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DISPERSE SYSTEMS
The
Each
Dispersed Systems
Dispersed Systems
Physical stability
Stokes Law
v
Stability
Particles need to come into contact
(collide) to coalesce
Therefore, higher concentrations (via
creaming/settling) promote coalescence or
caking
DISPERSE SYSTEMS
Calculations
Calculations
Particle
size determination:
Coalescence
Dosing uniformity
Importance
Dispersion
Coarse dispersion 10 to 50 m
Fine dispersion 0.5 to 10 m
Colloidal 1 nm to 0.5 m
Suspensions
Marketed preparations:
ready-to-use
dry powders which must be reconstituted before administration
SUSPENSIONS
Suspensions: Advantages
Desirable Features
flock
cake
Sedimentasi
Flokulasi
Deflokulasi
Agglomerasi
Caking
2r 2 ( d1 d 2 ) g D 2 ( d1 d 2 ) g
v
9
18
1.
2.
3.
Theory of Sedimentation
FACTORS TO BE CONSIDERED
Particle size
Density of the vehicle
-polyethylene glycol
-polyvinyl pyrolidone
-glycerin
-sorbitol
-sugar.
State
Rate of settling
Sedimentation
volume
Nature
Flocculated
Fast
High
Porous, easy to
redisperse
Deflocculated
Slow
Low
Compact, difficult
to redisperse
Sedimentation Volume
V = Vu /V0 ; ideally, V should be equal to 1.0
Thixotropic suspension
A
Formulation of suspension
wetting agent
dispersants
flocculating agent
thickeners
pH control agent
osmotic agent
coloring agents
preservatives to control microbial growth
liquid vehicles
METHODS OF PREPARATION
(1)
(2)
Wetting agent
Controlled flocculation
The flocculating power increases with the valency of the ions. As for
example, calcium ions are more powerful than sodium ions because
the velency of calcium is two whereas sodium has valency of one.
Structured vehicle
Examples :
Antacid oral suspensions
Antibiotics for oral suspension
Parenteral penicillin suspension
(a)
(b)
(c)
(d)
crushers and
shredders
hammer mills
colloid mills
fluid energy mills
Drug
Suspending agent
Wetting agent
Buffer
Preservative
Also, coloring, sweetening, and flavoring agents
Suspending Agent
Wetting Agent
Tween 80
Span
Alkohol
Propilenglikol
Dioktil Na Sulfosuksinat
Na Lauril Sulfat
untuk sediaan
oral
untuk obat
luar
Preservative
Asam benzoat
Na benzoat
: 0,1 %
: 0,1 %
Compounding of Suspensions
EVALUATION OF SUSPENSIONS
Evaluasi sediaan
Parameter
Viskositas
pH
Stabilita fisik
Stabilita kadar
Evaluasi sediaan
Penentuan pH sediaan
Penentuan volume sedimentasi
Evaluasi sediaan
Parameter yang diperhatikan formulasi dry sirup
Parameter
Flow granul/serbuk
baik
Homogenitas
Stabilita fisik/kadar
Setelah rekonstitusi
sampai
Make clear to the patient that the headspace is not because they
have been cheated of drug, but rather to allow room to shake the
mixture.
MANUFACTURING DIRECTIONS
1.
2.
3.
4.
5.
6.
Cont
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Add sugar syrup and mucilage to the mixer. Rinse the container of mucilage
with 15 g of item 13 and add the rinsings to the mixer. Cool to 25.C while
mixing.
Add item 1 dispersion to the mixer. Rinse the container of dispersion with
15 g of item 13 and add rinsings to the mixer. Check the suspension for
uniformity of dispersion.
Mix for additional 5 minutes at 18 rpm, vacuum 0.5 bar if required.
Add item 8 to the mixer and mix for 10 minutes. Dissolve item 10 in 7 g of
item 13 and add to the mixer.
Disperse item 11 in 7 g of item 13 and add to the mixer. Add item 12 to the
mixer.
Add cold item 13 (25.C) to make up the volume up to 1.0 L.
Homogenize for 5 minutes at low speed under vacuum 0.5 bar, 18 rpm,
temperature 25.C.
Check the dispersion for uniformity.
Check the pH. Limit 5.7 0.5 at 25.C. If required adjust the pH with 20%
solution of Citric Acid or Sodium Citrate.
Transfer the suspension through 630 micron sieve after mixing for 5
minutes at 18-20 rpm, temperature NMT 25.C, to the stainless steel storage
tank.
Acetaminophen Suspension
1.
2.
1.
2.
1.
2.
3.
4.
5.
6.
References
Emulsions
Definition
An emulsion is a dispersion in which the
dispersed phase
is composed of small globules of a liquid
distributed
throughout a vehicle in which it is immiscible.
dispersion
B phase
A phase
Emulsion
solution
Types
Types of
of emulsions
emulsions
Basic types
O/W
W/O
multiple
W/O/W
InternalExterna InternalExterna
phase l phase phase l phase
oil-in-water
water-inoil
O/W/O
Water inoil-inwaterOil-in-waterin-oil
Types of Emulsion
m
Water
Oil
Oil-in-water emulsion
Water-in-oil emulsion
Multiple Emulsions
m
Water
Oil
Water-in-oil-in-water emulsion
Oil-in-water-in-oil emulsion
Emulsion Size
0.5 m
0.5-1.5 m
1.5-3 m
>3 m
<
Surface active agents have a certain affinity for both polar &
nonpolar solvents
Amphiphilic nature adsorb at interfaces
At a concentration that is characteristic of each amphiphile, these
molecules will aggregate to produce micelles
water
oil
oil
W/O
O/W
Hydrophil head
Lipophil chain
emulsifier
The basic requirements for emulsifier
Types of emulsifier
Emulsifying mechanism
Type of emusifier
1. high molecular
compound
2. surfactants
3. solid powder
2 . surfactants
anionic
anionic surfactants
surfactants
Active
part -
Na
polarity
hydrophili
c
Nonpolarity
hydrophobic
nonionic
nonionic
surfactants
surfactants
Sorbitan W/O type
span20 40 60 80
Polyoxyethylene sorbitan monolaurate O/W
type
tween20 40 60 80
Polyxyethylene fatty acid ester
Myrij O/W type
Myrij 45 49 52
Finely
Finely divided
divided solids
solids
can
can be
be aggregated
aggregated at
at
surface
surface between
between oil
oil and
and water
water to
to form
formsolid
solid
particle
particle membrane
membrane
contact
contact angle
angle of
of solid
solid powder
powder with
with water
water phase
phase
determine
determine the
the types
types of
of emulsions
emulsions
<90
<90 O/W
O/W
>90W/O
>90W/O
Emulsification
Emulsifier
EMULSIONS
Theories of Emulsification:
1) Surface Tension Theory:
- lowering of interfacial tension.
2) Oriented-Wedge Theory:
- mono molecular layers of emulsifying agents are
curved around a droplet of the internal phase of the
emulsion.
3) Interfacial film theory:
- A film of emulsifying agent prevents the contact and
coslescing of the dispersed phase.
Emulsifying Agents:
1) Carbohydrate Materials:
- Acacia, Tragacanth, Agar, Pectin. o/w emulsion.
2) Protein Substances:
-Gelatin, Egg yolk, Caesin o/w emulsion.
3) High Molecular Weight Alcohols:
- Stearyl Alcohol, Cetyl Alcohol, Glyceryl Mono stearate o/w emulsion,
cholesterol w/o emulsion.
4) Wetting Agents:
Anionic, Cationic, Nonionic
o/w emulsion
w/o emulsion
5) Finely divided solids:
Bentonite, Magnesium Hydroxide,
Aluminum Hydroxide o/w
emulsion
Additives of emulsions
1. coemulsifier
2 preservatives
3 antioxidants
4. sweeting agent
Tujuan formulasi
R/ Parafin cair
Setilalkohol
Emulgator
Pengawet
Air ad
25
20
2
0,2
100
HLB butuh
Parafin cair
25
25/45 x 8 = 4,5
Setilalkohol
20 15
20/45 x 15 = 6,7
Jumlah
45
11,2
Methods
Methods of
of emulsion
emulsion preparation
preparation
Preparation of Emulsions
Preparation method
1 hand-made method
1 dry gum
method
water
oil emulsifer
2 wet gum method
oil
water emusifier
direct
mixture
method
oil3water
emulsifer
emulsio
n
emulsio
n
emulsion
Methods of Manufacture
Recall
goal
Overcome
surface tension
Add energy by creating shear gradient within
the liquid
Shear gradient
Emulsions:
Different ways of production
Hot/HotProcess
Both,fatandwaterphaseareheatupseparatelytoacertain
temp.(7085C).Thehotoilphaseandthehotwaterphase
werecombinedundervacuumatthehightemperatureand
emulsified.Emulsificationisdonebytherotorstatorsystem.
Subsequentlytheproductiscooleddown.
Hot/ColdProcess
Thefatphaseisheatuptoatemp.(app.10Cabovethehighest
meltingpointoftheingredients).Thehotfatphaseandthecold
waterphasewerecombinedundervacuumandemulsifiedatthe
mixingtemperature.Subsequentlytheproductiscooleddown.
Advantage:shortercoolingtimes,savingofenergy
Basic Methods
Mechanical
stirrers
Homogenizers
Colloid mills or Rotor-stator
Ultrasonifiers
Mechanical Stirrers
Homogenization
Ultrasonic Homogenizer
Vacuum Homogenizer
Colloid Mills
1000-20000
rpm
High sheer rates
Heat build up a problem
Ultrasonification
Sound
Cooling downto 40 C
Homogenizer interval: Run 1500rpm 30s
Pause 150s
Deaeration;
Temperature 40 C; Vacuum 50 mbar
Discharge;
Temperature 40 C
Homogenizer 1000 rpm
Flocculation
The association of particles within an emulsion to
form large aggregates, which can be easily be
redispersed upon shaking.
O /W
phase
inversion
O/W type
The
The reason
reason for
for phase
phase inversion
inversion
property of emulsifier
phase volume ratio
W/O type50%~60%
O/W type90%
W/O
irreversible
irreversible
coalescence
the mechanical of electrical barrier is insufficient
to prevent the formation of progressively larger
droplets.
breaking or creaking
The coalescence of the globules of the internal
phase and the seperation of that phase into a layer
Coalescence and breaking are irreversible
EMULSIONS
Stability of Emulsion:
An emulsion is considered to be physically unstable if :
a) The internal phase tends to form aggregates of globules.
b) Large globules or aggregates of globules rise to the top or
fall to the bottom of the emulsion to form a concentrated
layer of the internal phase.
c) If all or part of the liquid of the internal phase becomes
"unemulsified on the top or bottom of the emulsion.
Emulsion stability
emulsions
w/o/w
stability issues
Microemulsions
Multiple Emulsions
Emulsions
The
Preperation
MICROEMULSIONS
Pharmaceutical Applications
of Microemulsions
the ability to concentrate and localize significant
amounts of both oil and water-soluble materials
the rate of absorption of cyclosporin is more rapid and
less variable than it is with the conventional oily
dispersion.
Microemulsions have also been used for topical
delivery where they increase drug absorption.
For example, cetyl alcohol, which is commonly used as an
emulsifier in lotions and creams, is absorbed faster and
deeper into the skin when formulated as a component of a
microemulsion.
1.
2.
3.
4.
5.
6.
7.
Pemeriksaan BJ sediaan
Pemeriksaan ukuran partikel
Penentuan viskositas dan sifat alir
Volume sedimentasi
EMULSIONS
1.
2.
3.
Water Solutions
A solution is formed in water as a solvent
Preparation of Solutions
Weigh the sample
Dissolve the sample
filtrate
quality test
package
Aromatic Waters
Aromatic Waters are saturated solutions (unless otherwise
specified) of volatile oils or other aromatic or volatile
substances in distilled water.
Preparation method of Aromatic Waters
1. Distillation
2. Solution
3.Dilution
Syrups
Components
Sugar
Ora-Sweet plus
Not absorbed
Has syrup like and feel
Good for diabetic patients
85 g sucrose qs 100 mL
No preservatives needed
High osmotic pressure like honey
Sucrose solubility 1 g in 0.5 mL water
Syrup Preservation
Three
Methods
Components Cont.
Flavorant
Colorant