AUF CAMP – PHARMACY DEPARTMENT

PHYSICAL PHARMACY (LECTURE)

Module 5: Heterogenous Systems
Lecturer: Mairre Louie D. Punsalan

OUTLINE CLASSIFICATION OF DISPERSED SYSTEMS BASED ON

Colloidal Dispersions PARTICLE SIZE
Coarse Dispersions Molecular Dispersion
Interfacial Phenomena  Particle size: less than 1nm
 Characteristics of system
OBJECTIVES  Invisible in electron microscope
 Differentiate between different types of colloidal systems and  Pass through ultrafilter and semipermeable
their main characteristics. membrane
 Describe what pharmaceutical suspensions are and what roles  Undergo rapid diffusion
they play in the pharmaceutical sciences.  Examples: oxygen molecules, ordinary ions, glucose
 Discuss the factors that affect the stability of suspensions and
explain flocculation. Colloidal Dispersion
 Understand the terms surface tension and interfacial tension  Particle size: from 1nm to 0.5um (micrometer)
and their application in pharmaceutical sciences.  Characteristics of system
 Not resolved by ordinary microscope (although may
be detected under ultramicroscope)
COLLOIDAL DISPERSIONS  Visible in electron microscope
 Pass through filter paper
Introduction  Do not pass semipermeable membrane
 Important to understand the theory and technology of dispersed  Diffuse very slowly
systems  Examples: colloidal silver sols, natural and synthetic polymers,
 Understand the behavior of pharmaceutical dispersions cheese, butter, jelly, paint, milk, shaving cream, etc.
 Difference in dispersed phase (based on size, not composition)
Coarse Dispersion
Molecular Dispersions – homogenous in character and form true solutions  Particle size: greater than 0.5um (micrometer)
 Characteristics of system
 Visible under microscope
 Do not pass through normal filter paper
 Do not dialyze through semipermeable membrane
 Do not diffuse
 Examples: grains of sand, most pharmaceutical emulsions and
suspensions, red blood cells
*1nm (nanometer) = 10 -9m; 1um (micrometer) = 10 -6m

COLLOIDS

 A system in which particles of colloidal size (1nm – 0.5um) are

dispersed in a continuous phase of a different composition
 Types of Colloidal Systems
 Lyophilic Colloids
 Lyophobic Colloids
 Association Colloids
Yellow  Plasma: water (91.5%), proteins (7%), other solutes (1.5%)
White  “Buffy coat” composed of white blood cells and platelets TYPES OF COLLOIDAL DISPERSIONS
 White blood cells: lymphocytes, granulocytes, monocytes Dispersion Dispersed
Colloid Type Examples
 Granulocytes: basophils, neutrophils, eosinophils Medium Phase
Red  Red blood cells (coarse particles, coarse dispersion) Solid Solid Solid sol Pears, opals
 RBCs carry oxygen to the cells and tissues Solid Liquid Solid emulsion Cheese, butter
 Size: 6um (micrometer) in diameter, 2um in width Solid Gas Solid foam Pumice, marshmallow
Liquid Solid Sol, gel Jelly, paint
 WBCs are also considered coarse dispersions
Liquid Liquid Emulsion Milk, mayonnaise
Liquid Gas Foam Whipped and shaving cream
Serum albumin, a component of blood, is considered also a colloidal Gas Solid Solid aerosols Smoke, dust
dispersion with particles having the size of greater than 1um (micrometer). Gas Liquid Liquid aerosols Clouds, mist, fog

Dispersed Systems LYOPHILIC COLLOIDS

 Consists of:
 Dispersed phase – particulate matter (e.g., nutrients
such as peptides, proteins, and glucose in the blood
 true solution); may range in different sizes from
the particles of atoms and molecules (millimeters or
micrometer)
 Dispersion medium – or continuous phase,
distributes the dispersed phase; can be vehicle or
solvent (e.g., plasma in the human blood)
 Classification of Dispersed Systems (based on particle size)
 Molecular Dispersions
 Colloidal Dispersions
 Coarse Dispersions
 Systems containing colloidal particles that interact to an
appreciable extend with the dispersion medium (e.g., colloidal
dispersions or sols)
 Sols are colloids made up of very small particles in
a continuous liquid medium
 French or Latin: “lyo” – to loosely interact or to lose (solvent-
loving); “philia” – love
 Usually obtained by dissolving material in solvent
 Pharmaceutical Examples:
 Dissolution of acacia/gelatin in water
 Celluloid in amyl acetate

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 5: Heterogenous Systems
Lecturer: Mairre Louie D. Punsalan

 Solvation – attachment of solvent molecules to the molecules
of dispersed phase
 Hydration – water is the dispersion medium
 Hydrophilic sols – gelatin, acacia, insulin, albumin
(organic molecules in aqueous dispersion media)
 Lyophilic colloids (specificity)
 Lipophilic colloids – rubber, polystyrene
 Dissolved in non-aqueous organic
solvent
LYOPHOBIC COLLOIDS
 Have little attraction for the dispersion medium (solvent-hating)
 Absence of a solvent sheath around the particle
 Examples: inorganic particles in water
 Gold, silver, sulfur, arsenous sulfide, silver iodide
 Special Methods of Preparation
 Dispersion Methods – reducing particle size for
greater attraction to the solvent
 Condensation Methods – aggregate particles and in
the colloidal size range
ASSOCIATION COLLOIDS
 Also known as amphiphilic colloids
 Amphiphiles or surface-active agents – have two distinct
regions of opposing solution affinities  can help in the
solubility of the colloids and their dispersion
 Micelles
 Aggregates containing 50 or more monomer
 Example: detergents, cosmetic products
 Critical micelle concentration (CMC) –
concentration of the monomer in which the micelles
are formed
 Aggregation number – number of monomer units
aggregated to form a micelle
COMPARISON OF PROPERTIES OF COLLOIDAL SOLS
Lyophilic
 Dispersed phase consists generally of large organic molecules
lying within colloidal size range
 Molecules of dispersed phase are solvated, i.e., they are
associated with the molecules comprising the dispersion
medium
 Molecules disperse spontaneously to form colloidal solution
 Viscosity of the dispersion medium ordinarily is increased
greatly by the presence of the dispersed phase; at sufficiently
high concentrations, the sol may become a gel; viscosity and
gel formation are related to solvation effects and to the shape of
the molecules, which are usually highly asymmetric
 Dispersions are stable generally in the presence of electrolytes;
they may be salted out by high concentrations of very soluble
electrolytes; effect is due primarily to desolvation of lyophilic
molecules
Association (Amphiphilic)
 Dispersed phase consists of aggregates (micelles) of small
organic molecules or ions whose size individually is below the
colloidal range
 Hydrophilic or lipophilic portion of the molecule is solvated,
depending on whether the dispersion medium is aqueous or
nonaqueous
 Colloidal aggregates are formed spontaneously when the
concentration of amphiphile exceeds the critical micelle
concentration
 Viscosity of the system increases as the concentration of the
amphiphile increases, as micelles increase in number and
become asymmetric
 In aqueous solutions, the critical micelle concentration is
reduced by the addition of electrolytes; salting out may occur at
higher salt concentrations
Lyophobic
 Dispersed phase ordinarily consists of inorganic particles
 Little if any ineraction (solvation) occurs between particles and
dispersion medium
 Material does not disperse spontaneously, and special
procedures therefore must be adopted to produce colloidal
dispersion
 Viscosity of the dispersion medium is not greatly increased by
the presence of lyophobic colloidal particles, which tend to be
unsolvated and symmetric
 Lyophobic dispersions are unstable in the presence of even
small concentrations of electrolytes; effect is due to
neutralization of the charge on the particles; lyophilic colloids
exert a protective effect

PROPERTIES OF COLLOIDS

Optical Kinetic Electrical

Brownian Motion
Faraday-Tyndall Effect
Diffusion Electrokinetic
Electron Microscope
Sedimentation Phenomena
Light Scattering
Viscosity

FARADAY-TYNDALL EFFECT

 When a strong beam of light

Traditional Cleansers
The cleaning molecules in traditional
cleansers work alone to dissolve
makeup so you have to rub your face
harshly and rinse with water to
completely clean your skin.
The Micellar Difference
The micelle molecules in micellar
cleansing water cluster together to lift
dirt, oil, makeup and impurities on
contact. No rinsing, no harsh rubbing –
it is an entirely different way to cleanse.
is passed through a colloidal
sol, a visible cone, resulting
from the scattering of light
by the colloidal particles, is
formed.
 Can be observed also to examine the light points using an
ultramicroscope

Renhart M. Salas, fRPh 2|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 5: Heterogenous Systems
Lecturer: Mairre Louie D. Punsalan

ELECTRON MICROSCOPE Zeta Potential

 Capable of yielding pictures of the actual particles, even those
approaching molecular dimensions
 Widely used to observe the size, shape, and structure of
colloidal particles
 High resolving powder allows observation of smaller particles
as compared to an ordinary microscope  details, size, shape
 Also known as electrokinetic potential
 Difference in potential between the surface of the tightly-bound
layers and the electroneutral region of the dispersion
 Has more application in pharmacy (e.g., decreased zeta
potential results to flocculation)
ELECTROKINETIC PHENOMENA

LIGHT SCATTERING  The movement of a charged surface with respect to an adjacent

 Depends on Faraday-Tyndall effect
 Widely used to determine MW (molecular weight) of colloids,
size and shape of particles
 Can be described in terms of turbidity, which can be expressed
as the intensity of scattered light in all directions
 At a given certain concentration of the dispersed phase, the
turbidity can be proportional to the molecular weight (MW) of
the lyophilic colloid (T ~ MW)
BROWNIAN MOTION
 Random movement of colloidal particles
 Erratic motion – observed with particles as large as about 5um
due to bombardment of the particles by the molecules of the
dispersion medium
 Motion of molecules cannot be observed – too small
 Velocity of particles increases with decreasing particle size;
increasing viscosity of medium, decreases and/or stops
Brownian movement (viscosity is the resistance to flow)
liquid phase is the basic principle underlying four electrokinetic
phenomena:
 Electrophoresis
 Electroosmosis
 Sedimentation potential
 Streaming potential
Electrophoresis
 One of the mostly used biotechnology today
 Movement of a charged particle through a liquid under the
influence of an applied potential difference
 An electrophoresis cell fitted with two electrodes contains the
dispersion. When a potential is applied across the electrodes,
the particles migrate to the oppositely charged electrode.
 Makes use of a gel and allow the charged particles to move 
analyze certain DNA and RNA

DIFFUSION

 Particles diffuse spontaneously from a region of higher

concentration to one of lower concentration until the
concentration of the system is uniform throughout
 Diffusion is a direct result of Brownian movement
 Equation: Fick’s law

OSMOTIC PRESSURE

 The osmotic pressure, π, of a dilute colloidal solution is

described by the van’t Hoff equation

π = cRT, where c is the molar concentration of the solute

SEDIMENTATION

 The velocity, v, of sedimentation of spherical particles having

a density ρ in a medium of density ρ0 and a viscosity η0 is given
by Stokes’ law

v = [2r2(ρ - ρ0)g] / 9η0 Electroosmosis

 Opposite in principle to electrophoresis
VISCOSITY
 Liquid moves through a plug or a membrane across which a
potential is applied
 Expression of resistance to flow of a system under an applied
 Finding for the Zeta potential
stress
 More viscous = greater force is applied to make it flow at a Sedimentation Potential
particular rate
 Reverse of electrophoresis
 Creation of potential when particles undergo sedimentation
ELECTRIC PROPERTIES
Streaming Potential
Nernst Potential
 Differs from electroosmosis
 Also known as electrothermodynamic potential
 Forcing a liquid to flow through a plug or bed of particles which
 Difference in potential between the actual surface of the particle
creates the potential
and the electroneutral region of the dispersion

Renhart M. Salas, fRPh 3|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 5: Heterogenous Systems
Lecturer: Mairre Louie D. Punsalan
PHARMACEUTICAL APPLICATIONS OF COLLOIDS
 Hydrogels
 Microparticles
 Emulsions / Microemulsions
 Liposomes
 Micelles
 Nanoparticles
 Nanocrystals
COARSE DISPERSIONS
Suspensions
 Insoluble solid particles are dispersed in a liquid medium
 Particles have diameters for the most part greater than 0.1um
 Some of the particles can be observed under microscope 
exhibits Brownian motion
 Examples
 Oral antibiotic formulations
 Antacids and radiopaque suspensions
 Parenteral suspensions – must not have 0.5-30%
solid particles
 Acceptable qualities
 Suspended material should not settle rapidly
 Particles settling at the bottom of container may be
readily redispersed (not hard cake) when shaken
 Must not be too viscous  flow freely
Important Considerations
 Physical stability of suspensions – condition in which the
particles do not aggregate and in which they remain uniformly
distributed throughout the dispersion (or readily redispersed)
 Thermodynamically unstable – particles are highly energetic
and tend to regroup in such a way as to decrease the total area
and reduce surface free energy (we do not want instability)
 Reduce the solid to small particles  dispersed
 Large surface area will result to comminution,
making the system thermodynamically unstable
 Flocculate – light, fluffy conglomerates that are held together
by weak van der Waals forces (good suspension)
 Flocculates will settle rapidly, but can easily be
redispersed (and not form cake) due to the weak
bonds
 Deflocculated – does not use flocculates, settle
slowly (which is good), but slow settling will form
sediments  aggregation will occur  hard cake
 Aggregates – particles that adhere to stronger forces
Settling in Suspensions
 Theory of Sedimentation – Stoke’s Law
 Effect of Brownian Movement
 Brownian movement counteracts sedimentation to
measurable extent at room temperature by keeping
the dispersed material in random motion
Formulation of Suspensions
 Use of structured vehicle – maintain deflocculated particles
 Application of principles of flocculation – NO CAKING
EMULSIONS
 Dispersed system consisting of at least two immiscible liquid
phases, one of which is dispersed as globules in another liquid
phase  unstable systems
 Dispersed Liquid / Phase – Internal Phase (discontinuous)
 Dispersion Vehicle / Phase – External Phase (continuous)
 Third Phase – emulsifier  stabilizes emulsions
Types of Emulsions
 Oil-in-Water Emulsion (O/W)
 When an oil phase is dispersed into water
 Internal phase – oil
 External phase – water
 Water-in-Oil Emulsion (W/O)
 When the water phase is dispersed into oil
 Internal phase – water
 External phase – oil
Preparation of Emulsions
 In preparation of emulsions, a third phase should be use. This
third phase is known as emulsifier.
 Emulsifiers can interact with both oil and water phases, having
affinity with both oil and water.
 Emulsifiers are usually surfactants, which are surface-active
agents.
Surface Active Agents
 Also known as surfactants
 Used in preparation of emulsions in reducing the interfacial
tension between two immiscible liquids or particles and a
vehicle
Theories of Emulsification
 Surface Tension Theory – makes use of emulsifiers and
stabilizers to lower down interfacial tension, especially of two
immiscible liquids  reduce repellent force between the liquids
 diminish attraction and break up globules into smaller ones
 lesser tendency to reunite or coalescence
 Oriented-Wedge Theory – a monomolecular layer of
emulsifying agent is curved around a droplet of the internal
phase of an emulsion; depending on the size, shape, solubility
characteristics, and orientation of the molecules, the wedge
shape is envisioned for the molecules to either oil or water
globules to be surrounded
 Interfacial Film Theory – thin film of emulsifying agent at the
interface, in between droplets and on their surface; tough and
pliable film is to prevent contact of the dispersed phase and
dispersion vehicle
Advantages of Emulsions
 Enhanced solubility – especially for water-insoluble drugs
 Suitability for consumption – oily solutions may not be
appropriate to directly consume
 Improved palatability
 Enhanced drug absorption
Instability in Emulsions
 Flocculation – aggregation, conglomerates of small aggregates
 Simple shaking can redisperse floccules
 Coalescence – dispersed phase come together  large droplets
 Cannot be redispersed anymore into smaller ones
 Phase Inversion – reversal of phase, may be due to usage of
large amount of internal phase and/or misuse of emulsifier
Renhart M. Salas, fRPh 4|Pa ge
 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 5: Heterogenous Systems
Lecturer: Mairre Louie D. Punsalan

 Creaming – upward movement of the internal phase Interfacial Tension

 Sedimentation – downward movement of the internal phase  Force per unit length existing at
 Breaking – separation of internal and external phase, may be the interface between two
due to incorrect use of emulsifier immiscible liquid phases
 Caking – kapag nagbuo ‘yung emulsion  Similar in the case of emulsions

Phenomenon Interface Unit

Surface tension L-G, S-G dyne/cm, N/m
Interfacial tension S-S, L-L, S-L dyne/cm

MEASUREMENT OF TENSION

Capillary Rise Method

SEMISOLIDS
 Gels – solid or semisolid system of at least two (2) constituents
consisting of a condensed mass enclosing and interpenetrated
by a liquid
 Jelly – when the coherent matrix is liquid
 Xerogel – when the liquid is removed and only the
framework remains (e.g., gelatin sheets, tragacanth)
 Liquid generally rises the capillary
tube a certain distance
 The capillary tube can be placed in a
liquid contained in a beaker  liquid
will rise
 Force between the liquid molecules
and capillary wall, which is greater
than those two molecules
 For surface tension of liquid
DuNouy Tensiometer
 Depends on the fact that the force
necessary to detach a platinum-
iridium ring immersed at the surface
or interface is proportional to the
surface or interfacial tension
 The wire provides the amount of
force needed to detach the ring in
dynes on a calibrated dial

SURFACE-ACTIVE AGENTS

 Also known as surfactant

 Alternative: amphiphile (amphiphilic or amphipathic)
 Amphiphilic nature that causes surfactants to be adsorbed at
interfaces – L-G, L-L
 Affinity for both polar and nonpolar solvents
 Syneresis – gel structure shrinks due to pressing out of liquid  Have both hydrophilic and lipophilic properties
(e.g., gelatin desserts), sometimes through time
 Bleeding – liberation of liquid from the base  deficient gel A scale showing surfactant function
structure rather than the contraction involved in syneresis on the basis of hydrophilic-
lipophilic balance (HLB) values.
 Swelling – opposite of syneresis, takes up liquid, hence, volume
is increased
HLB – values on the basis of the
 Imbibition – takes an amount of liquid, but in comparison to
surfactant function (higher value –
swelling, it does not take an appreciable amount of volume
hydrophilic; low value – lipophilic)
INTERFACIAL PHENOMENA
LIQUID INTERFACES

In the liquid state, the cohesive forces between adjacent molecules are well-
developed.

Surface Tension
 A force pulls the molecules of the HLB Values
interface together and contracts the Utilities HLB Value Examples
surface Antifoaming agent 1-3 Mineral oil, fatty alcohol, wax
W/O emulsifying agent 4-6 Span 80, lanolin
 Force per unit length that must be
Wetting agent 7-9 Brij 30, docusate sodium
applied parallel to the surface to O/W emulsifying agent 8-18 Tween 20, Cremophor A25
counterbalance the net inward pull Detergent 13-15 Alkyl benzene sulfonates
Solubilizing agent 15-20 Sodium lauryl sulfate

Renhart M. Salas, fRPh 5|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 5: Heterogenous Systems
Lecturer: Mairre Louie D. Punsalan

Type Description Examples

Long chain molecules of
Sodium lauryl sulfate
Anionic carboxylates, sulfates, or
(solubilizer in surfactants)
sulfonates
Interactions with negatively
charged surfaces such as cell
Cationic Benzalkonium chloride
membranes; cytotoxic; used as
antimicrobial preservatives
Most of the naturally occurring Polypeptides, proteins,
Amphoteric surfactants in the biological alkyl betaines, lecithins,
system; are zwitterions cephalin
Fatty alcohols, steroid
Long but contain a small alcohol
alcohols, cholesterol,
base such as propylene glycol,
polyoxyethylene glyceryl
Nonionic sorbitan, or glycerol to which
esters, polyoxypropylene
fatty acids are attached to form
esters, polyoxyethylene-
the fatty acid esters
stearyl ether

Wetting Phenomena
 Wetting is the process known to be the adsorption of pure liquid
by solid particle resulting in the formation of a liquid film over
the particle surface
 Chemically, non-wetting may be due to failure of the liquid to
displace the film of air and/or other substances at the particle
surface (sometimes due to repellents)

Wetting Agent
 A wetting agent is a surfactant that, when dissolved in water,
lowers the advancing contact angle (dictates if it is possible to
have wetting), aids in displacing an air phase at the surface, and
replaces it with a liquid phase
 Examples:
 Dispersion of powders in liquid vehicles
 Displacement of air from matrix of cotton pads
 Displacement of dirt using detergents
 Application of medicinal lotions

Contact Angle
 The most important action of a wetting agent is to lower the
contact angle between the surface and the wetting liquid
 The lower the contact angle, the better wetting capacity
 The contact angle is the angle between a liquid droplet and the
surface over which it spreads
 Rule: ↑θ, ↓ wetting
 The wetting tendency is larger, the smaller the contact angle or
the surface tension is
 A wetting liquid is a liquid that forms a contact angle with the
solid which is smaller than 90º (0° - wetting)
 A non-wetting liquid creates a contact angle between 90º and
180º with the solid (180° - completely non-wetting)

Renhart M. Salas, fRPh 6|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 6: Rheology
Lecturer: Mairre Louie D. Punsalan

OUTLINE VISCOSITY
Rheology
Newtonian Systems  Expression of the resistance of a fluid to flow
Non-Newtonian Systems  The higher the viscosity, the greater is the resistance
Thixotropy  Unit: poise
Determination of Rheologic Properties
n = F / G where
OBJECTIVES
 Define rheology and provide examples of fluid  Shearing stress (F) – amount of fore per unit area required to
pharmaceutical products exhibiting various rheologic cause a liquid to flow; expressed in dyne/cm2
behaviors, and describe the application of rheology in the  Rate of shear (G) – velocity of the system that leads to the
pharmaceutical sciences and practice of pharmacy deformation of liquid; expressed in revolutions per minute
 Understand various concepts involving rheology (rev/min)
 Define and understand flow properties, Newton’s law of flow
and its application Fluidity
 Reciprocal of viscosity: ø = 1 / n
RHEOLOGY  Absolute viscosity – internal friction; resistance of fluid to flow
 Unit: centipoise, poise
 Greek words  Shearing stress divided by rate of shear
 “rheo” – to flow  Kinematic viscosity – absolute viscosity to density
 “logos” – science  Unit: centistoke, stoke
 Science of flow and deformation of matter  Absolute viscosity divided by density
 Describe the flow of liquids and deformation of solids  Relative viscosity – absolute viscosity of liquid to water
 Viscosity – resistance to flow (unitless)

Fundamentals of Rheology Kinematic Viscosity

 Industrial application  Absolute viscosity divided by the density of the liquid at a
 Paints, inks, doughs, road-building materials, specified temperature
cosmetics, dairy products, and other materials
 Pharmaceutical industry Kinematic viscosity = n / p
 Formulation and analysis of products
 Emulsions, pastes, suppositories – acceptable Example
consistency and produced with the same product An Ostwald viscometer was used to measure acetone, which was found to
properties have a viscosity of 0.313cp at 25℃. Its density at 25℃ is 0.788g/cm3. What
is the kinematic viscosity of acetone at 25℃?
NEWTONIAN SYSTEMS
Kinematic viscosity = n / p
 Each lower layer will move with a velocity directly proportional Kinematic viscosity = 0.313cp / 0.788g/cm3
to its distance from stationary bottom layer Kinematic viscosity = 0.3972 centistoke
 Direct relationship between shearing stress and rate of shear 
increasing shearing stress, increasing rate of shear NON-NEWTONIAN SYSTEMS
 Constant viscosity with increasing rate (linear)
 Examples: water, ethanol, acetone, glycerine, benzene, and  Major of products are not simple liquids  more studied
most solvents  Liquid and solid heterogenous dispersions such as colloids,
emulsions, ointments, liquid suspensions, and others
Newtonian flow
 X axis – shearing stress Plastic Flow
 Y axis – rate of shear  Also known as Bingham bodies
 Curves do not pass through the origin but rather intersect the
shearing stress axis at a particular point referred to as the yield
value
 Does not begin to flow until a shearing stress corresponding to
the yield value is exceeded
 Examples: flocculated suspensions, gels, ointments, pastes, and
Newton’s Law of Flow creams such as toothpaste
 First to study flow properties of liquids in a quantitative way
 High viscosity, greater force per unit area, high shearing stress U=
F−f
where
G

Block of liquid which may consist of parallel  U – plastic viscosity

plates  like a deck of card  F – shearing stress
 f – yield value
If the bottom layer is fixed in place and the  G – rate of shear
top is being moved at a constant velocity (F),
each lower layer can move with a velocity
directly proportional to its distance from the
stationary, bottom layer

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 6: Rheology
Lecturer: Mairre Louie D. Punsalan

Example  Rare property of a non-Newtonian fluid; time-dependent with

A plastic material was found to have a yield value of 5200 dynes/cm2. At
shearing stresses above the yield value, F was found to increase linearly
with G. If the rate of shear was 150sec−1 when F was 8000 dynes/cm2,
calculate U, the plastic viscosity of the sample.
U = (F – f) / G
U = (8000 dynes/cm2 – 5200 dynes/cm2) / 150sec-1 Application of Thixotropy
U = 18.6667 poise
Pseudoplastic Flow
 Also known as shear-thinning systems
 Consistency curve for a pseudoplastic material begins at the
origin; no yield value
 Viscosity decreases with increasing rate of shear
 Examples: dispersion of gums (tragacanth, sodium alginate,
carboxymethylcellulose [CMC], methylcellulose), paints,
ketchup
increasing viscosity  the longer the fluid undergoes a force,
the higher its viscosity
 Sol-gel transformation
 Examples: printer ink, gypsum paste, synovial fluid, serum
albumin, and hyaluronate
 Thixotropy is a very desirable property in liquid pharmaceutical
systems  high consistency, pour/spread easily
 A well-formulated thixotropy such as a suspension  will not
settle out readily , will become fluid upon shaking, regain
consistency
 Stability
 Sedimentation: higher thixotropy, lesser settling
 Parenteral formulations
 High inherent thixotropy, shear-thinning  easier
flow of the drug when injected

DETERMINATION OF RHEOLOGIC PROPERTIES

Measurements
 Capillary Tube Viscometers
 Measure the time required for a given volume of
liquid to flow through a capillary
 Examples
 Ostwald Viscometer
Dilatant Flow  Ubbelohde Viscometer
 Also known as shear-thickening systems
 Increase in resistance to flow with increasing rates of shear
 Inverse of pseudoplastic flow
 Viscosity increases with increasing rate of shear
 Examples: zinc oxide (ZnO), barium sulfate (BaSO4), titanium
dioxide (TiO2), cornstarch in water, whipped cream, ink
(particularly cartridge-based)

Ostwald Viscometer Ubbelohde Viscometer

Poiseuille’s Law
 Most useful method; for capillary tube viscometers
 Usually used to determine relative or specific viscosity rather
than absolute viscosity

8nl(V/t) 1/4
r=( ) where
THIXOTROPY π△P

Similar to some non-Newtonian systems, except that they are time-  r – radius of the capillary
dependent  time related to thixotropy and rheopexy  n – viscosity
 l – length of capillary
 V – volume
 An isothermal and comparatively slow recovery, on standing of
 t – time of flow
a material, of a consistency lost through shearing
 π – 3.14 (value to be used all throughout)
 Time-dependent, shear-thinning property
 △P – pressure drop; pressure head in which the liquid flows;
 Thixotropy can be applied only to shear-thinning systems
dynes/cm2
 Resembles gel-sol transformation
n = (πr4t△P) / (8lV)
Negative Thixotropy
 Antithixotropy; represents an increase rather than a decrease in Example
consistency on the down-curve Calculate the radius of an artery if the viscosity of blood at normal body
 Increase in thickness or resistance to flow with increased time temperature is 0.04 dyne sec/cm2, with distances of 1cm along it. The
of shear average rate of blood flow (V/t), at rest, is 80cm3/sec, and the pressure drop,
 Example: magnesia magma ΔP, is 3.8mmHg.
 Use: 1 dyne/cm2 = 7.5x10-4mmHg
Rheopexy
 A solid forms a gel more readily when gently shaken or △P = 3.8 mmHg  3.8mmHg / 7.5x10-4 mmHg = 5066.6667 dyne/cm2
otherwise sheared than when allowed to form the gel while the (8)(0.04 dyne sec/cm2)(1cm)(80cm3/sec) 1/4
r=[ ]
material is kept at rest (3.14)(5066.6667 dyne/cm2)
r = 0.2003cm

Renhart M. Salas, fRPh 2|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 6: Rheology
Lecturer: Mairre Louie D. Punsalan

Falling-Sphere Viscometers
 Glass or steel ball rolls down an almost vertical glass tube
containing the test liquid at a known constant temperature
 The rate at which a ball of a particular density and diameter falls
is an inverse function of the viscosity of the sample

Cup-and-Bob Viscometers
 Sample is sheared in the space between the outer wall of a bob
and the inner wall of a cup into which the bob fits
 Make use of a bob or spindle which is immersed in the liquid
whose viscosity is to be determined

Drive shaft

Torque set proportional to shearing

stress in sample (loop-like)

Stationary cup (outer container)

Bob (container surrounded by sample;

spindle)

Sample undergoing shear (pink)

Bubble of entrapped air (middle box)

 Rotating bob (Searle type)

 Brookfield Synchro-Lectric
 Rotovisco
 Stormer
 Rotating cup (Couette type)
 MacMichael
 Coaxial-cylinder

Cone-and-Plate Viscometers
 The sample is placed at the center of the plate, which is then
raised into position under the cone
 There is a variable speed motor, sample is being shared
(rev/min)  compare to a certain reading or scale
 Example: Ferranti-Shirley viscometer

Cone

Plate

Renhart M. Salas, fRPh 3|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 7: Micromeritics
Lecturer: Mairre Louie D. Punsalan

OUTLINE SIEVING
Fundamental Properties of Particles
Methods of Determining Particle Size  This method uses a series of standard sieves calibrated by the
Derived Properties of Powder National Bureau of Standards
 Sieves are generally used for grading coarser particles
OBJECTIVES  Involves size classification followed by the determination of the
 Understand the concept of particle size as it applies to the weight of each fraction
pharmaceutical sciences
 Discuss the common particle sizes of pharmaceutical Sieve/Mesh Number
preparations and their impact on pharmaceutical  Number of opening per linear inch
processing/preparation  Higher number, greater fineness
 Describe the different methods of determining particle size,  20, 40, 60, 80, 100, 120
surface area, bulk density, angle of repose, compressibility,
and porosity of particles
Description Sieve Opening (um)
FUNDAMENTAL PROPERTIES OF PARTICLES Coarse 355-1000
Moderately fine 180-355
Micromeritics Fine 125-180
Very fine <125
 Defined as the science and technology of small particles
 Study of small properties  solid dosage forms, powders
SEDIMENTATION
Description Particle Size (um) Use
Granulation 1000-3360 Tablet preparation  Measured using Andreasen apparatus
Coarse powder 150-1000 Drug powders  Employs the settling of particles in a liquid of a
Fine powder 50-100 Drug powders relatively low density under the influence of a
Emulsion & suspension 10-50
Coarse emulsions and gravitational or centrifugal field
flocculated suspensions  Sedimentation rate is directly proportional to the
Dry powder 1-5 Inhalation particle size; follows Stoke’s Law
Nanoemulsion 0.01-0.5 Colloids
Nanoparticle 0.001-0.1 Novel drug delivery system
PARTICLE VOLUME MEASUREMENT
Description Particle Size Range
Coarse powder >1000um or 1mm  Coulter Counter
Conventional 50-100um  HIAC/Royco Instrument
Fine particle 1-50um  Gelman Counter
Very fine 0.1-1um
Ultrafine <0.1um COULTER COUNTER

METHODS FOR DETERMINING PARTICLE SIZE  When a particle suspended in a

OPTICAL MICROSCOPY conducting liquid passes through a
small orifice on either side of which
 It should be possible to use the ordinary microscope for are electrodes, a change in electric
particle-size measurement in the range of 0.2-100um resistance occurs
 Advantage: individual particles can be seen  Count the voltage pulses and also
 Disadvantage: only two-dimensional images can be seen; no involves the blockade or blocking of
estimation of depth (thickness) electrodes

Type Description HIAC/ROYCO INSTRUMENT

Measure of the distance between tangent (intersecting
Feret diameter
the circle once) parallel to some fixed direction
Diameter of a circle with the same area as that of the
Projected area
particle observed perpendicular to the surface on
diameter
which the particle rest
Martin diameter Taken as the length of a line that bisects the particle
 More used, most cost-effective
 Involves a light blockade
 Use a laser light source for light
obscuration sensors
 Light obscuration allows for a quick
and easy particle counting and
sizing in seconds
 Fully automated method  minimal
human error
 Light obscuration is an analytical technique to which individual
particles in the liquid suspension are being placed between a
laser light source and a detector
 Measured by the detector, which will also process
the signal and give the quantification of particles
determining its size
 Laser light – illuminates the individual particles,
resulting in the shadow or blockage of light
 Obscuration – shadow or blockade

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 7: Micromeritics
Lecturer: Mairre Louie D. Punsalan

DERIVED PROPERTIES OF POWDERS Hausner Ratio

 It is a number that is correlated to the flowability of a powder
Void Volume or granular material
 Void volume (v) – volume of the spaces  Increase in Hausner ratio, decrease in flowability
 Bulk volume (Vb) – volume occupied
 Total volume of the material measured HR = TD/BD
with a graduated cylinder HR = BV/TV
 For every bulk volume, there is a void
volume Compressibility / Carr’s Index
 True volume (Vp) – true volume of particles (does  It is a measure of the relative volume change of a fluid or solid
not contain internal pores) as a response to a pressure (or mean stress) change
 Increase in Carr’s index, decrease in flowability
v = V b - Vp  Indication of compressibility
 Named after scientist Ralph J. Carr, Jr.
If the powder is considered nonporous where there is no internal pores or
capillary spaces, the bulk volume of the powder will then consist of the true CI = [(TD-BD) / TD] x 100
volume of the solid plus the volume of the spaces between the particles  CI = [(BV-TV) / BV] x 100
actual volume, regardless (or outside/without) of the internal force or
capillary spaces Compressibility Index (%) Flow Character Hausner Ratio
<10 Excellent 1.00-1.11
Porosity or Voids (ƹ) 11-15 Good 1.12-1.18
 Ratio of the void volume to the bulk volume 16-20 Fair 1.19-1.25
 Measure of the void volume in a powder material 21-25 Passable 1.26-1.34
expressed as a fraction or percentage of the total 26-31 Poor 1.35-1.45
volume 32-37 Very poor 1.46-1.59
 Porosity is frequently expressed in percent, ƹ x 100 >38 Very, very poor >1.60
 Expressed as 0-1 or as percentage, 0-100
Example
ƹ = (Vb–Vp) / Vb = 1 – (Vp/Vb) = (v/Vb) x 100 A powder was poured into a graduated cylinder and was noted to have a
volume of 65mL. It was allowed to compressed by pounding the cylinder
Example on the table top. The final volume was reduced by 15mL. Determine the
A sample of calcium oxide powder with a true density of 3.203g/cm3 and compressibility index and Hausner ratio of the powder.
weighing 131.3g was found to have a bulk volume of 82.0cm3 when placed
in a 100mL graduated cylinder. Calculate the porosity. HR = BV / TV
 TV = 65mL – 15mL = 50mL
Vp = mass / true density HR = 65mL / 50mL
Vp = 131.3g / 3.203g/cm3 HR = 1.3 (passable)
Vp = 41cm3
CI = [(BV-TV) / BV] x 100
ƹ = [(Vb–Vp) / Vb] x 100 CI = [(65mL – 50mL) / 65mL] x 100
ƹ = [(82cm3 – 41cm3) / 82cm3] x 100 CI = 23.0769% passable
ƹ = 0.5 or 50%
Angle of Repose
DENSITIES OF PARTICLES  Measures the angle of pile of material at rest and give some
recognition of a powder’s ability to flow
 True density – density of the actual solid material (mass/vol)  The powder flows through a funnel and falls freely on a surface
 Bulk density – mass of a powder divided by the bulk volume
 Tapped density – refers to the bulk density of the powder after Ө = arc tan (h/r)
a specified compaction process, usually involving vibration of Ө = arc tan (2h/d)
the container
Angle of Repose Interpretation
25-30 Excellent
Bulkiness
31-35 Good
 Specific bulk volume, the reciprocal of bulk density, is often 36-40 Fair
called bulkiness or bulk 41-45 Passable
 It is an important consideration in the packaging of powders 46-55 Poor
 Bulkiness increases with a decrease in particle size 56-65 Very poor
 In a mixture of materials of different sizes, however, the smaller >65 Very, very poor
particles shift between the larger ones and tend to reduce the
bulkiness Examples
A 100g powder was dropped from a funnel suspended at a height of 20cm
FLOW PROPERTIES made an elevation of 12mm from the surface. The powder was noted to
have made a spread of 5cm. Determine the angle of repose.
 Powder flowability – defined as the ease with which a powder
will flow under a set of conditions Ө = arc tan (2h/d)
 Methods of evaluating flow properties  h = 12mm  1.2cm
 Carr’s Index (Compressibility) Ө = arc tan [2(1.2cm) / 5cm]
 Hausner Ratio Ө = arc tan (2.4cm / 5cm)
 Angle of Ratio Ө = 25.6410° excellent

Renhart M. Salas, fRPh 2|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LECTURE)
Module 7: Micromeritics
Lecturer: Mairre Louie D. Punsalan

A powder was known to produce an angle of 30º with a spread of 40cm.

What would be the expected height of the funnel?

Ө = arc tan (2h/d)  tanӨ = 2h/d

2h = (tanӨ)(d)  h = dtanӨ / 2
h = 40tan30° / 2
h = 11.5470cm

Renhart M. Salas, fRPh 3|Pa ge