Mr.

Evan Dykimching, RPh

 basic unit of matter
1. Ionic Bonding
2. Covalent Bonding
1. Van der Waals Forces
2. Ion-Dipole Interaction
3. Ion-Induced Dipole Interaction
4. Hydrogen Bonds
 KEESOM DEBYE LONDON
Dipole-Dipole Dipole- Induced
Induced Dipole-
dipole Induced
dipole
“Alignment” “Induction” Dispersion
or
“Orientation”
A. water – ethanol
B. water – benzene
C. benzene – hexane
D. chloroform – oil

ANSWER: C
 polar molecules are attracted to either
positive or negative charges
 the force of attraction induced by the close proximity
of a charged ion to the nonpolar molecule

I2 + K+I- → K+I3-
nonpolar iodide anion iodide complex
 attraction of a hydrogen atom for a strongly
electronegative atom such as oxygen,
nitrogen, fluorine, chlorine and sulfur
1. A data set in which there is a considerable
closeness among the values
a. Accurate
b. Approximate
c. Estimate
d. Precise
2. A type of Van der Waals forces of attraction 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 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 interaction
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
7. H-bond is the interaction between a molecule
containing a hydrogen atom and a strongly
electronegative atom such as fluorine, oxygen and
nitrogen. This is/are true statements regarding H-bonds:
I. Stronger than ionic bonds
II. Responsible for the formation of a water molecule
III. Can be both occurring as an intermolecular force of
attraction
A. I only B. I and II only
C. II and III only D. III only
E I, II and III
 ADDITIVE CONSTITUTIVE COLLIGATIVE
SUM TYPE NUMBER OF
& COMPONENTS
ARRANGEMENT
• Molecular Weight • Optical rotation • Vapor pressure
• Mass lowering
• Boiling point
elevation
• Freezing point
depression
• Osmotic pressure
 EXTENSIVE INTENSIVE
DEPENDENT INDEPENDENT
OF AMOUNT OF AMOUNT
Example: Example:
Length Specific Gravity
Volume Viscosity
mass per unit volume
D=M/V
Unit: g/mL
1. Absolute
2. Apparent
3. Relative
density of sample / density of standard
 pycnometer method
 USP Method
 ordinary or Geissler
pycnometer

 Mohr-Westphal Balance
1. Molecular Weight
a. Additive
b. Constitutive
c. Colligative
d. All of the Above
2. Refractive Index
a. Additive
b. Constitutive
c. Colligative
d. All of the Above
3. Colligative Property
a. Vapor pressure lowering
b. Boiling point depression
c. Freezing point elevation
d. All of the above
4. Density measured in air
a. Absolute
b. Apparent
c. Relative
d. Volumetric
1. Plasma
2. Gases
3. Liquids
4. Solids
aka: Mesophase, Liquid Crystal
part solid and part liquid
tends to flow like liquid under extreme
conditions
 SMECTIC NEMATIC
“Soap-like “Thread like”
or
Grease-like”
1 axis 1 axis
Mobile in 2 Mobile in 3
direction direction
LYOTROPIC THERMOTROPIC
Using solvent Using heat
 rapid motion
 weak intermolecular forces
 fill all available space
 compressible
 for many, are invisible
1. total volume of gas molecules is negligible
as compared to the volume of space in which
they are confined

2. gas particles do not attract one another but

rather move independently from each other

3. particles exhibit continuous random

movement due to their kinetic energy

4. gas molecules exhibit perfect elasticity

 Boyle’s Law
 Charle’s Law
 Gay-Lussac’s Law
 Combined Gas Law
 Ideal Gas Law
 Van der Waals’ Equation for Real
Gases
an2
(P + --------) (V – nb) = nRT
V2
states that at constant temperature the
SOLUBILITY OF GAS in a liquid is
directly proportional to the PRESSURE
of the gas above the liquid
PTotal = P1 + P2 + P3…
P1 = P1º X1
P2 = P2º X2
Speed of diffusion of gas
speed = 1 / √ d
A sample of gas has a volume of 20 L at 0.2
atm. What will be its volume at 1.5 atm?
What is the molecular weight (in g/mol) of an
unknown gas that weighs 5g at 20ºC, and
occupies 500 mL at 497 mmHg?
This law relates the volume and pressure of
given mass of gas at constant temperature
a. Boyles
b. Charles
c. Gay-lussac
d. Ideal gas laws
The equation V~T or V=kT, was explained by
which gas law?
I. Boyle
II. Charles
III. Gay-lussac
a. I only d. III only
b. I and II only e. I, II and III
c. II and III only
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-lussac
d. Avogadro’s
The following is/are true 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 only
c. II and III only
d. III only
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. Freundlich equation
This states that the rate of diffusion of the gas and
the speed of the gas molecules are inversely
proportional to the square root of their densitiy
a. Ideal gas law
b. Raoult’s law
c. Graham’s law
d. Dalton’s law
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. Graham’s law
d. Dalton’s law
 less kinetic energy than do gases
 definite volume
 take the shape of the containers that
hold them
 denser than gases
 not compressible
pressure of the saturated
vapor above a liquid
resulting from the escape
of surface liquid
molecules
relationship between the vapor pressure
and the absolute temperature of a liquid
Hv(T2-T1)
log (P2/P1) = ---------------------------
2.303R(T1 x T2)
Particulate matter known as dispersed
phase distributed throughout a
continuous phase/dispersion medium
mixture of two or more components
homogeneous molecular dispersion
(one-phase system)
 ELECTROLYTE NON-ELECTROLYTE
YIELD DO NOT YIELD
ions ions
Conduct Do not conduct
electricity electricity
e.g. NaCl, HCl, e.g. Sucrose
CH3COOH
 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
 Parts of Solvent Required to
Term
Dissolve One Part of Solute
Very Soluble Less than 1
Freely Soluble 1 – 10
Soluble 10 – 30
Sparingly Soluble 30 – 100
Slightly Soluble 100 – 1,000
Very Slightly Soluble 1,000 – 10,000
Practically Insoluble or Greater than or equal to 10,000
Insoluble
Saturated
 the solute is in equilibrium with the solid phase

Unsaturated
 the solute is in a concentration below that
necessary for complete saturation
Supersaturated
 the solute is in a concentration above that
necessary for complete saturation

Q: What do you call state where MAXIMUM amount

of solute is dissolved in solvent?
1. temperature
2. pH
3. presence of salts
 Endothermic dissolution
 heat is absorbed
 increased temp, increased solubility

 Exothermic dissolution
 heat is released
 decreased temp, increased solubility
Concept of critical pH or the pH of
precipitation (pHp)

Critical pH of weak ACID:

 is the pH BELOW which the weak acid precipitates
from solution as the undissociated form
Critical pH for a weak BASE
 is the pH ABOVE which the weak base precipitates
from solution as the undissociated form
 Salting-in
 added salt increases the hydrophilicity of the
solution

 Salting-out
 added salt reduces the available amount of water
thus, precipitating the solute
A method used to determine the molecular
weight of easily vaporized liquids
I. Regnault
II. Victor-Meyer
III. Gieger-muller
a. I only d. III only
b. I and II only
c. II and III only
Accounts for the internal pressure per mole
resulting from the intermolecular forces of
attraction between the molecules
a. an2/v2 d. V
b. nb
c. P
Describes the relationship between vapor
pressure and absolute temperature of liquid
a. Graham’s Law d. Clausius Clapeyron
b. Dalton’s Law
c. Henry’s Law
Emulsions
a. True Solution
b. Molecular Dispersion
c. Colloidal Dispersion
d. Coarse Dispersion
Slightly Soluble
a. 10-30
b. 30-100
c. 100-1000
d. 1000-10000
1. Vapor Pressure Lowering
2. Boiling Point Elevation
3. Freezing Point Depression
4. Osmotic Pressure
 ΔTb = Kbm

1000 w2
ΔTb = Kb -------------
w1MW2
 ΔTf = Kfm

1000 w2
ΔTf = Kf -------------
w1MW2
 Osmosis
 Greek: “push” or “impulse”

 movement of water across a

semipermeable membrane
from a region of high to low
water concentration
 is the pressure required
to offset the movement of
solvent through a
semipermeable
membrane

πV = nRT

π = MRT
What would be the boiling point
elevation of a 0.5 m solution of KCl?
The ebullioscopic constant of water is
0.52ºC/m.
What is the boiling point of a solution
containing 50g dextrose (MW: 180) in
1000 mL of water? The molal elevation
constant of water is 0.52.
What is the osmotic pressure (in atm) of
a 0.9 M solution of glucose at 18ºC?
Class I
1. Freezing Point Depression/Cryoscopic Method
2. Sodium Chloride Equivalent/E-Value Method
Class II
1. White Vincent Method
2. Sprowl’s Method
Cryoscopic Method
Isotonic freezing point depression
 0.52C
Isotonic NaCl concentration
 0.9% (w/v) NaCl
How much sodium chloride is required to
render 100 mL of a 1% solution of
apomorphine HCl isotonic with blood serum?
ΔTf of 1% apomorphine HCl = 0.08ºC.
E value
 gram of NaCl equivalent to 1 gram of substance

Isotonic NaCl concentration

 0.9% (w/v) NaCl
Step 1: Calculate NaCl represented by ingredients (A)
Step 2: Calculate NaCl that makes volume isotonic (B)
Step 3: Subtract: B-A = NaCl required
Step 4: If an agent other than NaCl, such as boric acid,
dextrose, sodium or potassium nitrate is to be used
to make a solution isotonic, divide the amount of
NaCl (obtained in Step 3) by the sodium chloride
equivalent (E value) of the other substance.
A solution contains 1.0g ephedrine sulfate in a
volume of 100 mL. What quantity of sodium
chloride must be added to make the solution
isotonic? How much dextrose would be
required for this purpose?
(E-value ephedrine sulfate=0.23)
(E-value dextrose=0.16)
V = W x Evalue x 111.1
Using the USP method for adjusting
isotonicity, compute for the required volume
to make 0.5 g of atropine sulfate (E=0.13)
isotonic.
V = 0.3 g x Evalue x 111.1
Theories of Acid & Bases
1. Arrhenius Theory
2. Bronsted Lowry Theory
3. Lewis Theory
is the negative logarithm of the H+
concentration
example: [H+] = 5x10-6; pH?
pH = -log(5x10-6) = 5.3
 Strong Acids:
 pH = -log [H+]

 Strong Bases:
 pOH = -log [OH-]
 pH = pKw – pOH

 Weak Acids:
 pH = -log (√Ka x Ca)

 Weak Bases:
 pOH = -log (√Kb x Cb)
 pH = pKw – pOH
Compute for the pH of a solution
containing 0.5 M boric acid with a Ka of
1x10-4 at 25°C.
What is the pH of 0.032 M ammonia
solution with Kb of 1.71x10-5.
are solutions that have the
property of resisting changes in
pH when acids or bases are
added to them
 [salt]
pH = pKa + log -----------------------
[weak acid]
[weak base]
pH = pKa + log -----------------------
[salt]
What is the pH of a buffer solution
prepared with 0.025 M ammonia
and 2.5x10-6 M ammonium
chloride? Kb = 1.71x10-5.
Compute for the molar ratio of
salt/weak acid required to prepare
a sodium acetate-acetic acid buffer
having a pH of 4.56. The Ka =
1.75x10-4
Compute for the % ionized of a
sodium acetate-acetic acid buffer
having a pH of 4.56. (Ka of acetic
acid is 1.75x10-4)
is the ability of a buffer solution
to resist changes in pH upon
addition of an acid/alkali
 occurs when pH = pKa

βmax = 0.576 C

C = total conc of buffer solution

What is the maximum buffer
capacity of an acetate buffer with a
total concentration of 0.020 mole
per liter?
Interfacial Tension (L-L only)
Surface Tension (S-L, L-G)
Surface Active Agents
lower the interfacial / surface
tension
Aka. amphiphile
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

Adsorption
 attraction on the surface
Cohesion
 attraction between similar molecules
Adhesion
 attraction between different
molecules
Wetting
 easy penetrability by a liquid
Capillarity
 rise of a liquid on a narrow tube
A system having a particle size
intermediate between true
solution and a coarse dispersion
 “Solvent-Loving”
 spontaneous form of dispersions
 thermodynamically stable
 Methods
1. HYDRATION
2. SOLVATION
 “solvent-hating”
 nonspontaneous
 thermodynamically unstable
 methods:
1. CONDENSATION (smaller to larger)
2. DEFLOCCULATION (larger to smaller)
3. PEPTIZATION (use of salting-out)
 aka: amphiphilic colloids
 characterized by having
hydrophilic and lipophilic regions
within the same molecule
1. Optical
2. Kinetic
3. Electric
 ability to scatter or
disperse light
 Brownian Motion
 random collisions of particles resulting to
irregular, zigzag path
 named after Robert Brown

 Diffusion
 spontaneous movement of particles from a
region of higher concentration to one of
lower concentration
 governed by Fick’s Law
Nernst Potential Zeta Potential
 aka:  aka:electrokinetic
electrothermodynamic potential
potential
 difference in potential
 difference in potential between the SURFACE
between the ACTUAL OF TIGHTLY BOUND
SURFACE OF THE LAYERS and the
PARTICLE and the electroneutral region
electroneutral region of of the dispersion
the dispersion
A system with particles being
larger than 0.5mcm
1. Coalescence
2. Creaming
3. Cracking
4. Phase
inversion
1. Agglomeration
2. Sedimentation
3. Caking
1. Syneresis
2. Swelling
3. Imbibition
4. Bleeding
 Greek terms: rheos “to flow” and
logos “study”
 scientific study of the
deformation and flow properties
of matter
 elasticity, fluidity, viscosity
measure of the resistance to flow
1.Absolute Viscosity
2.Kinematic Viscosity
3.Relative Viscosity
 F
η = ---------
G

F = shear stress
G = shear rate
units: Poise, centiPoise (cP)
 η
κ = ---------
ρ

η = absolute viscosity
ρ = density of the substance in g/cm3
units: Stoke, centiStoke (cS)
ratio of the viscosity of a solution
to the viscosity of the solvent

unitless
constant viscosity with increasing
rate
Shear
rate

Shear Stress
A. Shear-dependent Viscosity
1. Plastic
2. Pseudoplastic
3. Dilatant
A. Time-dependent Viscosity
1. Thixotropy
2. Rheopexy
flow begins only
after a yield
value is
exceeded
Shear Rate

yield value

Shear Stress
“shear-
thinning”
Shear Rate

Shear Stress
“shear-
thickening”
Shear Rate

Shear Stress
Thixotropy
 gel-sol transformation

Rheopexy
 sol-gel transformation
 characterized as having fixed
shapes
 nearly incompressible
 have strong intermolecular forces
 very little kinetic energy
 their atoms vibrate in fixed positions
have definite 1. cubic
geometric forms 2. tetragonal
with 6 common
crystalline 3. hexagonal
structures 4. rhombic
5. monoclinic
6. triclinic
aka: glasses or
supercooled
liquids
non-crystalline;
no definite order
have no definite
and sharp
melting points
 solids that have more than one
crystalline form
 have different physical
properties including different
melting points and solubilities
Enantiotropic
 change is reversible
Monotropic
 change is irreversible
Isotropic
 properties are identical in all directions
Anisotropic
 properties are different in all directions
study of small particles
1. Fundamental
 inherent in all individual particles
 eg. size, shape, density, volume

2. Derived
 combination of fundamental properties
 eg. bulk density, granule volume,
porosity
1. Optical Microscopy
2. Sieve Analysis
3. Sedimentation Method
4. Automatic Particle Counter
 use of a
microscope to
measure individual
particles
 adv: individual
particles can be
seen
 disadv: very
tedious, 2D-image
only
1. Ferret Diameter
2. Martin Diameter
3. Projected Area of the Circle
USP Method
sieve/mesh#
 number of
openings per
linear inch
disadv: attrition
of particles
 sedimentation rate or
free fall velocity of
particles
 apparatus: Andreasen
Apparatus / Pipet
 principle: Stokes’ Law
1. Coulter Counter
 principle: electric resistance

2. HIAC/Royco Instrument
 principle: light blockage

3. Gelman Counter
 principle: Faraday-Tyndall Effect
True / Particle Volume (Vp)
= volume of particle

Granule Volume (Vg)

= Vp + intraparticle spaces

Bulk Volume (Vb)

= Vg + interparticle spaces
True density = M / Vp

Granule density = M / Vg

Bulk density = M / Vb
Єinterspace = (Vb – Vg / Vb) x 100

Єintraspace = (Vg – Vp / Vg) x 100

Єtotal = (Vb – Vp / Vb) x 100

Given: volume of particle = 0.3 mL
intraparticle spaces = 0.1 mL
spaces b/w particles = 1.6 mL

Solve: Vg, Vb, Єinter, Єintra, Єtotal

Properties of Powders for
Granulation
1. Flowability
2. Compressibility
1. Angle of Repose
2. Carr’s Index
3. Hausner Ratio
Ө = arc tan h/r

Ө = arc tan 2h/d

A sample powder was made to flow
from a funnel suspended at a height
of 20 cm. A powder cone of 12 mm
from the surface was made as well
as a spread of 4 cm. Determine the
angle of repose.
A sample powder was poured
through a funnel and formed a cone
3.3 cm high and 9 cm in diameter.
What is the angle of repose?
 Vb - Vt
= --------------- x 100
Vb

Dt – Db
= ---------------- x 100
Dt
 Vb
= --------
Vt

Dt
= --------
Db
 A powder was poured in a graduated
cylinder and was noted to have a volume of
65 mL. It was allowed to compress by tapping
the cylinder on the table counter. The initial
volume was reduced by 15 mL. Determine
the Carr’s Index as well as the Hausner’s
Ratio of the powder.
represents the states of matter
that exist as temperature and
pressure are varied
heat necessary for 1 mole of a gas,
solid or liquid to change to another
phase
either gained or lost
NOTE: without latent heat, no
phase transition
solid to liquid (gained)
liquid to solid (lost)
liquid to gas (gained)
gas to liquid (lost)
solid to gas (gained)
gas to solid (lost)
used to determine the number of
independent variables (temp,
pressure, conc) that must be set in
order to define a system
F=C–P+2 (1-component system)
F=C–P+1 (2-component system)
F=C–P (3-component system)
 eg. water
 solid / liquid /gas
 solid-liquid / liquid-gas / solid-gas
 solid-liquid-gas
 aka: Condensed System

 system in which the vapor phase is ignored and

only the solid and/or liquid phases are
considered

 under normal condition of 1 atm

 Phase Rule: F = C – P + 1
 line from which a system separates into
phases of constant composition

 used to approximate the proportions of

components A & B existing at a particular
temperature
 aka: Ternary System

 temperature and pressure are both made

constant

 consists of 2 liquids that are partially miscible

to each other and a 3rd component or co-
solvent which has affinity to both immiscible
layers

 Phase Rule: F = C – P
is the study of the rates of reactions and
the mechanism by which these
reactions occur
application in pharmacy: stability and
bioavailability of pharmaceutical
products
 aka: degradation rate
 is the velocity with which the reaction occurs
 depends on:
 reactant concentration
 temperature
 pH
 presence of solvents or additives
 is the way in which the concentration of the
drug or reactant in a chemical reaction
affects the rate

 zero-order
 first-order
is the period of time required for the
amount or concentration of a drug to
decrease by one-half or 50%
Rate order Zero Order First Order
Reaction Rate Independent Dependent
Equation C = -k0t + C0 ln C = -kt + ln C0
Half-life 0.5 C0/k0 0.693/k
Unit C/t 1/t
is the period of time where 90% of the
original concentration is left and 10% is
already degraded
 0.1 C0
t90 = -----------
k0
 0.105
t90 = -----------
k
A suspension (125mg/mL) decays by
zero-order kinetics with a reaction rate
constant of 0.5 mg/mL/hr. What is the
concentration of the drug remaining
after 3 days?
The amount of drug remaining after 180
hr was 5 mg/mL from an initial
concentration of 60 mg/mL. Compute for
the first-order rate constant.
The concentration of drug remaining
after 2 hr was 9.60 mg/mL from an initial
concentration of 57.90 mg/mL. Compute
for the 1st order rate constant and half-
life of the drug.
An ophthalmic solution of a mydriatic
drug at 5 mg/mL exhibits 1st order
degradation with a k=0.0005/day. How
much will remain after 120 days?
Compute also for the half-life and shelf-
life.
If the half-life of a drug is 12 hours,
compute for the 1st-order rate constant.