NANO-EMULSION

(NANO NH TNG)
NI DUNG
A. TNG QUAN
1. Gii thiu
2. Phn loi
3. Nh nano
B. PHNG PHP TO H NH TNG
1. Ultrasonic
2. Microfluidization
3. High-pressure homogenization
C. NG DNG
I. H NH TNG V NH NANO
I.1. H nh tng (emulsion)
I.1.1. Tng quan
H nh tng
II
I
A
B
C D
H phn tn cc cht lng khng ha tan vo nhau.
A. Two immiscible liquids, not yet emulsified.
B. An emulsion of Phase II dispersed in Phase I.
C. The unstable emulsion progressively separates.
D. The surfactant (purple outline around particles)
positions itself on the interfaces between Phase II and Phase I, stabilizing the emulsion
I: Pha lin tc II: Pha phn tn
I.1. H nh tng (emulsion)
I.1.1. Tng quan
Tnh cht v bn ca h nh tng
Oil in water emulsion under microscope Citrus vinaigrette
H nh tng l mt h khng n nh v mt nhit ng.
Qu trnh lc (shaking),khuy trn (stirring),ng ha (hemogenizing)
hoc phun (spray) l cn thit to h nh tng.
I.1. H nh tng (emulsion)
I.1.1. Tng quan
Tnh cht v bn ca h nh tng
http://sparror.cubecinema.com/cube/cola/chemistry/cola1.htm

C 3 dng khng bn (instability) ca h nh tng s tch pha
(Stable emulsion)
(s keo t)
(S kt dnh)
The failure of emulsions.
Emulsion
Particle size
( m)
Appearance
Tyndall effect
Reflected
light
Scattering
light
Unstable
1 - 10
Nano
emulsion
Thermo
dynamic
stability
(Macro)
emulsion
0.1 - 1
Opaque
No No
Bluish
Weak
blue
Weak
red
Microemulsion
0.05 - 0.1
0.005 - 0.02
Blue Red
Translucency
Transparency
Solubilizasion
No
No
Stable
0.02 - 0.05
Stable or
unstable
Classification
Source : Yukagaku, Abe, 41, p117(1992)
Transparency
Stable
I.1. H nh tng (emulsion)
I.1.1. Tng quan
Tnh cht v bn ca h nh tng
Particle sizes and optical properties
The Tyndall effect is light scattering by particles in a colloid or particles, in that the
intensity of the scattered light depends on the fourth power of the frequency,
so blue light is scattered more strongly than red light
I.1. H nh tng (emulsion)
I.1.1. Tng quan
Tnh cht v bn ca h nh tng
S dng DLS (dynamic light scattering) o kch thc phn t phn
tn (droplet sizes) trong h nh tng bn ca h.
Kch thc pha phn tn cng ln + chuyn ng Brown d dn n s kt dnh
hay keo t H khng bn
I.1. H nh tng (emulsion)
I.1.1. Tng quan
Tnh cht v bn ca h nh tng
To bn cho h nh tng: s dng cht n nh (stabilizer)
Cht nh ha (emulsifiers)
Cht b tr b mt (texture modifiers)
Stabilizers
:cc cht hot ng b mt
+ Nng thp, bao quanh b mt phn chia pha.
+ lm gim sc cng b mt h d hnh thnh droplet.
+ To nht (thickening agent) hoc hnh thnh gel (geling agent) ca
pha lin tc.
Lm chm qu trnh chuyn ng Brownian ca cc phn t (droplets)
ca pha phn tn.
-Dn xut t thc vt: agar, pectin, lecithin, carrageenan
- Dn xut t ng vt: gelatin, lanolin, cholesterol
-Cht bn tng hp: methycellulose,
carboxymethylcellulose
- Cht tng hp: carbopols
I.1. H nh tng (emulsion)
I.1.1. Tng quan
Tnh cht v bn ca h nh tng
Ngoi ra, cn c 2 dng to bn h nh tng:
+ Cn bng tnh in (Electrostatic):ph thuc vo nhm phn cc + pH pha lin tc
Cc nhm phn cc y nhau, gim s kt dnh hoc keo t
I.1. H nh tng (emulsion)
I.1.1. Tng quan
Tnh cht v bn ca h nh tng
Ngoi ra, cn c 2 dng to bn h nh tng:
+ S dng polymer (polymeric stabilisation), vd: protein hay gum Arabic
Adsorption of polymers at the O/W surface
=> Gim s kt dnh hay kt t.
Mt s polymer c th ha tan
vo nc lm tng nht
I.1. H nh tng (emulsion)
I.1.2. Cht nh ha (emulsifier)
L mt dng ca cht hot ng b mt (surfactant), c s dng
trong h nh tng nhm gip cho h phn tn tt.


Left:olive oil + water
Right: oil+water+surfactant
Submerged paper clip
afer addition of surfactant
Clip paper floating in oil-in-water
emulsion due to interfacial tension
I.1. H nh tng (emulsion)
I.1.2. Cht nh ha (emulsifier)
Cht hot ng b mt
Cu trc: thng thuc dng amphiphilic
Tnh cht:
+ Bn v mt ha hc trong h
+ Tr v khng phn ng vi cc cht trong h nh tng.
+ Khng c hi, khng mi v khng t.
S chn la cht hot ng b mt:
+ Hydrophilic surfactant O/W emulsion
+ Lipophilic surfactant W/O emulsion
W/O
O/W
+ Kh nng tng thch (Compatibility)
+ To s n nh ca h nh tng nng thp
I.1. H nh tng (emulsion)
I.1.2. Cht nh ha (emulsifier)
Micelles to thnh khi cc cht hot ng b mt t n nng CMC.
Ty pha phn tn l nc hay du m cc cht HBM s a u a
du hay a nc vo trong li ca micelles. Bn trong li ca micelles
l nhng vi ht, micelles nhm gip phn tn cc vi ht ny vo
trong pha lin tc tt hn.
I.1. H nh tng (emulsion)
Micelles
l dng ca h nh tng khi cho cht HBM vo.
Reversve Micelles
S kt t micelle
I.1. H nh tng (emulsion)
I.1.3. Hydrophilic Lipophilic balance (HLB)
I.1. H nh tng (emulsion)
Griffin's method: tnh cho cht HBM nonionic (1954)

HLB = 20 * Mh / M
+ Mh: phn t khi ca u phn cc
+ M: phn t khi ca phn t cht HBM
HLB c gi tr trong khong 0 20
+ High HLB => s dng cht HBM ha tan (phn tn) tt trong H
2
O O/W emulsion.
+ Low HLB => s dng cht HBM ha tan (phn tn) tt trong du W/O emulsion
Gi tr HLB p dng cho cht HBM khng ion. S kt hp nhiu cht HBM s to h
nh tng bn hn l vic s dng 1 cht HBM c cng HLB.

Bancrofts rule
Cht HBM hay cht nh ha c xu hng gip to
pha phn tn l pha m n khng ha tan tt.
VD: + Cho thnh phn 2 pha gm: 60% du + 40% nc. Nu chn cht nh ha ha tan tt
trong nc => pha phn tn l du to h nh Oil in water.
+ Protein ha tan tt trong nc hn trong du => to h nh oil in water
I.1.3. Hydrophilic Lipophilic balance (HLB)
I.1. H nh tng (emulsion)
Vy, s hnh thnh h nh tng dng O/W hay O/W khng ch ph thuc
thnh phn th tch ca pha phn tn v pha lin tc m cn ph thuc vo
cht HBM.
I.2. Phn loi
I. H NH TNG V NH NANO
H nh tng
Thnh phn h nh Kch thc pha phn tn
Oil-in-water
Emulsion
Water-in-oil
Emulsion
Multiple
Emulsion
Pickering
Emulsion
Macroemulsion
Nanoemulsion
Microemulsion
I.2. Phn loi
Gii thiu
Type of emulsion Particle size
Macroemulsion (B) >400nm (0,4 )
Nanoemulsion(A) 100 400nm
Microemulsion(C) <100nm
m
C
Particle size Appearance
>400nm White
100 400 Blue White
< 100 Translucent
< 50nm Transparent
I.2. Phn loi
nh gi h nh tng
Electrical conductivity:
Electrical conductivity of O/W
emulsions is higher than
that of W/O emulsions.
Dilution method:
evaluated from the dispersion
ease at dilution with water.
Dye method:
Evaluated the emulsion type
by dissolving water-soluble
and oil-soluble dyes in the emulsion
I.2. Phn loi
Multiple Emulsion
I.2. Phn loi
Multiple Emulsion
I.2. Phn loi
Pickering Emulsion H nh tng c n nh bi cc ht rn.
Ht rn thng l silica, oxit kim loi, hay ht t st (clay)
I.3. Nh Nano (nanoemulsion miniemulsion finely dispersed emulsion
sub-micronemulsion (SME)- utrafine emulsion)
I. H NH TNG V NH NANO
H nh nano: kch thc phn t phn tn (droplet) t 100-
400nm (20 500nm), c mu hi xanh nht.
Tnh cht h nh nano ph thuc vo thnh phn pha, iu kin
cn bng nhit ng pha v phng php to h nh.
Phng php to h nh nano: s dng phng php ng
ha di p sut cao.
bn: thm cht HBM, nng khong 1-3%.



Ouzo effect
Pha phn tn t n c vai tr l cht HBM, phn tn
di kch thc nano trong pha lin tc to h nh
nano.
Xy ra do nc tng tc vi mt loi ancol mnh lm t cy hi, nh ouzo, pastis,
arak hay raki
I.2. Phn loi
The ouzo effect
after the dilution
of Turkish raki
Ouzo effect
B. PH NG PHP TO H NANO -NH TNG
Nh ha bng
NL thp
(Low Energy)
Nh ha
t ng
Phase
Inversion
Temperature
Phase
Inversion
Composition
Nh ha
bng nng
lng u
vo cao
Ultrasonication
ng ha p
sut cao
Microfluidization
B. PH NG PHP TO H NANO -NH TNG
1.1. Tc ng ca sng siu m trong dung dch lng
Sng siu m l sng dc, c chiu di sng khong 10 -10
-3
cm
khng nng lng tng tc vo lin kt ha hc

Khi chiu x siu m trong mi trng lng li sinh ra nng
lng ln do hin tng vt l cavitation (hin tng kh thc):
S co
gin
cht
lng
Cht lng
+
ultrasonic
To l
hng
(bt)
Negative
perssure
vt
bn ko
ca cht
lng
V
bt
Kch
thc
bt tng
dn
Hot
spot
B. PH NG PHP TO H NANO -NH TNG
Hot-spot
S tng dn kch thc dn n s b bt trong lng cht
lng di tc dng ca ultrasonic
Hot-spot c t
o
~ 5000
o
C, p ~1000atm, thi gian sng ngn
hn 1microsecond, tc gia nhit-lm lnh >10t
o
C/giy
(do trong mi trng xung quanh l lng lnh nn s gia nhit
nhanh chng c dp tt, nn n tn ti trong thi gian
ngn.)
B. PH NG PHP TO H NANO -NH TNG
1.2. Nh tng ha bng sng siu m
Mt dng my to ultrasonic
Cavitation l hin tng ch o trong qu trnh to nano nh
tng bng ultrasonic nh vo hot-spot. S ph v cc bt to ra
nhng sng cc mnh lan ta trong dung dch ph v cc phn
tn lng thnh cc vi ht hnh thnh nn h nh tng.
B. PH NG PHP TO H NANO -NH TNG
1.2. Nh tng ha bng sng siu m
C ch hnh thnh h nh tng bng siu m gm hai bc:

Bc u tin: sng siu m tc ng ca vo b mt phn
chia pha gia pha lin tc v pha phn tn, gip phn tn cc
git vo pha lin tc.

Bc th hai: dc tc ng ca hin tng cavitation to
nn cc hiu ng mnh m ca sng lm ph v cc git phn
tn lng thnh nhng vi git c kch thc rt nh. Hnh thnh
nn h nano nh tng
B. PH NG PHP TO H NANO -NH TNG
1.2. Nh tng ha bng sng siu m
B. PH NG PHP TO H NANO -NH TNG
T hn hai thp k qua, cc nh nghin cu v sn xut
dc phm s dng h thng x l cao Microfluidizer

to cc dung dch phn tn ng nht vi kch thc ht phn
tn c nano.

Ban u, hai dung dch (thng l pha nc v pha du
mt l pha phn tn v mt l pha lin tc) c th c trn
vi nhau v c x l to ra dung dch nh tng th (tc
kch thc cc ht phn tn ln). Sau nh tng th s
c a vo h thng x l cao Microfluidizer tip tc x
l nhm thu c h nano-nh tng ng nht v n nh
B. PH NG PHP TO H NANO -NH TNG
Qu trnh x l trong Microfluidizer c m t theo s
sau:
B. PH NG PHP TO H NANO -NH TNG
Bm p sut cao
(1.500 - 40.000psi)
y sp vo bung
tng tc
(v>400m/s)
Sp va chm trong
cc vi knh cc
nh ph v
cc ht phn tn
thnh vi ht
Sp c lm lnh
h nano-nh
tng
B. PH NG PHP TO H NANO -NH TNG
ng ha p sut cao thc hin bng cch
cho dng phn tn i qua mt knh hoc l rt hp
di tc ng ca p sut rt cao nhm ph v cc
ht c kch thc ln thnh vi ht.

H thng ng ha p cao gm ba khu vc
chnh:
Bm p sut cao
Khoang ng ha
Khoang trao i nhit
B. PH NG PHP TO H NANO -NH TNG
Cu to chnh ca khoang ng ha:
B. PH NG PHP TO H NANO -NH TNG
Cu to chnh ca khoang ng ha:
(a)
(b)
(c)
(a) Van (valve)
(b) Vng m (impact ring)
(c) Mt m c nh (seat)
Mt m
vt cnh
Mt m
cong
B. PH NG PHP TO H NANO -NH TNG
ng ha p sut cao c thc hin theo cc bc nh sau:
Bm p sut cao
y dng sp vi
tc c cc ln
n khoang ng
ha.
- Lc xoy dng chy
cao v s chuyn ng
hn n
- S va chm mnh
vo van v vng m
ph v size ht
a sp ng ha
vo khoang trao
i nhit h t
o

chun b cho
cycle tip theo
B. PH NG PHP TO H NANO -NH TNG
Nh vy, t c hiu qu ng ha cao, ta thng xem xt
cc s liu sau:
p sut
Nhit
Thit k ca mt m (seat) v vng m
Lu lng
S cycle.

Cc my ng ha p cao c th t dung lng t 55
4.500 lt ty theo qui m.
Bm cao p dng mt piston chy bng mt trong mt
hnh tr bng thp c th nng p ln n 40.000 psi.
Qu trnh ny sinh ra lng nhit ng k nn cc piston
v xi-lanh phi c lm mt bng nc.
B. PH NG PHP TO H NANO -NH TNG
M phm
Y hc
Thc phm
Kem dng m
Nh tng dng tc
Nh tng lm trng da
Sa sn chc da Sa phc hi cho da
Phn b nhiu trong c th ngi v c trong t nhin
L yu t kt hp (cofactor) ca t nht 3 enzyme ti ti th ca mi t bo to ra ATP
(adenosin triphosphat) cho nng lng
L cht chng oxy ha

The inner core
consisting of any
oil

Drug or nutrient
molecules within
the core

The emulsifier
layer surrounding
the nano-particle.



MicroFluidics Technology Fair
Thuc khng vi trng
(Antiambiral emulsion)
Vc-xin cht nhn
(mucosal vaccines)
K thut cy ghp t bo
(cell culture technology)

Cht ty u khng c hi
(non-toxic disinfectant
cleaners)

Phng nga bnh
(prophylatic in bio-terrorism
attack)
Prepared by Holly R-Fischer, MFA,
For NanoBio: 01/13/2009
Anti-oxidant synergy formation (ASF) studies (in vivo)
Nude Mice
since they lack a fully-functional immune system
Injection of Cancer Cells
by subcutaneous injection of Mouse or Human Cancer
cells (300,000 cells /ml)
Injection of ASF solution
once tumors were detected
Measure the tumor diameter
quantified daily in accordance with the longest diameter
The neuroblastoma in the nude mice
ASF
Nano-emulsion
Control
(no treatment)
Tumor
No Tumor
Subcut inj Subcut inj Transdermal
- 65% - 63%
- 4%
Subcut Injection vs Topical Delivery of ASF containing-
nanoemulsions on neuroblastomainduced tumor growth rate

Thc phm
Nanoemulsions are stable dispersions which do not agglomerate
and which demonstrate antimicrobial activity
Microemulsion versus Nanoemulsion of Soy Protein
Homogenized Nanoemulsified
Gram + Staph Aureus Bacteria
Staph Aureus Control Staph aureus streaked
empty nanoemulsion

XIN CHN THNH CM N
C V CC BN THEO DI