UNIT 01/PART 01: BP 403T_PHYSICAL PHARMACEUTICS: INTRODUCTION

Date: 10 – 04 – 2021
Shailender Mohan, Assistant Professor, HIP, Lucknow
Bachelor of Pharmacy
(2nd Year - IV Semester)
BP 403T: Physical Pharmaceutics – II
(Theory)
HARSHA INSTITUTE OF PHARMACY

Date: 10 – 04 – 2021

Within the field of pharmacy, the colloidal systems we commonly come across
include some protein and polymer solutions, micellar systems, liquid
crystals and emulsions, suspensions, aerosols, foams and other drug
delivery systems that fall within the colloidal size range.
In some instances, what was formally referred to as colloidal systems have been replaced by
the term nanotechnology (structures that have one or more dimension between approximately
1 and 100 nm).
UNIT 01: Colloidal Dispersion
Date: 10 – 04 – 2021

Date: 10 – 04 – 2021
Colloidal dispersions consist of at least two phases: one or more dispersed or internal
phases, and a continuous or external phase called the dispersion medium or vehicle.
Colloidal dispersions are distinguished from solutions and coarse dispersions by the particle
size of the dispersed phase, not its composition.
Colloidal dispersions can be characterized as containing particles in the size range of
between approximately 1 nm and 1 micrometer, however a smaller size range of up to 500
nm is also quoted.
Thus, blood, cell membranes, micelles, thinner nerve fibers, milk, rubber latex, fog, and beer
foam are colloidal systems. Some materials, such as emulsions and suspensions of most organic
drugs, are coarser than true colloidal systems but exhibit similar behavior.

Date: 10 – 04 – 2021
SHAPE OF COLLOIDAL PARTICLES
The shape adopted by colloidal particles in dispersion is important because the more extended
the particle, the greater is its specific surface and the greater is the opportunity for attractive
forces to develop between the particles of the dispersed phase and the dispersion medium.
An appreciable fraction of atoms, ions, or molecules of colloidal particles are located in the
boundary layer between the particle and the dispersion medium.
The boundary layer between a particle and air is commonly referred to as a surface, whereas
the boundary layer between a particle and a liquid or solid is commonly referred to as an
interface.

Date: 10 – 04 – 2021
The ions or molecules within the particle and within the medium are surrounded on all sides by
similar ions or molecules and have balanced force fields; however, the ions or molecules at
surfaces or interfaces are subjected to unbalanced forces of attraction.
Consequently, a surface free-energy component is added to the total free energy of colloidal
particles and becomes important as the particles become smaller and a greater fraction of their
atoms, ions, or molecules are located in the surface or interfacial region.
As a result, the solubility of very fine solid particles and the vapor pressure of very small
liquid droplets are greater than the corresponding values for coarse particles and drops
of the same materials.

Date: 10 – 04 – 2021
Specific Surface Area
Decreasing particle size increases the surface-to-volume ratio, expressed as the specific
surface area (Asp). Specific surface area can expressed as the area (A, cm2) per unit volume
(V, cm3) or per unit mass (M, grams).
For a sphere, A = 4πr2 and V = 4/3πr3, then Asp is:

Date: 10 – 04 – 2021
The shapes that can be assumed by colloidal particles are: (a) spheres and globules, (b) short
rods and prolate ellipsoids (rugby ball-shaped/elongated), (c) oblate ellipsoids (discus-
shaped/flattened) and flakes, (d) long rods and threads, (e) loosely coiled threads, and (f)
branched threads.
The following properties are affected by changes in the shape of colloidal particles:
a) Flowability b) Sedimentation
c) Osmotic pressure d) Pharmacological action.

Date: 10 – 04 – 2021
PHYSICAL STATES OF DISPERSED AND CONTINUOUS PHASES
A useful classification of colloidal systems is based upon the state of matter of the dispersed
phase and the dispersion medium (i.e., whether they are solid, liquid, or gaseous).
NOTE:
The terms sols and gels are often applied to colloidal dispersions of a solid in a liquid or gaseous medium.
Sols tend to have a lower viscosity and are fluid. If the solid particles form bridged structures possessing some
mechanical strength, the system is then called a gel.
For example, hydrosol (or hydrogel), alcosol (or alcogel), and aerosol (or aerogel) designate water, alcohol, and
air, respectively.

Date: 10 – 04 – 2021
Source: Ramington’s Essentials for Pharmaceutics.

Date: 10 – 04 – 2021
INTERACTION BETWEEN DISPERSED PHASES AND DISPERSION MEDIUMS
Ostwald originated another useful classification of colloidal dispersions based on the affinity
or interaction between the dispersed phase and the dispersion medium.*
*This classification refers mostly to solid-in-liquid dispersions.
Colloidal dispersions are divided into the two broad categories, lyophilic and lyophobic.
Some soluble, low-molecular-weight substances have molecules with both tendencies and
associate in solution, forming a third category called association colloids.

Date: 10 – 04 – 2021
Lyophilic Dispersions
• The system is said to be lyophilic (solvent-loving) if there is considerable attraction
between the dispersed phase and the liquid vehicle (i.e., extensive solvation).
• The system is said to be hydrophilic if the dispersion medium is water. Due to the presence of high
concentrations of hydrophilic groups, solids such as bentonite, starch, gelatin, acacia, and povidone swell,
disperse, or dissolve spontaneously in water to the greatest degree possible without breaking covalent bonds.
• Hydrophilic colloids often contain ionized groups that dissociate into highly hydrated ions
(e.g., carboxylate, sulfonate, and alkylammonium ions) and/or organic functional groups
that bind water through hydrogen bonding (e.g., hydroxyl, carbonyl, amino, and imino
groups).

Date: 10 – 04 – 2021
Hydrophilic colloidal dispersions can be further subdivided as:
True solutions: water-soluble polymers (e.g., acacia and povidone)
Gelled solutions, gels, or jellies: polymers present at sufficiently high concentrations and/or
at temperatures where their water solubility is low, such as relatively concentrated solutions
of gelatin and starch (which set to gels upon cooling) and methylcellulose (which gels upon
heating).
Particulate dispersions: solids that do not form molecular solutions but remain as discrete
though minute particles (e.g., bentonite and microcrystalline cellulose) Lipophilic or
oleophilic substances have a strong affinity for oils.

Date: 10 – 04 – 2021
Oils are non-polar liquids consisting mainly of hydrocarbons having few polar groups and low
dielectric constants.
Examples include mineral oil, benzene, carbon tetrachloride, vegetable oils (e.g.,
cottonseed or peanut oil), and essential oils (e.g., lemon or peppermint oil).
Oleophilic colloidal dispersions include polymers such as polystyrene and un-vulcanized or
gum rubber dissolved in benzene, magnesium, or aluminum stearate dissolved or dispersed in
cottonseed oil, and activated charcoal, which forms sols or particulate dispersions in all oils.

Date: 10 – 04 – 2021
Lyophobic Dispersions
The dispersion is said to be lyophobic (solvent-hating) when there is little attraction between
the dispersed phase and the dispersion medium.
Hydrophobic dispersions consist of particles that are only hydrated slightly or not at all,
because water molecules prefer to interact with one another instead of solvating the particles.
Therefore, such particles do not disperse or dissolve spontaneously in water.

Date: 10 – 04 – 2021
Examples of materials that form Hydrophobic Dispersions include organic compounds
consisting largely of hydrocarbon portions with few;
Hydrophilic functional groups (e.g., cholesterol and other steroids);
some Non-ionized Inorganic substances (e.g., sulfur); and
Oleophilic materials such as polystyrene or gum rubber, organic lipophilic drugs, paraffin
wax, magnesium stearate, and cottonseed or soybean oils.

Date: 10 – 04 – 2021
Association Colloids
Organic compounds that contain large hydrophobic moieties on the same molecule with
strongly hydrophilic groups are said to be amphiphilic.
The individual molecules are generally too small to be in the colloidal size range, but they tend
to associate into larger aggregates when dissolved in water or oil.
These compounds are designated association colloids, because their aggregates are large
enough to qualify as colloidal particles.
Examples include surfactant molecules that associate into micelles above their critical micelle
concentration (CMC) and phospholipids that associate into cellular membranes and
liposomes, which have been used for drug delivery.

Date: 10 – 04 – 2021
PROPERTIES OF COLLOIDAL DISPERSIONS
Particle shape:
Particle shape depends upon the chemical and physical nature of the dispersed phase and the
method employed to prepare the dispersion.
Primary particles exist in a wide variety of shapes, and their aggregation produces an even
wider variety of shapes and structures.

Date: 10 – 04 – 2021
DIFFUSION AND SEDIMENTATION
The molecules of a gas or liquid are engaged in a perpetual and random thermal motion causing
collisions with one another and with the container wall billions of times per second.
Each collision changes the direction and the velocity of these molecules.
The continuous motion of molecules of a dispersion medium randomly buffets any dissolved
molecules and suspended colloidal particles.
The random bombardment imparts an erratic movement called brownian motion to
solutes and particles.

Date: 10 – 04 – 2021
The brownian motion of colloidal particles magnifies the random movements of molecules in
the liquid or gaseous suspending medium and represents a three-dimensional random walk.
Suspended colloidal particles and solute molecules undergo both rotational and
translational brownian movements.
For translational motion, Einstein derived the equation:

Date: 10 – 04 – 2021
Brownian motion and convection currents maintain dissolved molecules and small colloidal
particles in suspension indefinitely.
This is true for all intrinsically stable systems when dissolution or dispersion occurs
spontaneously and the corresponding free energy change is negative.
*In meta-stable or diuturna (i.e., durable, lasting) dispersions, brownian motion prevents sedimentation and may
extend their life for years.

Date: 10 – 04 – 2021
As particle size or r increases, brownian motion decreases as seen by the x¯ proportionality to
r−1/2.
Larger particles have a greater tendency than smaller particles of the same material to settle
to the bottom of the dispersion, provided the densities of the dispersed phase, dP, and the
liquid vehicle, dL, are sufficiently different (sedimentation, when dP > dL).
On the other hand, larger particles will rise to the top of the dispersion when dP < dL.
This is known as creaming.

Date: 10 – 04 – 2021
The Stokes equation reflects the rate of sedimentation/creaming; it is expressed as:
where h is the height (or distance) that a spherical particle moves in time t, and g is the
acceleration of gravity. The equation illustrates that this rate is proportional to r2.
Consequently, as brownian motion diminishes with increasing particle size, the tendency of
particles to sediment or cream is increased.
At a critical radius, the distance, h, that a particle settles/creams equals the mean
displacement, x, due to brownian motion over the same time interval, t, and therefore, the two
are equal.

Date: 10 – 04 – 2021
LIGHT SCATTERING
The optical properties of a medium are determined by its refractive index.
Light will pass through the medium undeflected when the refractive index is uniform
throughout.
When a narrow beam of sunlight is admitted through a small hole into a darkened room, bright
flashing points reveal the presence of the minute dust particles suspended in the air.
A beam of light striking a particle polarizes the atoms and molecules of that particle and
induces dipoles, which act as secondary sources and re-emit weak light of the same
wavelength as the incident light. This phenomenon is called light scattering.

Date: 10 – 04 – 2021
Colloidal particles suspended in a liquid also scatter light.
When an intense, narrowly defined beam of light is passed through a suspension, its path
becomes visible because of the light scattered by the particles in the beam.
This Tyndall beam is characteristic of colloidal systems and becomes most visible when
viewed against a dark background in a direction perpendicular to the incident beam.
*The magnitude of the turbidity or opalescence depends upon the nature, size, and concentration of the
dispersed particles.

Date: 10 – 04 – 2021
For example, when clear mineral oil is dispersed in an equal volume of a clear, aqueous
surfactant solution, the resultant emulsion is milky white and opaque as a result of light
scattering.
However, microemulsions containing emulsified droplets that are only about 40 nm in diameter (i.e., much smaller than the
wavelength of visible light) are transparent and clear to the naked eye.

Date: 10 – 04 – 2021
The concentration of inorganic and organic colloidal dispersions and of bacterial suspensions
can be measured by their Tyndall effect or turbidity. Turbidity, τ, is defined by an equation
analogous to Beer’s law for the absorption of light, namely:
where I0 and It are the intensities of the incident and transmitted light beams, and l is the length
of the dispersion through which the light passes.

Date: 10 – 04 – 2021
The concentration of dispersed particles can be measured in two ways using turbidity.
In turbidimetry a spectrophotometer or photoelectric colorimeter is used to measure the
intensity of the light transmitted in the incident direction.
*If the dispersion is less turbid, the intensity of light scattered at 90 degrees to the incident beam is measured with
a nephelometer.
*Both methods require careful standardization, using suspensions that contain known amounts of particles similar
to those being studied.
The turbidity of hydrophilic colloidal systems such as aqueous solutions of gums, proteins, and
other polymers is far weaker than that of lyophobic dispersions.

Date: 10 – 04 – 2021
The theory of light scattering was developed in detail by Lord Rayleigh.
For white, non-absorbing nonconductors or dielectrics like sulfur and insoluble organic
compounds, the equation obtained for spherical particles whose radius is small compared to the
wavelength of light (λ) is:
I0 is the intensity of the unpolarized incident light; Is is the intensity of light
scattered in a direction making an angle, θ, with the incident beam and
measured at a distance, d.

Date: 10 – 04 – 2021
The scattered light is largely polarized.
The concentration, c, is expressed as the number of particles per unit volume.
The refractive indices, n1 and n0, refer to the dispersion and the dispersion medium,
respectively.
Because the intensity of scattered light is inversely proportional to the fourth power of the
wavelength, blue light (λ ≈ 450 nm) is scattered much more strongly than red light (λ ≈
650 nm).

Date: 10 – 04 – 2021
Colloidal dispersions of colorless particles appear blue when the incident white light is viewed in scattered light
(i.e., in lateral directions such as 90 degrees to the incident beam).
Loss of the blue rays due to preferential scattering leaves the transmitted light yellow or red.

Date: 10 – 04 – 2021
The particles in pharmaceutical suspensions, emulsions, and lotions are generally larger than the
wavelength of light, λ.
When the particle size exceeds λ/20, destructive interference between the light scattered by
different portions of the same particle lowers the intensity of the scattered light and changes its
angular dependence

Date: 10 – 04 – 2021
Dynamic Light Scattering
Light scattered by a moving particle undergoes a Doppler shift; its frequency increases slightly
when the particle moves toward the photodetector and decreases slightly when it moves away.
This shift is so small that it can only be detected by very intense, strictly monochromatic laser
light.
Because they are engaged in random brownian motion, a set of colloidal particles scatters light
with a broadened frequency.
Smaller particles diffuse faster than larger ones and therefore produce greater Doppler
broadening. If the particles are spherical and monodisperse, and their concentration is so dilute
that they neither attract nor repel one another, the frequency broadening can be used to
estimate the particle diffusion coefficient, D.

Date: 10 – 04 – 2021
As noted above, the diffusion coefficient is inversely proportional to the particle radius. The
measured radius is actually the hydrodynamic radius (rH), which comprises the particle plus its
attached water of hydration.
The technique is called dynamic or quasi-elastic light scattering. The technique is also called
photon correlation spectroscopy (PCS), because it counts and correlates the number of
scattered photons over very short time intervals.

Date: 10 – 04 – 2021
In a related technique that uses a fiber-optic Doppler anemometer, a laser beam is carried into
the interior of a colloidal dispersion via a fiber-optic cable.
Particles in the small volume of dispersion around the immersed tip scatter light with the
Doppler frequency shift back into the same fiber to the detector.
This method is suitable for concentrated dispersions that are opaque to the laser beam and
would have to be diluted extensively for conventional dynamic light scattering measurements.

Date: 10 – 04 – 2021
VISCOSITY
Most lyophobic dispersions have viscosities only slightly greater than that of the liquid vehicle.
This holds true even at comparatively high volume fractions of the disperse phase unless the
particles form continuous network aggregates throughout the vehicle, in which case yield
stresses are observed.
By contrast, the apparent viscosities of lyophilic dispersions, especially of polymer solutions,
are several orders of magnitude greater than the viscosity of the solvent or vehicle even at
concentrations of only a few percent solids.
Lyophilic dispersions are also generally much more pseudoplastic or shear-thinning than
lyophobic dispersions.

UNIT 01/PART 01: BP 403T_PHYSICAL PHARMACEUTICS: INTRODUCTION

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UNIT 01/PART 01: BP 403T_PHYSICAL PHARMACEUTICS: INTRODUCTION