Good

Morning!!!
Nimfa B. Gambalan, RPh, Rchem, MSChem, PhD
 Definition
•associated with the area of pharmacy that deals
with the quantitative and theoretic principles of
science as they apply to the practice of pharmacy.
•Application of the physical and chemical
principles and laws in pharmaceutical sciences
•Application of physical chemistry in pharmacy
like in the understanding of and development of
dosage forms and drug delivery systems
 Course Outline
• Basic Principles on Measurement
• Forces of Attraction
• Gas Physical Pharmacy
• Liquid Physical Pharmacy
• Solid Physical Pharmacy
• Phase Equilibria
• Chemical Kinetics
 Dimensions and Units

3 things necessary to describe an object

1. Numerical value of the property

2. Dimensions of the property
3. Units which the value is expressed
 Fundamental Dimensions/Measurements

Dimension Symbol cgs unit SI unit

Length L cm Meter

Mass M g Kg

Time T sec sec

Temperature Θ K K
 Derived Dimensions
Derived Symbol SI unit
dimension
Area L2 m2
Volume L3 m3
Density ML-3 kg/m3
Velocity LT-1 ms-1
Acceleration LT-2 ms-2
Force MLT-2 N
 Derived Dimensions

Derived Symbol SI unit

dimension
Surface Tension MT-2

Energy ML2T-2 Joule

 Error and Describing variability
1. Determinate errors/Constant errors are those that
although some can be avoided or determined and
corrected , they are present in measurement and affect all
observations of a series in the same way
Ex. Errors inherent in a particular method used, errors in
calibration and operation of the measuring instruments,
impurities in the reagents and drugs, biased personal
errors that for example might recur consistently in reading
of a meniscus in pouring and mixing, in weighing
operations, in matching colors, etc
2. Indeterminate errors-occur by accident or
chance, and they vary from one measurement
to the next. This are errors which cannot be
allowed for or corrected because of the
natural fluctuations that occur in all
measurements.
Ex. Those that arise from random fluctuations in
temperature, humidity, pressure
 Precision and Accuracy
Presicion- is the measurement of the agreement
of data.

Accuracy- the agreement between the data and

the true value

Indeterminate errors affect precision while

determinate or constant errors affect the
accuracy of data.
Variability measures for Dispersion
1. Range- the difference between the
highestvalue and the lowest value
2. Mean deviation= ∑/Xi-Mean/ /N
3. Standard deviation
4. Variance
5. Absolute error
6. Relative error
 Atomic and Molecular
Structure

Atom
 particle of matter that uniquely defines a
chemical element

consists of a central nucleus that is

surrounded by one or more electrons
 Sub-atomic particles
3 sub-atomic particles:
1. Proton
2. Neutron
3. Electron
The protons and neutrons are located in the
nucleus. They are collectively called nucleons. The
electrons orbit around the nucleus. They dictate
the size of the atom and they are responsible for
formation of bond.
 Binding Forces Between Atoms
(Intramolecular)
1. Ionic Bond-formed through actual transfer
of electrons.
2. Covalent bond-formed through sharing of
electrons
a. Non-polar- equal sharing
b. Polar bond- unequal sharing
 Binding forces between
molecules/compounds

Cohesion- between similar molecules

Adhesion- between different molecules

 Types of Intermolecular Attractive Forces

1. Van der Waal’s Forces -forces of attraction that

binds covalent molecules
a. Dipole-dipole(Keesom forces) -2 polar
molecules

 Molecules involved are polar with permanent

dipoles
 Molecules align themselves so that the opposite
partial charges are near and attract each other
b. Dipole-induced dipole (Debye forces)-attractive
force between a polar and a non-polar
molecule
 Transient dipole induced by a permanent dipole
 Polar molecules can produced a temporary
electric dipole in nonpolar molecules
 Example=ethyl acetate and ether
c. Induced dipole-induced dipole(London/ Dipersion
forces)- 2 non-polar molecules
 Induce polarity between non-polar
 Responsible for the liquifaction of gases
 Examples-CS2, CCl4, hexane
2. Hydrogen Bonds
a. intermolecular- between molecules
b. intra-molecular-in the same molecule
Electrostatic interaction of H with highly
electronegative atoms (S,N,Cl, F,O)
3. Ion-dipole- attractive force between an
ionic com pound and a polar compound.
Ex. NaCl and water
Explains solubility of ionic substances in
water
4. Ion-induced dipole- between an ionic
compound and a non-polar compound
Induced by proximity of a charged ion to
a non-polar molecule
this explains the solubility of iodine
crystals in the presence of KI.
 Interacting molecules or ions

Are polar no yes Are polar no

no Ions are involved
molecules molecules
involved? and ions
both
present?
yes

Are hydrogen
yes
atoms bonded to
N, O or F?

no yes

London Dipole- Hydrogen Ion-dipole Electro-

Forces dipole bonding forces static
forces
 Quick Test
1. Which of the following pairs of substances
exhibits London Dispersion Forces?
A. Water-Ethanol
B. Water and Benzene
C. Benzene and Hexane
D. NaCl and water
2. A type of Van der Waals forces of attraction
that results from the tendency of molecules to
align themselves with the oppositely charged
ends of their neighbors
A, Debye
B. London
C. Keesom
D. H-bond
3. A type of Van der Waals forces of attraction
which involves permanent dipoles inducing
polarity in non-polar molecules.
A. Debye
B. London
C. Keesom
D. H-bond
4. A type of Van der Waals forces of attraction
which involves dispersion of charges to induce
polarity between non-polar molecules:
A. Debye
B. London
C. Keesom
D. H-bond
5. The intermolecular forces of attraction
responsible for the solubility of non-polar
molecules such as iodine in solution by the
addition of salts:
A. Debye
B. Ion-dipole forces
C. Ion-induced dipole interaction
D. H-bonds
6. This is responsible for the solubility of ionic
crystalline substance in polar solvents like water
A. Debye
B. Ion-dipole interaction
C. Ion-induced dipole interaction
D. H-bonds
Physical Properties of Matter
 Physical Properties of Matter

• Intensive • Extensive
 Depends on the kind of  Depends on the
matter present and quantity of matter in
independent of the the system
amount  Mass, length, volume
 Temperature, pressure,
density, viscosity,
surface tension, specific
gravity
Classification of Physical Properties
1. Additive Property -depends on the sum of
the individual properties of the components
present in a system (ex. MW)
2. Constitutive Property- depends on the type
and arrangement of the components present
in a system (viscosity, refractive index, optical
activity)
3. Colligative- depends on the number of
components present in a system
 States of Matter
1. Solid
2. Liquid
3. Gas
4. Plasma –aka Mesophase, Liquid Crystal,
Supercritical fluid
- part solid and part liquid
-tend to flow like liquid under extreme
conditions
 The Gaseous State
Laws Governing Gases
1. Boyle’s Law- relationship of P and V at
constant temperature.
P1V1= P2V2
2. Charle’s Law – relationship of V and absolute
T at constant pressure
V1T2 = V2T1
 Gas Laws
3. Amonton’s or Gay Lussac’s Law- relationship pf P and absolute
temperature at constant volume
P1T2=P2T1
4. Combined Gas Law
P1V1T2= P2V2T1
5. Avogadro’s Law- the volume occupied by a gas is directly
proportional to the number of moles.
- at STP, mthe volume occupied by 1 mole of any gas is
equal to 22.4L
6. Ideal gas law
PV=nRT
PVMW=gRT
PMW= dRT
 Gas Laws
7. Graham’s Law – the rate of effusion of a gas is
inversely proportional to the square root of
the molecular weight or the density of the
gas.
8. Dalton’s Law of Partial Pressures- The total
pressure exerted by non-interacting gases is
the sum of their partial pressures.
 Van der Waal’s equation
Behavior of Real Gases is described by the van
der Waal’s equation. Real gases:
a. not composed of infinitesimally small
particles
b. particles are non-elastic
c. they attract to a certain extent
 Real Gas laws
Van der Waal’s Equation for Real Gases

(P+ n²a )(V-nb) = nRT

V²

a/v²= accounts for the internal pressure per mole

resulting from the intermolecular forces of
attraction between the molecules
B= accounts for the incompressibility of the
molecules
 Kinetic Moleular Theory

1. Gases are composed of particles called

atoms or molecules, the total volume of
which is negligible in relation to the volume
of the space to which the molecules are
confined.(condition: low pressure, high
temp.)
2. The particles of the gas do not
attract.(condition: low pressure)
 Kinetic Moleular Theory
3. The particles exhibit continuous random
motion owing to their kinetic energy.
E= 3/2 RT
4. The molecules exhibit perfect elasticity, that
is, there is no net loss of speed or transfer of
energy after they collide with one another and
the walls of the container.
 Fundamental Kinetic Equation
PV= 1/3 nmc2

where: P= pressure
m = mass
c = average velocity
n= no. of molecules
Or root mean square velocity= square root of 3RT/M
 Problem
Calculate the root mean square velocity of
oxygen (molecular weight), 32.0) at 25C
R value is 8.314
 Quick test
1. Using the ideal gas law, compute for the
volume of a mole of gas at a temperature of
18⁰C at 10 atm pressure
2. In the assay of ethyl nitrite spirit, the nitric oxide
gas that is liberated from a definite quantity of spirit
and collected in a gas burette occupies a volume of
30.0 mL at a temperature of 20C and a pressure of
740 mmHg. Assuming the gas is ideal, what is the
volume at 0C and 80 mm Hg?
3. What is the volume of 2 moles of an ideal gas
at 25C and 780 mm Hg/
4. What is the volume of a gas that weighs 7.4
grams with a molecular weight of 44 g/mol at
STP.
5. What is the weight of a gas that has a MW of
54.5 g/mol and a volume of 10L at STP
6 If 0.30 g of ethyl alcohol in the vapor state ,occupies
200 mL at a pressure of 1 atm and a temperature of
100C, what is the molecular weight of ethyl
alcohol? Assume that the vapor behaves as an ideal
gas.
7. This law relates the volume and pressure of
given mass of gas at constant temperature.
A. Boyles
B. Charles
C. Gay-Lussacs
D. Ideal gas law
8. A gas law which states that gases of equal
volumes at the same temperature and pressure
contain the same number of molecules.
A. Boyles
B. Charles
C. Gay Lussacs
D. Avogadros
9. A 50.0 ml sample of oxygen gas is collected at
26oC and a pressure of 710 torr. What volume
will the gas occupy at standard conditions.
10. Calculate the no. of moles in a deep breath
of air whose volume is 2.55 L at body
temperature, 37oC and a pressure of 740 torr.
11. The ff. is are statements regarding the kinetic
molecular theory
I. Volume of gas is negligible in relation to the volume
of the space in which the gas is confined.
II. Particles exhibit continuous random motion owing
to their kinetic energy
III. Speed is lost every time particles go into collision
with each other or with the walls of the vessel.
A. I only
B. I and II
C. II and III
D. III only
12. This equation is used for real gases, where it
accounts for the interactions of gas molecules
hence affecting the pressure and volume of an
ideal gas.

A. Ideal gas equation

B. Van der Waals equation
C. Noyes Whitney equation
D. Freundllich equation
14. This law gives the relationship between the
total pressure in a mixture of gases and the
partial pressure of the individual gases.

A. Ideal gas law

B. Raoult’s Law
C. Grahams Law
D. Dalton’s Law
15. Accounts for the internal pressure per mole
resulting from the intermolecular forces of
attraction between molecules

A. a/v²
B. b
C. p
D. v
 Gases of Pharmaceutical
Importance
1. Oxygen
Oxygen is used extensively in medical
practice to increase oxygenation in patients
with acute and chronic lung disease and
cardiac disorders, for resuscitation, and for
the treatment of victims of poisoning. It is
always administered during anaesthesia.
 Gases of Pharmaceutical
Importance
2. Nitrous oxide
Nitrous oxide also known as “Laughing Gas” is a non
irritating anaesthetic gas also used as a carrier for the
volatile anaesthetics. It may be used to insufflate
body cavities and in cryosurgery as a refrigerant. It
can also be used as an analgesic
 Gases of Pharmaceutical
Importance
3. Carbon dioxide
Carbon dioxide regulates the rate of breathing.
The occupational exposure limit is 5000 ppm. As the
concentration of carbon dioxide rises so dose the
rate of breathing, at 2% the rate is noticeably above
normal, at 10 breathing is very rapid, headache
vomiting and death may occur in an unfit person,
15% will cause unconsciousness in a few minutes,
25% leads to rapid circulatory insufficiency and
death.
THE LIQUID STATE
 Liquids
• Possess less kinetic energy than do gases
• Occupy a definite volume
• Take the shape of the containers that hold
them
• Denser than gases
• Not compressible
 Liquefaction of Gases
• Achieved by lowering the temperature (gas
molecules loss some of its kinetic energy) and
increasing the pressure (molecules come
nearer together and are brought within the
sphere of intermolecular attraction)
• Liquefaction cannot occur if the temperature
is elevated sufficiently irrespective of the
pressure applied.
Methods of Achieving Liquefaction
• Use of freezing mixtures which will cause the
gas to be subjected to very low temp.
• Dewar and vacumm flask
• Compression (Joule Thomson effect)

Application: preparation of aerosols

Critical temperature- the temperature above
which a liquid above which a liquid can no
longer exist.
Critical pressure- the pressure required to liquify
a gas at its critical temperature.

Critical temp and pressure is dependent on

IMAF.
H2O- CT= 374C= 647K CP=218 atm
He CT= 5.2K CP= 2.26 atm
 Clausius-Clapeyron’s equation
-gives the relationship of vapor pressure and the
absolute temperature

Log P2/P1= ΔHv (T2 - T1)

___________
2.303 RT1T2
ΔHv = molar heat of vaporization=heat absorbed by
one mole of a liquid when it is passes to the
vapor state.
 Vapor Pressure of Liquids
When the rate of condensation equals the rate of
vaporization at a definite temperature, the vapor
becomes saturated and a dynamic equilibrum is
established. The pressure of the saturated vapor
above the liquid is then known as the equilibrum
vapor pressure.
-The presence of a gas, such as air, above the liquid
would decrease the rate of evaporation, but it
would not affect the equilibrum pressure of the
vapor.
-an increase in temperature causes an inc. In vapor
pressure
 Problem
1. Compute the vapor pressure of water at 120C .
The vapor pressure, p1, of water at 100C is 1
atm and ΔHv= 9720 cal/mole for this temperture
range.
R=1.987 cal/K
2. The vapor pressure of water at 100C is 76 cm Hg
and at 90C it is 52. 576 cm Hg. Using the
Clausius-Clapeyron equation, calculate the heat
of vaporization of water in cal/mole within this
temperature range.
 Problems
3. Isoflurane and halothane are non-flammable
volatile liquids used for general anesthesia.
What is the vapor pressure of isoflurane at
room temperature, 25C? The heat of
vaporization of isoflurane at its normal boiling
point , 48.5C and at a pressure of 1 atm is
9000cal/K.
 Methods of Determining Vapor
Pressure
1. Manometer
2. Isopiestic Method- used for precise
determination of vapor pressure
3. Thermoelectric method- measures change in
potential as a solution of known vapor
pressure and an unknown evaporate in a
chamber maintained at constant humidity.
3. Boiling point/heat of vaporization
Boiling point- the temperature at which the
vapor pressure is equal to the atmospheric
pressure.

Heat of vaporization- heat supplied at the

boiling point to effect the vaporization of the
substance.
4. Freezing point/Heat of fusion
Freezing point- the temperature at which
there is an equilibrium between the solid and
the liquid phases

Heat of fusion- takes place when freezing

takes place with the evolution of heat. In
order to melt the substance, heat must be
supplied.
5. Surface Tension
- force which reduces the surface area of a
liquid to a minimum
- increase in temperature, increase in kinetic
energy, decrease in surface tension
- substances of high surface tension exhibit
capillary action.
 Methods of Measuring Surface
Tension
1. Capillary rise method
upward pull = 2πr2δcos θ
downward pull = h π r2dg

upward pull = downward pull

δ= ½ hrdg

Relative δ: δ1 = h1d1
δ2 = h2d2

δwater = 72 dynes/cm
6. Viscosity (η)
- reciprocal of fluidity
- force of friction that tends to retard
movement in a fluid body.
- resistance of a liquid to flow
- the greater the liquid viscosity, the more
it flows
Types of Viscosity

1. Absolute viscosity- inate to the liquid

2. Relative viscosity-viscosity in relation to a
standard
3. Kinematic vioscosity- absolute viscosity
divided by the density of the liquid at a
specific temperature.
- expressed as stokes or centistokes
 Measurements of Viscosity
1. Capillary viscosimeter- the viscosity of a
Newtonian liquid can be determined by
measuring the time required for the liquid to
pass between two marks as it flows by gravity
through a vertical tube (Ostwald
Viscosimeter)
η1d2t2= η2d1t1
Problem: Assume that the time required for
acetone to flow between the two marks of the
capillary viscometer was 45 sec., and for the
water the time was 100 sec. at 25oC. The
density of acetone is 0.786 g/cc and that of
water is 0.997 g/cc. The viscosity of water is
0.8904 cp at this temperature. Determine the
viscosity of acetone.

Ans: 0.316 cp
2. Falling sphere (Hoepller falling ball)- a 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 fall is an
inverse function of the viscosity of the sample.
η= t (Sb-Sf) β
where: t= time interval in seconds for the ball to
fall between the two points, Sb and Sf are the
specific gravities of the ball and the fluid, is a
constant for a particular ball.
3. Cup and Bob Viscometer- the 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.

Ex. Searle type- uses a stationary cup and

rotating bob
Couette type- the cup or the bob is either
rotated
4. Cone and Plate Viscometer( Ferranti- Shirley) – the
sample is placed at the center of the plate which is
then raised into a position under the cone.
For Newtonian liquids:
η = C (T/v) where C= constant for the
instrument, T= torque reading, v= speed of the cone
in revolutions/min
For Plastic liquids:
U = C (T-Tf)
v
Where Tf = torque at the shearing stress
Other methods:
5. Brookfield
6. Saybolt
7. Cylinder method (co-axial)
Phase changes gas

Sublimation
Condensation Evaporation

Melting

Freezing
solid liquid
 Solids and the Crystalline State
Crystalline solids
Structural units of crystalline solids like ice,
NaCl and methol are arranged in fixed
geometric pattern of lattices
Have definite shapes and an orderly
arrangement units unlike liquids and gases.
 Crystal forms

1. Cubic - NaCl
2. Tetragonal - Urea
3. Hexagonal - Iodoform
4. Rhombic - Iodine
5. Monoclinic - Sucrose
6. Triclinic - Boric acid

X-ray diffraction- is a method of crystal lattice

determination
 Polymorphism
Definition- substances that exists in more than 1
crystalline form.
-they have different melting points, x-ray
diffraction patterns and solubilities
Types of polymorphism
1. Enantiotropic- when a change from one polynorphic
form to another is reversible
A + B ======= A + B
2. monotropic- when the transition takes place in one
direction
A -------------- B
 Examples
1. Theobroma oil/Cacao butter- use as a suppository
base
a. unstable gamma form melt – 18o
b. alpha form melt- 22o
c. beta prime form melt- 26o
d. stable beta form melt- 34.5o

Note: 33o -the lowest possible temperature to melt cacao

and to prevent the crystal nuclei from destruction.
35o- stable beta crystal destroy
 Examples
2. Different polymorphs of drugs shows different
solubilities- may explain dissolution rates and
activity of drugs.
Ex. Sulfameter- form II more active orally in human
than form III which is more available in the market.
Polymorph of chloramphenicol palmitate has a
significant influence on the biologic activity
Cortisone acetate- 5 different forms and 4 are
unstable in the presence of water due to caking,
heating or grinding under water
Tamoxifen citrate- antiestrogenic and antineoplastic drug used to
treat breast cancer and post menopausal symptoms
form A- metastable polymorph ( less organized)
form B- stable one held by hydrogen bonding

Estrogens- essential hormones for the development of

female sex characteristics
- based on studies the crystals (4) forms found
contain solvent molecules and classified as SOLVATES
rather than polymorph solvates are sometimes called
PSEUDOPOLYMORPHS
 Amorphous Solids
 Considered as supercoiled liquids in which the
molecules are arranged in random manner
 Do not have a definite melting point
 Have faster rate of dissolution than crystalline solids
Types:
1. Isotropic- exhibit similar properties in all directions.
Ex. amorphous substance and cubic crystals.
2. Anisotropic- showing different characteristic
(electric conductance, refractive index, rate of
solubility) in various directions along the crystal.
Examples:
Beeswax and paraffin- appear to be amorphous,
assume crystalline arrangement when heated
and then allow to cool slowly.

Petrolatum- contains both crystalline and

amorphous
Antibiotic(Novobiocin acid)- crystalline
form/amorphous form
 Liquid Crystalline State
(Mesophase)

Mesophase- considered as the fourth state of matter

Structure of Liquid Crystals:
 Are mobile in three (3) directions and can rotate about
three axis perpendicular to one another.
 Molecules are immobile and rotations are not possible
 Intermediate states of mobility and rotation exist and
constitute the liquid crystalline phase or mesophase
 Types of liquid crystals
1. Smectic (soap or grease-like)- molecules are mobile
in two directions and can rotate about one axis.
- has pharmaceutical significance (forms ternary
mixtures or complex mixtures containing a
surfactant, water and weakly ampiphilic or non-
polar additive
2. Nematic (thread-like)- molecules rotate in one axis
but are mobile in three dimensions
3. Cholesteric state- a special type of the nematic type.
Ex. it is exhibited in plaque formatiion in
atherosclerosis whein lipids are incorporated in
human subendothelial macrophages.
Substances that form mesophase (Remember ROPE
• Rigid
• Organic
• Possess strong dipoles and easily polarizable
• Elongated and rectilinear in shape

Mesophase result from:

• Heating solids (thermotropic liquid crystals)
• Action of certain solvents on solids (lyotropic
liquid crystals)
 Properties and Significance of Liquid Crystals

1. Molecules are mobile and their molecules have

flow properties like liquids
2. Birefringence- the light passing through them is
divided into two components with different
refractive indices.
3. Show consistent color changes and therefore used
to detect areas of elevated temperature under the
skin that may be due to a disease process.
 Properties and Significance of Liquid
Crystals

4. Nematic liquid crystals are sensitive to electric

fields (used as sensors)
5. Smectic mesophase has application in the
solubilization of water-insoluble materials.They
are also use to enhance physical stability of
emulsion
 Liquid crystalline substances

1. Lipoidal forms found in nerves, brain tissue, and

blood vessels
2. Three components of bile(bile acids, salt and water)
in proper proportion forms smectic mesophase
which may be involved in the formation of
gallstones
3. Non-aqueous lipid crystals- triethanolamine, oleic
acid with a series of polyethylene glycols or various
organic acids.
DISPERSED SYSTEMS
Classification of Dispersed Systems

Type Particle size range

Molecular Dispersion <1.0 nm

Colloidal Dispersion 1.0 nm -0.5 um

Coarse Dispersion >0.5 um

 1. True Solutions
• Is defined as a mixture of two or more
components that form a homogeneous
molecular dispersion or one phase system
• Paticle size < 1 nm
 Types of Solutes
Electrolyte Non-electrolyte
Yield ions Do not yield ions
Conduct electricity Do not conduct
electricity
Ex. NaCl, HCl, Ex. Sucrose, urea,
CH3COH glucose
 DISSOLUTION VS. SOLUBILITY
Dissolution
• TRANSFER of molecules or
ions from a solid state into
solution
• Is described by the Noyes-
Whitney Equation
Solubility
• EXTENT to which the
dissolution proceeds under
a given set of experimental
conditions
Classifications of solutions
1. Saturated- one in which the solute is in equilibrium
with the solid phase
2. Unsaturated- one containing the dissolved solute in a
conc. Below that necessary for complete saturation
at a definite temperature
3. Supersaturated- one containing more of the dissolved
solute that it would normally contain at a definite
temperature where the undissolved solute is
present.
 Expressions of solubility

1. USP & NF- no. of mL of solvent which

dissolves 1 gram of a substance
2. Molality
3. Molarity
4. % concentrations
 Terms of Approximate Solubility
Term Parts of solvent required per 1
part of solute
Very soluble Less than 1 part
Freely soluble 1-10 parts
Soluble 10-30 parts
Sparingly soluble 30-100 parts

Slightly soluble 100-1,000 parts

Very slightly soluble 1,000-10,000 parts
Practically insoluble More than 10,000 parts
 Factors affecting solubility
1. nature of solute and solvent
A. Solubility in polar solvents:
1. dipole moment ( inc. DM, inc. solubility)
- polar solvent dissolves ionic solutes
and other polar substances
2. ability to form H-bonding
3. Structural features- ratio of polar to non-
polar groups of the molecules.
ex. length of C chain and branching
Polar solvent like water act as solvent accdg. to
the ff. mechanisms:
1. Polar solvents break covalent bonds of
potentially strong electrolytes by acid-base
reaction
2. Capable of solvating molecules and ions
through dipole interaction forces particularly
H-bonding
3. Polar solvents have high dielectric constant.
Non-polar solvents:
1. Have low dielectric constant
2. Unable to break covalent bonds and ionized
weak electrolytes they belong to a group of
aprotic solvents.
3. Cannot form hydrogen bridges with non-
electrolyte
4. They can dissolve non-polar solutes with
similar internal pressures through induce
dipole interaction.
Semi-polar solvents: Ketones and alcohols
1. Can induce a certain degree of polarity in
non-polar solvent
2. Act as intermediate solvent to bring about
miscibility of polar and non-polar liquid.
Ex. acetone increase the sol of ether in water
-alcohol increase sol of water in castor oil
- PEG inc. solubility of water in peppermint
oil
 Solubility of Liquids-Liquids

2 categories of liquid-liquid systems:

1. complete miscibility
2. partial miscibility
Factors affecting mutual miscibility of partially
miscible liquids:
a. Solubility increases with increase in T until CST
or UCT is reached.
b. Influence of foreign substance
 Solubility of Solids in Solids

Terms:
Solvation-interaction of solvent with solute.
Blending-increase in mutual solubility of 2
partially miscible liquid by an addendum
Micellar Solubilization- increase in water
solubility of non-polar liquid by micelle
forming surfactant
 Factor that affect solubility
2. Temperature
ENDOTHERMIC REACTION EXOTHERMIC REACTION
• Absorb heat • Release heat
• Increased temperature, • Decrease temperature,
increased solubility increased solubility
• Ca(OH)2
 Factor that affect solubility
3.pH
Critical pH for a weak acid Critical pH for a weak base
• Is the pH below which the • Is the pH above which the
weak acid precipitates from weak base precipitates from
solution as the solution as the
undissociated form undissociated form
 PHASE EQUILIBRIA AND THE
PHASE RULE

Phase rule- formulated by J Williar Gibbs

- a useful device for relating the effect of
the least number of independent variables (T, P and
conc) upon various phases (S,L,G) that can exist in
equilibrium system containing a given number of
components
F= C-P +2 where: F= # of degrees of freedom, C= # of
components and P= # of phases present
1. # of phases- number of homogeneous, physically distinct
portion of a system that is separated from other portions of
the system by boundary surfaces.
Ex. water and its vapor- two phase system

2. # of components- smallest number of constituents by which the

composition of each phase in the system at equilibrium can be
expressed in the form of chemical formula or equation.
Ex. # of components at equilibrium for the mixture of ice, liquid
water and water vapor is one .
3. # of degrees of freedom-least number of intensive variable (T,P
conc, ref. index, density, viscosity etc. that must be fixed to
describe the system completely
 Problems:
1. Determine the degrees of freedom of a system
containing either ice, water or water vapor.
F= C-P + 2
F= 1-1 + 2 = 2 (bivariant)
2. Calculate the degrees of freedom for a system
containing water in equilibrium with its vapor.
F = 1-2+2 = 1 (univariant)
 Problems
3. What will be the degrees of freedom if liquid
water and its vapor is cool until 3rd phase
separates out, so the system contains ice,
water-water vapor in equilibrium
F= 1 – 3 +2 = 0 (invariant)
 Exercises
1. Calculate the degrees of freedom of liquid water
and its vapor.
2. Determine the degrees of freedom of a system
containing liquid ethyl alcohol and its vapor
3. What is the degrees of freedom for a system
containing liquid water + liquid ethyl alcohol +
vapor mixture.
4. Calculate the degrees of freedom of a system
containing liquid water + liquid benzyl alcohol +
vapor mixture
 Application of the Phase rule to a Single
Component Systems

System Number of Degrees of Comments

Phases Freedom

Gas, liquid, solid 1 2 System is bivariant, Point D

Gas-liquid 2 1 System is univariant, A-O, B-O, C-

Liquid-solid O
Or gas- solid

Gas-liquid-Solid 3 0 Invariant, Point O

COLLIGATIVE PROPERTIES OF
SOLUTIONS
1. Vapor Pressure Lowering
• When a non-volatile solute is added to a
volatile solvent, the solute reduces the
escaping tendency of the solvent
• Thus the vapor pressure of the solution is
lowered proportional to the relative number
of solute molecules
• Raoult’s Law ∆P= P⁰X solute
What is the partial vapor pressure of
benzene and of ethylene chloride in a
solution of a mole fraction of benzene
at 0.6? The vapor pressure of pure
substance at 50C in 268 mm, and the
corresponding PA for ethylene chloride
in 236 mm.
Calculate the vapor pressure lowering.
 Boiling Point Elevation
Boiling Point- is the temperature at which the vapor
pressure of the liquid becomes equal to the external
atmospheric pressure ( 1 atm=760 mmHg)
-The boiling point of a solution containing a non-
volatile solute is higher than the pure solvent
because the solute will lower the vapor pressure of
the solvent.
∆Tb = Kbm
KbH20 = 0.52⁰C/m
3. Freezing Point Depression
• Freezing Point-is the temperature at which
solid and liquid phases are in equilibrum
under an external pressure of 1 atm.
• In general, solutions have a lower freezing
point than the pure solvent

∆Tf = Kfm
Kf H2O= 1.86⁰C/m
 Problems

1. What is the boiling point and freezing point of a

solution prepared by dissolving 2.40 g of biphenyl
(C12H10) in 75.0 g of benzene?. The molecular
weight of biphenyl is 154 g/mole. Kf of benzene = -
5.12oC/molal. F.P.= 5.5oC .Kb of benzene =
2.53oC/molal, B.P. = 90.1C.
2. A solution that contains 14.8 g of napthalene
(C10H8) in 300 g of nitrobenzene freezes at 2.0oC.
The normal freezing point of nitrobenzene is 5.7oC.
What is the freezing point constant of nitrobenzene?
1. Methyl alcohol and ethyl alcohol form an ideal
solution. At 50⁰C, the vapor pressure of pure
methyl alcohol is 0.129 at,. And the vapor pressure
of pure ethyl alcohol is 0.292 atm. What is the
vapor pressure of 50oC of a solution containing
25.00 g of methyl alcohol and 7.56 g of ethyl
alcohol.
2. Calculate the vapor pressure (assuming ideality) of
a 1.0 m aqueous solution of a non-volatile, non-
dissociating solute in water at 500C. The vapor
pressure of water is 0.122 atm?
 Osmotic Pressure (π)
 is the pressure required to offset the
movement of solvent through a
semipermeable membrane.
 Also defined as the pressure required to
prevent osmosis in solution
Π V= nRT
Π = MRT
What is the osmotic pressure of an aqueous
solution that contains 6.00 g urea (CON2H2) in
400 mL of a solution at 20oC?
 Osmotic Pressure
2. What is the osmotic pressure of an aqueous
solution that contains 2.00 g of glucose in 250
mL solution at 25oC?
2. Bronsted Lowry Theory
Acid – is a substance (charged or
uncharged) that is capable in donating a
proton.
Base- is a substance (charged or uncharged)
that is capable of accepting a proton from an
acid.
Isotonic Solutions
Isotonic Solution- same osmotic pressure as a
specific body fluid like blood and the body fluid
of the eyes, nose, bowel
-Products that requires the same tonicity with
biologic fluids are opthalmic, nasal, parenteral,
and some rectal preparations
 Methods of Adjusting Isotonicity
Class I- Addition of a tonicity adjusting agent
Sodium chloride Equivalent Method/E value
Method
Freezing Point Depression method/Cryoscopic
method
Class II-Addition of water and dilution with
buffered isotonic solution
White Vincent method
Sprowl’s method
 Isotonicity Adjustment by NaCl
Method

• Most frequently used method in the

calculation of the amount of sodium, chloride
needed to prepare isotonic drug solution
Find the quantity of sodium chloride required in
compounding the following prescription. The
sodium chloride equivalent of cocaine HCl is
0.16.
Rx
Cocaine HCl 0.2
Sodium chloride q.s.
Purified Water ad 30.0
Make isoton sol.
Sig. One drop in each eye
Find the quantity of sodium chloride to be used
in compounding the following prescription. The
sodium chloride equivalent of ephedrine sulfate
is 0.23.
Rx
Ephedrine sulfate 0.5
Sodium chloride q.s
Purified Water ad 50.00 mL
Make isoton, sol.
Sig, Use as directed
Find the quantity of sodium chloride to be used
in compounding the following prescription. The
values of sodium chloride equivalent of
.epinephrine HCl and scopolamine HBr are 0.29
and 0.12 respectively
Rx
Epinephrine HCl 1%
Scopolamine 0.5%
Sodium chloride q.s.
Purified Water ad 60.0
Make isoton. Sol.
Sog. Use in the eye
 TONICITY AGENTS OTHER THAN
SODIUM CHLORIDE
• Such as dextrose or Boric acid
• Additional step in the calculation process.
Divide the amount of NaCl required by the E
value of the tonicity agent to be used.
Find the quantity of Boric acid (in grams ) to be
used in compounding the following prescription.
Boric acid E value=0.52 , Atropine =0.13

Rx
Atropine Sulfate 1%
Boric Acid q.s.
Purified Water ad 30.0
Make iston. Sol
Sig. One gtt in each eye
 The Freezing Point Depression
• Dependent on the number of particles in
solution

• Blood plasma has a freezing point of -0.52C

Compound the prescription: Freezing point
depression (Tf) of 1% atropine sulfate is 0.07
Rx
Atropine sulfate 1%
Sodium chloride q.s.
Purified Water ad 100
Make isoton. Sol.
Sig. One drop in each eye
 White Vincent Method
• Provide a method for readily finding the
correct volume of water in which to dissolve a
drug to produce a solution iso-osmotic with
tears
• Followed by the addition of an isotonic vehicle
to bring the solution to its final volume

V= w X E * 111.1
Make the following solution isotonic:
Rx
Procaine HCl 1% E= 0.21
Sodium chloride q.s
Purified water 60
Make the following prescription isotonic with
tears:
Rx Ephedrine sulfate 0.5 E=0.23
Boric acid 0.2 E= 0.52
Ammonium chloride 0.25 E= 0.25
Purified water ad 60.0
 Sprowls Method

V= 0.3g x E x 111.1
3. Lewis Theory
Acid- is a molecule or ion that accepts an
electron or from another atom.
Base- is a substance that denotes an
electron pair to be shared with another
atom
ACID-BASE EQUILIBRIA
 3 Concepts of Acids and bases

CONCEPT ACIDS BASES

Arrhenius Yields H+ Yields OH¯

Bronsted Lowry Proton donor Proton acceptor

Lewis Electon pair Electron pair

acceptor donor
 Sample Problem on pH/pOH
If the hydrogen ion concentration of a solution is
0.0265M, what is its pH?

If the hydroxide ion concentration is 0.0034,

what is its pH?
 Buffers
Buffers- compounds or mixture of compounds
which by their presence in solution resist
change in pH upon addition of small amount
of an acid or a base.

Buffer Action- ability to resist change in pH

Buffer Equation- Henderson Hasselbalch

Equation
• Most buffers used in pharmacy are acid
buffers. Basic buffers are not used due to
their:
1. volatility
2. instability
3. dependence of their pH on pKw which
is also dependent on temperature
 Methods of Determining pH
1. Colorimetric- used to determine pH of
aqueous solutions which are not colored or
turbid.
Ex. pH paper, Clark-Lube buffers, colors of
buffers of known pH are matched with the
color of the unknown solution
2. Potentiometric- use of pH meter
Buffer capacity- magnitude of the resistance of a buffer
to pH changes (known as buffer efficiency, buffer
index and buffer value)
- concept introduced by Van Slyke

Buffer is most efficient:

1. when the concentration of the salt is equal to that
of the acid
2. efficiency of a buffer increase as the value of log of
the ratio of the concentration of salt and acid is
equal to zero.
 Buffers in Pharmaceutical and Biological
System
1. Blood- pH 7.4 and maintained by the
primary buffer in the plasma and the
secondary buffers in the erythrocytes
2. Plasma- carbonic acid/ bicarbonate and
phosphate buffers
 Problems
1. The dissociation constant of acetic acid is 1.75
x 10⁻⁵. Calculate the pKa.

2. What is the pH of the buffer solution

prepared with 0.075M sodium borate and 0.008
M boric acid? The pka of Boric acid is 9.24 at
25⁰C.
3. What is the pH of a buffer solution prepared
with 0.05 M ammonia and 0.05M ammonium
chloride? The Kb value of ammonia is 1.80 x
10¯⁵ at 25⁰C.
COLLOIDS
Dispersed Systems- consist of particulate matter,
the dispersed phase and the dispersion
medium ( continous phase).

Types of Dispersed System

1. Molecular dispersions
2. Colloidal Dispersions
3. Coarse Dispersions
 Classification of Dispersed Systems on
the basis of Particle size
Class Range of Particle Characterisitcs of System Examples
Size
Molecular Less than 1 nm 1. Invisible in electron microscope Oxygen
Dispersion 2. Pass through ultrafilter and molecules,
semipermeable membrane ordinary ions,
3. Undergo rapid diffusion glucose
Colloidal From 1 nm to 0.5 1. Not resolved by ordinary microscope Colloidal silver
Dispersion um ( but can be detercted under ultra- sols, natural and
microscope) synthetic
2. Visible in electron microscope polymers,
3. Pass through filter paper cheese, butter,
4. Do not pass semipermeable jelly, paint, milk ,
membrane shaving cream
5. Diffuse very slowly
Class Range of Particle Characterisitcs of Examples
Size System

Coarse Dispersion Greater than 0.5 1. Visible under Grains of sand,

um microscope most
2. Do not pss pharmaceutical
through normal emulsions and
filter suspensions, red
3. Do not dialyze blood cells
through
semipermeable
membrane
4. Do not diffuse
 Methods of Separating Colloids
- Dialysis
- Electrodialysis
- Ultrafiltration

- Colloidal systems- all kinds of dispersed phase

might form colloids in all possible kinds of
media except for a gas-gas combination, bec.
all gases mix uniformly at the molecular level,
gases only form solutions with each other.
 Types of Colloidal System
1. Lyophilic colloids-easy to prepare, have greater
stability
- Solvent-loving
- Interacts appreciably with the dispersion medium
- Form colloidal dispersions or SOLS
Examples:
a. hydrosol-acacia, gelatin, insulin, albumin
b. Organosol- polystyrene, rubber
c. Aerosol- solid/liquid in gaseous medium
2. Lyophobic colloids
-solvent-hating colloids
-materials with little or no attraction for the
dispersion, due to the absence of a solvent
sheath around the particle
-composed of inorganic particles dispersed in
water
Examples: gold, silver, sulfur, silver iodide
3. Association Colloids
-ampiphilic or surface-active agents
-characterized by having two distinct regions of
opposing solution affinities within the same
molecule or ion.
-aggregates of subcolloidal particles are called
micelles
-ampiphiles may be anionic, cationic, nonionic
or ampholytic( zwitterionic)
 Properties of Colloids
1. Optical Property
- Faraday- Tyndall Effect
2. Kinetic Property
a. Thermal
- Brownian movement
- Diffusion (Fick’s law)
- Osmotic pressure
b. Gravitational- sedimentation (Stoke’s law)
c. Applied external
- Viscosity
3. Electrical property
-electrophoresis
Electroosmosis
Sedimentation potential
Streaming potential
INTERFACIAL PHENOMENA
 Interfacial Phenomena
• Attributed to the effects of the molecules
found at the interface between 2 phases.
 Surface and Interfacial Tension
PHENOMENON INTERFACE UNIT

Surface tension L-G Dyne/cm

S-G

Interfacial S-S
Tension L-L Dyne/cm
S-L
 Griffin Hydrophilic-Lipophilic
Balance(HLB) System
HLB Value Range Surfactant Application
0-3 Antifoaming Agents
4-6 w/o emulsifying agents
7-9 Wetting agents
8-18 O/w emulsifying agents
13-15 Detergents
10-18 Solubilizing agents
 Rheology
Rheology- comes from the word rheo( to flow) and
logus(study)
- this term was suggested by Bingham and
Crawford

Principles are used to study:

• Paints & inks
• Doughs
• Road building materials
• Cosmetics
• Dairy products
• Dilute and concentrated colloidal system
Type Description Examples

Anionic Long chain molecules of Sodium lauryl

carbohydrates, sulfates and sulfate
sulfonates
Cationic Interactions with negatively charged Benzalkonium
surfaces such as cell membranes, chloride
cytotoxic, used as antimicrobial
preservatives
Amphoteric Are zwitterions Polypeptide,
lecithin,
cephalin
Non-ionic Long but contain a small alcohol base Fatty alcohols,
such as propylene glycol, sorbitan, or laury,cetyl
glycerol to which fatty acids are esters
attached to form the fatty acid esters
 Wetting Phenomenon
• Contact angle that a droplet of the liquid
makes with the solid surface at the point of
contact
• 0⁰ = wetting
• 180⁰ = completely non-wetting- particle is in
contact with the liquid at one point
 Wetting Phenomenon
PROCESS SURFACE FREE ENERGY
CHANGE
Adhesion Solid/Liquid in contact

Spreading Liquid on solid surface

Immersion Solid in Liquid

RHEOLOGY
 Rheology
• Greek terms rheo “to flow” and logos “study”
• Scientific study of the deformation and flow
properties of matter
• Elasticity, fluidity, viscosity
 Newtonian Flow
• Has linear relationship between shear rate
and shear stress
• Constant viscosity with increasing rate of
shear
• Ex. Water, ethanol, acetone, glycerine,
benzene
 II. Non-Newtonian Flow
A. Shear dependent Viscosity
Plastic
Pseudoplastic
Dilatant

B. Time dependent Viscosity

Thixotropy
Rheopexy
 Plastic Flow
• Bingham bodies
• A yield value must be overcome before the
system begins to flow
 Pseudoplastic Flow
• Shear thinning systems
• Curve begins at the origin
• No yield value
• Viscosity decreases with increasing shear rate
• Ex. Polymer solution, Na alginate,
pentylcellulose, PEG
 Dilatant Flow
• Shear thickening system
• Reverse effect to pseudoplastic flow
• Viscosity increases with increasing rate of
shear
• Starch in water, conc. Suspension of inorganic
pigments in water, zinc oxide, barium sulfate ,
titanium dioxide in water.
 Time Dependent
Thixotropy- gel-sol transformation

Rheopexy- sol gel transformation

 Thixotropy
Thixotropic systems usually conatain assymetric
particles that, through numerous points of contact,
set-up a loose three dimensional network
throuighout the sample. At rest, this structure
confer some degree of rigidity on the system, and it
resembles, a gel. As shear is applied and flow starts,
the structure begins to break down as points of
contacts are disrupted and particles become aligned.
The material undergoes a gel-sol transformation. And
exhibits shear thinning . On removal of the stress the
structure starts to reform.
 Rheopexy
It refers to the process of reformation of the gel
structure after it has been deformed that can be
accelerated by applying gentle and regular
movements (roolling or rocking motions).
 Viscoelasticity
• The property of materials wherein these
exhibit both the viscous properties of liquids
as well as the elastic property of solids.
• When materials are subjected to stress for a
period of time they undergo slight
deformation under the influence of the stress
but once the stress is removed, they exhibit
their elastic behavior by returning to their
original shape with little permanent
deformation.
 Application of Viscoelasticity
• Creams
• Lotions
• Ointments
• Suspensions
• Colloidal dispersions
Determination of Rheologic Properties
1. Capillary viscometer

2. Falling sphere viscometer- a glass or steel bar rolls

down an almost vertical glass tube containing the
test liquid at a constant temp. The rate at which a
ball of a particular density and diameter falls is an
inverse function of the viscosity of the sample.
2. Cone and Plate viscosimeter
 Micromeritics
(science and technology of small particles)
Categories of properties:
1. Fundamental Properties- inherent in all individual
particles
-defined individually
Ex. Particles size and shape, particle size distribution,
surface area

2. Derived properties
-dependent on the fundamental properties
Ex. Porosity, density , flow properties, packing
arrangement or bulkiness
 Particle Size
Coarse > 1000 um
Conventional 50-1000 um
Fine 1-50 um
Very fine 0.1-1um
Ultra fine < 0.1um
 Methods of particle Size
Determination
1. Optical Microscopy-use of microscope to
measure individual particles
Adv. Individual particles can be seen
Disadv, very tedious and 2D image only
 3 Measurements
1. Ferett Diameter- distance between two
tangents on opposite sides of the particles
2. Martin Diameter- the length of the line that
bisects the particle image into halves
3. Projected Area of the circle-diameter of the
circle that will enclose the particle
 2. Sieve Analysis
• USP Method
• Sieve/mesh- number of square opening per
linear inch
• Disadvantage- attrition of particles
 3. Sedimentation Method
• Sedimentation rate or free fall velocity of
particles
• Apparatus-Andreasen pipet
 4. Automatic Particle Counters
1. Coulter Counter
Principle: electric resistance (high ER, big
size)

2. HIAC/Royco instrument
Principle-light blockade (high blockade, big
size)
3. Gelman Counter
Principle- Faraday Tyndall Effect
B. Surface Area
Methods:
1. Adsorption Method- high ads, high SA

2. Air Permeability Method- high permeability,

low SA
 Derived Properties
A. Fluidity
B. Compressibility
C. Porosity
D. Density
E. Bulkiness
 A. Fluidity-Angle of Repose
Methods:
1. Fixed funnel method
a. Fixed bed cone (constant diameter
b. Free standing cone (constant height)
2. Tilting Box
3. Revolving cylinder

Measure angle of repose = arctan h/r

 Angle of repose
Angle of Repose Interpretation
25-30 Excellent
31-35 Good
36-40 Fair
41-45 Passable
46-55 Poor
56-65 Very Poor
≥66 Very very poor
 Example
Height of cone (fixed funnel)= 7 cm

Diameter of cone formed= 14.5 cm

 B. Compressibility
Bulk and tapped Density
Bulk Density= wt. of sample/Vinitial
Tapped Density = wt. of sample/Vfinal

Compressibility Index= ((Vi-Vf)/Vi ) x 100

Hausner’s Ratio= Vi/Vf

Carr’s Index Interpretation Hausner’s
Ratio
≤10 Excellent 1.00-1.11
11-15 Good 1.12-1.18
15-20 Fair 1.19-1.125
21-25 Passable 1,26-1.34
26-31 Poor 1.35-1.45
32-37 Very Poor 1.46-1.59
≥38 Very very Poor ≥1.60
 Sample Problem
Sodium bicarbonate 100 mg tablet
Evaluation of Granules
Batch Number 0012x
Find Bulk density, tapped density, Carr’s Index
and Hausner’s ratio

Wt. of sample= 60g

Volume of sample untapped=47mL
Volum of Sample tapped= 38 mL
 B. Particle Volume
True /Particle Volume (Vp)=volume of particle w/o empty
space

Granule Volume(Vg)= Vp + intraparticle spaces

Bulk Volume(Vb)= Vg + interparticle spaces

Void Volume(V) = Vb-Vp= inter+intra

 C. Porosity
Єinterspace= (Vb-Vg)/Vb) x 100

Єintraspace= (Vg-Vp)/Vg) x 100

Єtotal = (Vb-Vp)/Vb) x100

 D. Particle Density
True Density= M/Vp

Granule Density= M/Vg

Bulk Density = M/Vb

 E. Bulkiness
Aka : Bulk

Reciprocal of Bulk Density

Important consideration in packaging of

powders
 Sample Problem
Volume of particle= 0.3mL
Intraparticle space= 0.1mL
Spaces between particles= 1.6 mL
Determine: Vg, Vb , єintra, єinter, єtotal
CHEMICAL KINETICS
 Chemical KInetics
• Is the study of the rates of reaction and the
mechanism by which these reactions occur
• It is used to ascertain pharmaceutical product
stability and bioavailability
 Rate of reaction
• Aka: Degradation rate
• Is the velocity or speed with which a reaction
occurs
• Depends on: reactant cocentration,
temperature and pH
 Orders of Rea ction
• Zero order

• First order
 Shelf Life: Zero order
• Is the period of time where 90% of the original
concentration is left and 10% is already
degraded

• T90 = 0.1Co/k0
 Shelf Life: First Order

• T90= 0.105/k
 Problem
The amount of drug remaining after 90 hrs is 5
mg/mL from an initial concentration of 50
mg/mL. Compute for the zero-order rate
constant.
The amount of drug remaining after 180 hrs was
5 mg/mL from an initial concentration of 60
mg/mL. Compute for the first order rate
constant. And half life of he drug.
What is the first order shelf life (in days) of a
drug that has a concentration of 50 mg/mL and
a rate constant of 0.0005/hr.