Coarse Dispersions
PhD Halina Falfushynska
2
Definition
• A Pharmaceutical suspension is a coarse dispersion
in which internal phase is dispersed uniformly
throughout the external phase.
• The internal phase consisting of insoluble solid
particles.
• The external phase (suspending medium) is generally
aqueous in some instance, may be an organic or oily
liquid for non oral use.
Suspensions
Dispersions containing coarse
particles, usually 10 to 50 um
in size, are referred to as
coarse dispersion.
Dispersions containing particles of
smaller size are termed fine
dispersions (0.5 to 10 um)
Suspensions
Classification
• Based On General Classes
Oral suspension
Externally applied suspension
Parenteral suspension
• Based On Proportion Of Solid Particles
Dilute suspension (2 to10%w/v solid)
Concentrated suspension (50%w/v solid)
• Based On Electrokinetic Nature Of Solid Particles
Flocculated suspension
Deflocculated suspension
• Based On Size Of Solid Particles
Colloidal suspension (< 1 micron)
Coarse suspension (>1 micron)
Nano suspension (10 ng)
5
• Advantages and Disadvantages due to viscosity
of
medium
312 PHT
Advantages
• High viscosity inhibits the crystal growth.
• High viscosity prevents the transformation of metastable
crystal to stable crystal.
• High viscosity enhances the physical stability.
Disadvantages
• High viscosity hinders the re-dispersibility of the
sediments
• High viscosity retards the absorption of the drug.
• High viscosity creates problems in handling of the
material during manufacturing.
Physical Features of the Dispersed Phase
of a Suspension
Good pharmaceutical suspensions, the particle
diameter is between 1 to 50.
Particle size reduction is generally accomplished
by dry-milling prior to the incorporation of the
dispersed phase into the dispersion medium.
One of the methods of producing fine drug
powders of about 10 to 50 um size is
micropulverization.
For still finer particles, under 10 um, the process
of fluid energy grinding, sometimes referred to as
jet-milling or micronizing.
Dispersion Medium
The
amount of the suspending
agent must not be such to
render the suspension too
viscous to agitate (to
distribute the suspensoid) or to
pour. The study of the flow
characteristics is termed
rheology
Rheological properties
• Viscosity - is a measure of the resistance of
a fluid which is being deformed by either tensile stress
• Flexibility- the ability to recover the form of matter
(volume) after deformation. Flexibility causes the
alignment marks of finger pressure on the surface of
plastiline.
• Plasticity - the opposite of the elastic properties of the
substance taken and permanent deformation after
removing the load. Due to the plasticity of plastiline
retain fashioned.
• Elasticity - the property of matter experience
significant deformation without destroying the
structure.
Standard laboratory viscometers for
liquids
Ostwald viscometers measure the
viscosity of a fluid with a known
density.
Falling Piston Viscometer
Suspensions quantified by
sedimentation volume (f)
Degree of flocculation (β)
Sedimentation volume is a ratio of the final or
ultimate volume of sediment (Vu) to the original
volume of sediment (VO) before settling.
Sustained-Release Suspension
• In liquid preparations (suspensions) of the
coated particles, the drug remains adsorbed onto
resin, but slowly released by the ion-exchange
process when taken into gastrointestinal tract.
The use of a combination of ion-exchange resins
complex and particle coating is called
Pennkinetic system.
• Examples:
▫ Hydrocodone polistirex =Tussionex Pennkinetic
Extended-Release Suspension
Characteristics of Oral Suspension
• Particles should be small uniform
sizes that do not settle rapidly
• The particles that do settle to the
bottom of the container should not
pack in to a hard cake and should
be re-dispersed
completely and
evenly with a minimum amount of
agitation
Characteristic of Suspensions
Should
not be too viscous to
pour freely from the mouth of
the bottle
Should have an agreeable odor,
color and taste and must not
decomposed or support mold
growth during storage
Must have therapeutic efficacy
Characteristic of Suspensions
•Suspensions for injections
must contain particles size
such that they can pass
freely through the syringe
needle called
“syringeability”.
Characteristic of Suspensions
Ophthalmic suspension
should be formulated such
that the particles do not
exceed 10 microns.
Below this size, the patient
experiences no pain when
instilled into the eyes.
Dispersion Medium
• Suspending agents are added to the dispersion
medium to lend its structure to assist in the
suspension of the dispersed phase
• Examples:
Carboxymethylcelulose
Methylcellulose
Microcrystalline cellulose
Polyvinyl pyrolidone,
Xanthan gum
Bentonite
Example of Preparation
Aluminum Hydroxide Compressed
Gel
326.8 g
Sorbitol Solution
282.0 mL
Syrup
93.0 mL
Glycerin
25.0 m
Methylparaben
0.9 g
Propylparaben
0.3 g
Flavor
q.s
Purified water, to make
1000.0 mL
USE: ANTACID
Examples of Oral Suspensions by Category
Antacids
Alumina, Magnesia and Simethicone - Mylanta liquid
Magaldrate Oral Suspension - Riopan Oral Suspension
Magnesia and Alumina Oral - Maalox Suspension
Aluminum Hydroxide and Magnesium Carbonate - Gaviscon
liquid
Anthelminitics
Pyrantel Pamoate - Antiminth Oral Suspension
Thiabenzadole Oral Suspension - Mintezol Oral Suspension
Antibacterial
(Antibiotics)
Chloramphenicol Palmitate - Chloromycetin Palmitae Oral
Suspen.
Ertythromycin Estolate - Ilosone Oral Suspension
Antibacterial (non- Methenamine Mandelate - Mandelamine Suspension/Forte
antibiotic Anti- Sulfamethoxazole and Trimethoprim - Bactrim, Septra
Suspension
infectives)
Sulfamethoxazole - Gantanol Suspension
Sulfisoxazole Acetyl Oral Suspension- Gantrisin Syrup/Pedia
Anticonvulsants
Pimidone Oral Suspension - Mysoline Suspension
Antidiarrheal
Bismuth Subsalicylate - Pepto-Bismol liquid
Examples of Oral Suspensions by Category
Antiflatulent
Simethicone Oral Suspension - Mylicone
Drop
Antifungals
Nystatin Oral Suspension - Nystatin Oral
Suspension
Griseofulvin Oral Suspension -Grifulvin
Oral Suspension
Antihypertensive
Methyldopa Oral Suspension - Aldomet
Oral Suspension
Antipsychotics, Sedatives,
Antiemetic
Hydroxyzine Pamoate Oral Suspension
- Vistaril Oral Suspension
Thioridazine Oral Suspension - MellarilS Oral Suspension
Diuretic
Chlorothiazide Oral Suspension - Diuril
Oral Suspension
Nonsteroidal Anti-inflammatory
Indomethacin Oral Suspension - Indocin
Oral Suspension
Sample Products
CEFIXIME
TERGECEF GRANULES
FOR SUSPENSION
PARACETAMOL
BIOGESIC SUSPENSION
CARBOCISTEINE
SOLMUX FORTE SUSPENSION
EMULSIONS
• The word emulsion, came from emulgio,
“meaning to milk out”.
• 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.
Emulsion terminology
• The dispersed phase is referred to as the
Internal phase
• The dispersion medium as the External or
Continuous phase
• Emulsions having an oleaginous internal
phase and aqueous external phase are referred
to as oil-in-water (o/w) emulsions
• Emulsions having an aqueous internal phase
and an oleaginous external phase are termed
water-in- oil (w/o) emulsions.
Theories of Emulsification
1.
2.
3.
4.
Surface Tension Theory
Oriented-Wedge Theory
Plastic or Internal Film Theory
Viscosity Theory
Oriented-wedge Theory
• Assumes monomolecular layers of emulsifying
agent curved around a droplet of the internal
phase of the emulsion.
• It is based on the presumption that certain
emulsifying agents orient themselves about and
within a liquid in a manner reflective of their
solubility in that particular liquid.
• An emulsifying agent having a greater
hydrophilic character than hydrophobic character
will promote an O/w emulsion and a W/O
emulsion results through use of more
hydrophobic than hydrophilic emulsifiers.
Plastic or Interfacial-Film Theory
• Places the emulsifying agent at the interface between
the oil and water, surrounding the droplets of the
internal phase as a thin layer of film adsorbed on the
surface of the drops.
• The film prevents the contact and the coalescence of
the dispersed phase, the tougher and more pliable
the film, the greater the stability of the emulsion.
Viscosity Theory
• States that the viscosity of an emulsion aids
emulsification by the mechanical hindrance to
coalescence of the globules although it is not the
cause of emulsification.
Emulsifying Agents
 These materials form hydrophilic
colloids when added to water and
generally produced O/W emulsions.
Acacia is most frequently use.
Tragacanth and Agar - thickening
agents in Acacia emulsified products.
 These substances produce O/W
emulsions. The disadvantage of
gelatin is that the emulsion prepared
from it are too fluid.
Natural
Emulsifying
Agents
High
Molecular
Weight
alcohols


These materials employed primarily as
thickening and stabilizing agents for O/W
emulsions such as lotion and ointments
Cholesterol may also be employed in
externally used emulsion and promote W/O
emulsions.
Carbohydrates:
 acacia,
 tragacanth
 agar,
 chondrus,
 pectin
Proteins
 gelatin,
 egg yolk,

casein



stearyl alcohol,
cetyl alcohol,
glyceryl
monostearate
Emulsifying Agents
Finely
Divided
Solids
These materials generally form
O/W emulsions when the
insoluble material is added to the
aqueous phase if there is greater
volume of the aqueous phase
than of the oleaginous phase
Colloidal clays including
Bentonite,
Magnesium hydroxide
Aluminum hydroxide
Synthetic
(wetting agents), which may be
Anionic, Cationic, Nonionic
Anionic:
triethanolamine oleate and
sodium lauryl sulfate
Cationic:
benzalkonium chloride
Nonionic:
sorbitan
esters
(span);
polyethylene
glycol
400
monostearate; polyoxyethylene
sorbitan esters (Tweens)
Qualities Required for Emulsifiers
▫
▫
▫
▫
▫
▫
Must be compatible with other ingredients in the
formula
Must not interfere with the stability and efficacy of
the therapeutic agent
Must be stable to microorganisms
Must be non-toxic
Must possess little or no odor, taste or color
Must promote emulsification and maintain stability
of the emulsion for intended shelf-life
The HLB or Hydrophilic- Lipophile
Balance
• Each emulsifying agents has a hydrophilic portion
(water-loving) and a lipophilic portion (oil-loving)
with one or other being more or less predominant and
influencing
• A method indicative of the substances polarity devised
and lead to the assigning of an HLB value for each
agent. The usual range is between 1 to 20.
• Materials that are highly polar or hydrophilic
have assigned higher numbers than materials that are
less polar and were lipophilic.
Methods of Preparation
1.
2.
3.
4.
5.
6.
Continental or Dry gum method
English or wet gum method
Bottle or Forbes bottle method
Auxiliary method
In SITU soap method
Microemulsions
Continental or Dry gum method
+O+W)
(G
•
The method is also referred to as the “4:2:1”
method because for every 4 parts (volumes) of
oil, 2 parts of water and 1 part of gum are
added in preparing the initial or primary
emulsion.
•
For instance, if 40 mL of oil are to be
emulsified, 20 mL of water and 10 g of gum
would be employed, with additional water or
other formulation ingredients being added
afterward to the primary emulsion
Bottle or Forbes Bottle Method
(G+O+W)
• For the extemporaneous preparation
of emulsions from volatile oils or
oleaginous substances of low
viscosities, the bottle method is
used. (2:2:1)
Auxiliary Methods
An emulsion by either the wet gum or dry
gum methods can generally be increased in
quality by passing it through a hand
homogenizer.
In this apparatus, the pumping action of the
handle forces the emulsion through a very small
orifices which reduces the globules of the
internal phase to about 5 um and sometime less
In SITU Soap Method
• Two types of soap developed by this method are
Calcium soaps and Soft soaps.
• Calcium soaps
water - in - oil emulsions which contain
certain vegetable oil (e.g. Oleic acid) in
combination with lime water
( Syn: Calcium
Hydroxide Solution USP) and prepared by
mixing equal volumes of the oil and lime water
Microemulsions
•
•
•
Thermodynamically stable, optically
transparent, isotropic mixtures of a biphasic
oil-water system stabilized with surfactants.
The diameter of droplets in a microemulsion
may be in the range of 100 A (10 microns) to
1000 A whereas in a microemulsion the
droplets may be 5000 angstroms in
diameter.
Both O/W and W/O microemulsions may be
formed spontaneously by agitating the oil and
water phases with carefully selected surfactant.
Terminology
Flocculation
- is the joining together of globules to form large clumps or floccules which
rise or settle in the emulsion more rapidly than do the individual
particles
Creaming
is the rising (upward creaming) or settling (downward creaming) of
globules or floccules to form a concentrated layer at the surface or to
the bottom of the emulsion
Coalescence and
breaking
unlike creaming, the coalescence of globules and the subsequent breaking
of an emulsion are irreversible processes. In creaming, the globules
are still surrounded by a protective coating or sheath of emulsifying
agent and may redispersed simply by agitating the product.
Deterioration by
Microorganism
Molds, yeast and bacteria may bring about decomposition and
contamination of the emulsion. Preservatives should be more
fungistatics than bacteriostatic
Miscellaneous
Physical and
Chemical
Change
Light and rancidity affect the color and the odor of oils and may destroy
their vitamin content. Freezing and thawing and high temperature
result in the coarseness and breaking of an emulsion.
Terminology Related To Gels
Imbibition
is taking up of a certain amount of liquid without a measurable
increase by a gel with an increase volume.
Swelling
is the taking up of a liquid by a gel with an increase in volume. Only
those liquid that solvate a gel can cause swelling. The swelling
of protein gels is influenced by pH and thepresence of
electrolytes.
Syneresis
is when the interaction between particles of the dispersed
phase
becomes so great than on standing, the dispersing medium is
squeezed out in droplets and the gel shrinks. Syneresis is a form
of instability in aqueous and nonaqueous gels
Thixotrophy
is a reversible gel-sol formation with no change in volume or
temperature-a type of non-Newtonian flow.
Xerogel
is formed when the liquid is removed from a gel and only the
framewok remains. Examples: gelatin sheet, tragacanth ribbons
and acacia tears