pharmaceutics ii college of (pht 312) pharmacy · •organic substance like gelatin, gum, starch,...
TRANSCRIPT
COLLEGE OF
PHARMACY
Dr. Mohammad Javed Ansari, PhD.
Contact info: [email protected]
PHARMACEUTICS II (PHT 312)
OBJECTIVES OF THE LECTURE
• At the end of this lecture, you will be aware of:
• What are disperse systems?
• What are various types of colloidal dispersion?
• What are features of colloidal dispersion?
• What are various colloidal formulations?
• How colloids are prepared?
• How colloids are purified?
• What are different properties of colloids?
• What are stability problems of colloids?
• How colloids are stabilized?
• What are pharmaceutical applications of colloids?
LECTURE OUTLINES
• Definition of Colloidal dispersion.
• Colloids in nature
• TYPES OF COLLOIDAL SYSTEMS
• Lyophilic colloids
• Lyophobic colloids
• Amphiphilic or Association Colloids
• METHOD OF PREPARATION
• Dispersion method (mill, Ultrasonic treatment)
• Condensation method: (super-saturation, chemical reaction)
• Purification / Separation of colloids.
• Ultra filtration and Dialysis, Electro-dialysis
• Properties of Colloids (Optical, Kinetic, Electrical, Electro-
kinetic).
• Stability of Colloid Systems
• Application of Colloids
•Dispersed systems consist of particulate matter known as dispersed phase, dispersed throughout a continuous or dispersion medium.
• Classified based on size of dispersed phase
•Coarse dispersion > 1 m suspension & emulsion
•Colloidal dispersion 1 nm- 1 m colloids
•Colloidal System is defined as the heterogeneous biphasic system in which dispersed phase is subdivided into nano size range (1-1000 nanometer).
•Nanoparticles are small colloidal particles, but not all small colloidal particles are nanoparticles.”
•If all particles in a colloidal system are of (nearly) the same size the system is called monodisperse; in the opposite cases the systems are heterodisperse /polydisperse.
Pharmaceutical Colloidal: Definition & Features
• It is not necessary for the units of a colloidal system to be discrete (separate particles)
• Therefore continuous network structures, the basic units of which are of colloidal dimensions also fall in this class (e.g. porous solids, gels and foams).
• Nor it is necessary for all three dimensions to be in the colloidal range.
• Films (only one dimension) and fibers (only two dimensions) are in nano range, may also be classified as colloidal.
• Eg. Hydrophillic colloids like alginates, agar gelatin, pectin, cellulose derivatives and polymers.
Pharmaceutical Colloidal: Definition & Features
Classified based upon the interaction / affinity between
dispersed colloids and dispersion medium
1. Lyophilic colloids = Solvent loving colloids.
2. Lyophobic colloids = Solvent hating colloids
3. Amphiphilic colloids = both loving colloids
• These colloids have affinity with both water as well as
Lipids therefore these are both hydrophilic and
Lipophilic.
• Based upon nature of dispersed colloids in liquids
• Liquid: colloidal emulsion
• Solid: colloidal suspension
TYPES OF COLLOIDAL DISPERSIONS
LYOPHILIC COLLOIDS: FEATURES & PREPARATION
• Have affinity with dispersion medium.
• Called as hydrophilic colloids when media is water
• Spontaneous: these colloids are spontaneously formed
by dispersing the material in the solvent.
• Organic substance like gelatin, gum, starch, egg, albumin
etc. pass readily into water to give colloidal solution.
• Stable: these colloids are very stable (don’t need any
stabilizing agents) and do not precipitate/coagulate easily.
However addition of very large quantities of electrolytes
can cause particles to precipitate.
• Reversible : If solvent is evaporated, the sol can be made
again by simply re-mixing with solvent.
•The colloidal particles have very little affinity, if any, for the
dispersion medium. Eg. In organic materiasl like Metals, their
hydroxides and sulphides.
• Don’t form spontaneously (need special techniques)
• Unstable: require stabilizing agents.
• Irreversible: once precipitated, don’t return.
A- Dispersion method: Coarse particles are reduced in size by
the use of colloidal mill or ultrasonics.
Colloidal mill: coarse material is sheared
in a narrow gap between a static cone and
a rapid rotating cone.
Ultrasonic treatment: the passage of
ultrasonic waves through a dispersion
medium.
LYOPHOBIC COLLOIDS: FEATURES & PREPARATION
B- Condensation method:
Sub-colloidal particles are caused to aggregate into
colloidal ones.
- condensation by super-saturation: high degree of initial
super-saturation followed by growth of nuclei (by change
of solvent or reduction of temperature).
e.g. addition of water to saturated alcoholic solution of
sulfur
- condensation by chemical reaction: Reduction, oxidation
or hydrolysis
e.g. oxidation of hydrogen sulfide leads to formation of
colloidal sulfur.
LYOPHOBIC COLLOIDS: FEATURES & PREPARATION
•Amphiphiles or surfactants (surface active
agents) are molecules characterized by having a
hydrophilic head and a lipophilic tail.
•When dispersed in a liquid at low concentration
the amphiphiles exist separately and are in a sub-
colloidal size range.
•When the concentration exceeds a certain level
(CMC) the molecules aggregate to form micelles
(contain 50 or more monomers).
• Micelles lie within the colloidal size range.
AMPHIPHILIC OR ASSOCIATION COLLOIDS
FEATURES & PREPARATION
Ultra filtration: Filtration using ultra filters (filters with
very small pores). Colloids can cross normal filter papers.
Dialysis / Electro-dialysis: Removal of sub colloidal
species (electrolytes / impurities) by putting the colloidal
mixture in a dialysis bag.
•An electrical potential may be used to increase the rate of
movement of ionic impurities through a dialysis membrane.
Pharmaceutical application of dialysis
Haemodialysis:
Small molecular weight impurities from
the body (blood) are removed by passage
through a membrane.
Purification / Separation of colloids
Due to their small size they do not settle out of solution.
Particles lying in the colloidal size range possess an
enormous surface area compared with the surface area of an
equal volume of larger particles.
Large specific surface area results in many unique
properties of colloidal dispersions.
Optical properties of colloids. eg. Tyndall (Faraday) Effect
Kinetic properties of colloids eg. Brownian motion,
diffusion, osmosis, viscosity etc.
Electrical Properties of Colloids eg. Zeta potential
Electro-kinetic Properties of Colloids eg. Electrophoresis
Properties of Colloids
Tyndall Effect (Light scattering Effect )
John Tyndall, a physicist observed this
phenomenon in 1869.
He observed that when a beam of light is
allowed to pass through a colloidal solution, the
path of light gets illuminated. (which was due to
scattering of light by colloidal particles).
To scatter the Light, size of the colloidal
particles must be in range within the wavelength
range of visible light i.e. 200-700 nm.
High wavelength light (Blue) is scattered more
than short wavelength light (orange & red).
Tyndall Effect (Light scattering Effect )
The intensity of the scattered light depends on
the difference between the refractive indices of the
colloidal particles and the dispersion medium.
Lyophilic colloidal particles are highly solvated,
which results into lower difference in refractive
index of two phases therefore Tyndall effect is less
pronounced in lyophilic colloids.
In case of lyophobic colloidal solution, the
difference in refractive index is quite large and
therefore it shows pronounced Tyndall effect.
Tyndall Effect (Light scattering Effect ) Light scattering measurements are of great value for
estimating particle size and shape and number of particles
per unit weight or volume.
EVALUATION OF COLLOIDS
Ultra-microscope: Allows the examination of the light
spots responsible for the Tyndall cone.
The light spots corresponding to the particles are
counted and average particle size may be calculated.
Electron Microscope: It is capable of taking pictures of
the actual particles even those approaching molecular
dimensions.
It is used to observe size, shape and structure of
colloidal particles.
• Properties which are related to the motion of particles
with respect to the dispersion medium
•1. Brownian motion
Zig zag movement of the colloidal particles.
Random collision (accident) of the colloidal particles with
the molecules of the dispersion medium.
The velocity of the particles increase with decreasing
particle size.
2. Diffusion
Particles spontaneously diffuse from a region of higher
concentration to a region of lower concentration until the
concentration of the system is uniform throughout.
2. Diffusion The rate of diffusion is expressed by Fick's first law,
= - DA
dm the amount of substance diffusing in time dt across a
plane of area A is directly proportional to concentration
gradient dc/dx (the change of concentration dc with distance
traveled dx).
D is known as the diffusion coefficient (area per unit time).
The negative sign is because diffusion occurs in the direction
of decreasing concentration.
dm dt
dc dx
Diffusion coefficient obtained from Fick's law can be
used to obtain the radius of approximately spherical
colloidal particles
D = Diffusion coefficient obtained from Fick's law
R = Molar gas constant
T = Absolute temperature
= Viscosity of the solvent
r = radius of the spherical particle
N = Avogadro's number
The diffusion coefficient may be also used to obtain the
molecular weight of approximately spherical
molecules, such as egg albumin and hemoglobin.
RT 6 r N
D =
3. Osmotic Pressure:
If a solution and a solvent are separated by a semi
permeable membrane the tendency to equalize
concentration on either side of the membrane results in a
net diffusion of solvent across the membrane.
The pressure necessary to balance the osmotic flow is
called the osmotic pressure.
Osmotic pressure can be used to determine the molecular
weight using the following equation (derived from Van’t
Hoff equation)
C = Concentration of solution T = Absolute temperature
M = Molecular weight R= Gas constant
B = Constant depending on the degree of interaction
between dispersed phase and dispersion medium
C
RT M
= + B C
4. Sedimentation The velocity v of sedimentation of spherical particles is
given by Stoke's law
v =
d = diameter of the particles
o = density of the medium
= density of the spherical colloidal particles.
g = acceleration due to gravity.
= viscosity of the medium
If the particles are only subjected to the force of gravity,
then the lower size limit of particles obeying Stoke's
equation is about 0.5 m.
d2 ( - o) g 18
This is because Brownian movement ends to counteract sedimentation due to gravity and promotes mixing.
5. Viscosity
Viscosity is an expression of the resistance to flow of
a system under an applied stress.
The more viscous a liquid, the greater the applied
force required to make it flow at a particular rate.
The present section is concerned with:
the flow properties of dilute colloidal systems
the manner in which viscosity data can be used
to obtain the molecular weight of the disperse
phase.
Viscosity studies also provide information regarding
the shape of the particles in solution.
Einstein developed an equation of flow applicable to
dilute colloidal dispersions of spherical particles:
= o (1 + 2.5 )
o = viscosity of the dispersion medium
= viscosity of the dispersion medium when the
volume fraction of colloidal particles is
The volume fraction is defined as the volume of the
particles divided by the total volume of the dispersion. Several viscosity coefficients may be defined with
respect to this equation:
relative viscosity (rel)
specific viscosity (sp)
intrinsic viscosity (int)
27 N
ove
mb
er 2
016
Relative viscosity: rel = /o = 1 + 2.5
Specific viscosity: sp= - o /o = rel -1= 2.5
Since volume fraction is directly related to concentration
sp /C = K
C = Concentration expressed in grams of colloidal
particles per 100 ml of total dispersion.
If sp/C is plotted against C and the line is extrapolated
to infinite dilution, the intercept is known as the
intrinsic viscosity int
Electrical Properties of Colloids
These are properties, which depend on, or are affected
by the presence of a charge on the surface of a colloid.
Colloids dispersed in Liquid media may become
charged mainly due to:
1. Adsorption of a particular ionic species present in
solution such as hydronium or hydroxyl ion.
Seen in most LYOPHOBIC COLLOIDS.
2. Transfer of electrons- or ions from the
substances of high dielectric constant to those of
lower one.
As a result when a colloid possesses a higher
dielectric constant than its dispersion medium, it will
acquire a positive charge and vice-versa.
Electrical Properties of Colloids
3. Ionization of functional groups of colloids (such as
COOH, SO4) as seen in most LYOPHILLIC COLLOIDS.
In these cases, the total charge is a function of pH.
(a) In alkaline solution:
The carboxylic acid groups of the protein molecules will
exist as carboxylate anions. NH2 --- R ---COO-
(b) In acid solution:
The amino groups of the molecules will be protonated:
NH3+ ---R --- COOH
At, alternative pH, known as the isoelectric point, protein
exist as zwitterion, which is electrically neutral, both
groups are ionized (Solubility of the protein will be
minimum hence precipitation will be facilitated).
Electro-kinetic phenomena Electrophoresis
•The movement of a charged colloidal particles under the
influence of an applied potential difference.
•Negatively charged colloids will move towards Anode
whereas positively charged will move towards Cathode.
•Lyophilic colloids may not show electrophoresis due to
absence of charges on colloids.
Stability of Colloid Systems
The presence and magnitude, or absence of a charge on a
colloidal particle is an important factor in the stability of
colloidal systems.
•Lyophilic & association colloids:thermodynamically stable.
•The addition of an electrolyte to a lyophilic colloid in
moderate amounts does not result in coagulation.
•Lyophobic colloids are thermodynamically unstable.
Thermodynamic stability of lyophobic colloids may be
increased by an addition of relatively small amount of
surface active substances (surfacants) lowering the interfacial
energy of the system.
Or by adding small amount of polymers to cover colloids so
that these don’t feel attractions (Steric stabilization).
Stability of Colloid Systems
The stability of hydrophobic colloids depends on the zeta
potential which is due to electrical double layer of colloids:
•when the absolute value of zeta potential is above ±30 mV
the colloidal dispersions are supposed to be stable due to
mutual repulsion (electrostatic stabilization).
•Hydrophobic colloids will aggregate and precipitate if their
electrical charge is removed / disturbed.
•Therefore addition of small amount of electrolyte or
oppositely charged colloid may lead to coagulation /
agglomeration due to decrease in the zeta potential
(repulsion index).
Application of Colloids
• Colloids are extensively used for modifying the properties of
pharmaceutical agents.
• Colloidal drugs exhibit substantially different properties when
compared with traditional forms of the dosage forms.
• The most common property that is affected is the solubility of a
drug.
• Another important pharmaceutical application of colloids is their
use as drug delivery systems.
• The most often used colloid- type delivery systems include
hydrogels, liposomes, micelles, nanoparticles, and nanoemulsions
and microemulsions.
Application of Colloids
• Hydrogels are cross-linked or interwoven polymeric
networks, which absorb and retain large amounts of water.
• Target Site specific controlled drug delivery systems.
Environment sensitive hydrogels have the ability to sense
changes in the pH, temperature, or the concentration of a
specific metabolite and release their load.
• Liposomes:lipid bilayer vesicle having aqueous cavity.
• Nanocapsules are sub-microscopic colloidal carrier systems
composed of an oily or an aqueous core surrounded by a
thin polymer membrane.
• Nanoemulsions / microemulsions are consist of very fine
oil-in-water or water in oil dispersions, having droplets
diameter smaller than 100 nm.