
inorganic-based
carriers
bioavailability.
Some
most
commonly
used
carrier
materials
for
presented.
Several
using
summarized.
Furthermore,
this
summarizes
mechanism
each
technique,
reviews
latest
research
advances
challenges,
evaluates
potential
clinical
translation.
could
guide
selection
approach,
dosage
form,
administration
route
Moreover,
we
discuss
several
promising
attracting
increasing
attention
worldwide.
Pharmaceutics,
Год журнала:
2025,
Номер
17(1), С. 136 - 136
Опубликована: Янв. 19, 2025
Nanosuspensions
(NS),
with
their
submicron
particle
sizes
and
unique
physicochemical
properties,
provide
a
versatile
solution
for
enhancing
the
administration
of
medications
that
are
not
highly
soluble
in
water
or
lipids.
This
review
highlights
recent
advancements,
future
prospects,
challenges
NS-based
drug
delivery,
particularly
oral,
ocular,
transdermal,
pulmonary,
parenteral
routes.
The
conversion
oral
NS
into
powders,
pellets,
granules,
tablets,
capsules,
incorporation
film
dosage
forms
to
address
stability
concerns
is
thoroughly
reviewed.
article
summarizes
key
stabilizers,
polymers,
surfactants,
excipients
used
formulations,
along
ongoing
clinical
trials
patents.
Furthermore,
comprehensive
analysis
various
methods
preparation
provided.
also
explores
vitro
vivo
characterization
techniques,
as
well
scale-down
technologies
bottom-up
preparation.
Selected
examples
commercial
products
discussed.
Rapid
advances
field
could
resolve
issues
related
permeability-limited
absorption
hepatic
first-pass
metabolism,
offering
promise
based
on
proteins
peptides.
evolution
novel
stabilizers
essential
overcome
current
limitations
stability,
bioavailability,
targeting
ability,
safety
profile,
which
ultimately
accelerates
application
commercialization.
CrystEngComm,
Год журнала:
2022,
Номер
24(11), С. 2002 - 2022
Опубликована: Янв. 1, 2022
Cocrystal
strategies
to
achieve
excellent
physiochemical
performance
under
different
environmental
stress
were
highlighted
here.
The
lattice
energy
and
the
barrier
of
degradation
reactions
are
two
pillars
in
a
stable
cocrystal
construction.
Pharmaceutics,
Год журнала:
2022,
Номер
14(1), С. 94 - 94
Опубликована: Янв. 1, 2022
Hesperetin
(HES)
is
a
key
biological
active
ingredient
in
citrus
peels,
and
one
of
the
natural
flavonoids
that
attract
attention
researchers
due
to
its
numerous
therapeutic
bioactivities
have
been
identified
vitro.
As
bioenhancer,
piperine
(PIP)
can
effectively
improve
absorption
insoluble
drugs
vivo.
In
present
study,
cocrystal
HES
PIP
was
successfully
obtained
through
solution
crystallization.
The
single-crystal
structure
illustrated
comprehensive
characterization
conducted.
formed
by
two
drug
molecules
at
molar
ratio
1:1,
which
contained
O-H-O
hydrogen
bonds
between
carbonyl
ether
oxygen
phenolic
hydroxyl
group
HES.
addition,
solubility
experiment
performed
on
powder
simulated
gastrointestinal
fluid,
result
revealed
improves
dissolution
behavior
compared
with
pure
substance.
Furthermore,
HES's
bioavailability
six
times
higher
than
pristine
drugs.
These
results
may
provide
an
efficient
oral
formulation
for
Molecular Pharmaceutics,
Год журнала:
2023,
Номер
20(5), С. 2293 - 2316
Опубликована: Март 28, 2023
Improving
the
solubility
and
permeability
of
drugs
via
cocrystallization
is
an
important
theme
in
crystal
engineering
with
practical
applications
for
discovery
development
high
bioavailability
medicines.
The
past
decade
has
witnessed
a
surge
publications
on
pharmaceutical
cocrystals/salts
to
improve
Biopharmaceutics
Classification
System
(BCS)
class
IV
drugs.
In
this
review
article,
reader
introduced
fundamentals
drug
mechanisms
then
examples
cocrystals
salts
designed
enhance
diffusion
are
presented,
order
understand
different
structural
factors
that
modulate
flux
transport
across
semipermeable
membrane.
Broadly,
two
main
phenomena
can
be
summarized
from
50
or
so
examples:
(1)
heterosynthons
hydrogen-bonded
drug–coformer
aggregates
survive
long
enough
experimental
media
such
drug,
which
present
concentration
due
supersaturation,
exhibits
higher
(2)
coformer
cocrystal
able
reduce
transepithelial
electrical
resistance
(TEER)
values
lipid
monolayers,
impairs
their
tight
junctions,
facilitates
passage
its
diffusion/permeability.
medicinal
chemistry
literature
recapitulated
idea
these
principles
may
utilized
de
novo
design
coformers
synthesis
improved-performance
cocrystals.
Enhancing
without
changing
molecular
structure
supramolecular
complexes
will
address
poor
challenge
majority
BCS
II
