MODULE 5│PHARM 3

PHYSICAL PHARMACY
PHYSICAL PHARMACY • responsible for the solubility of non-polar molecules
I w/ the • Ex. Iodine complex with salts /Formation
dide
quantitatives theoretical principles
competein
deals of

• Application of physical chemistry in pharmacy e

• Study of physiochemical properties of substances used in PHYSICAL PROPERTIES OF MATTER

drug formulation
Pharmaceutical sciences -

integration physical phar in

of the bio
aspecto f pharmacy Additive ~sum
FORCES OF ATTRACTION • depends on the total contribution of the atoms in the
-

molecules e n

INTRAMOLECULAR FORCES • Ex. MW, Mass

-
Bond Mpe EN diff
• ↑ atoms = ↑MW = ↑Mass
• Forces of attraction within the molecule
-
Pure covalent 20.4

Polar covalent0.4-1.7(2.0) Constitutive

Types: Ionic > 1.7(2.0) • depends on the & arrangement of the number & kind of atoms
-

within a molecule
- -

a. Ionic Bond Causes:metallic borderely moving e • Ex. Refractive Index, Optical Rotation
• Transfer of electrons between a non-metal & a metal
-

• observed in formation of salts Colligative

• &
function of the number of species or particles present in a
-

b. Covalent Bond given solution

• sharing
-
of electrons between two non-metals • Ex. Osmotic pressure elevation, Vapor Pressure lowering,
• observed in organic compounds Freezing Point Depression, Boiling Point Elevation
combined additive -

constitutive property -
molar refraction
-
-
-
INTERMOLECULAR FORCES TYPES OF PROPERTIES

• forces of attraction between molecules Intensive

&
• 0
independent of the amount of the substance in the system
-

Types: nOR:Largely governed by electron orbital interactions between molecules • Ex. Temperature, Pressure, Density, Viscosity, Surface
- - -
-

tension, Specific Gravity

-

a. Binding Forces
• Cohesion – similar molecules Extensive
• Adhesion – different molecules • depends on the quantity of substance in the system
-

• Repulsive – prevent molecules from annihilating each other • Ex. Mass, Length, Volume
-

for polarity:
Requirements
b. Attractive Forces 1) EN difference -
IEN diff:higher polarity
STATES OF MATTER
• Van der Waals -

dipole moment

• Hydrogen Bond 2) Symmetry

ofmolecule THE GASEOUS STATE
• Ion-Dipole
• Ion-induced Dipole Gas Laws
• refers to an ideal situation whereO-no intermolecular
I Van der Waals Forces interactions
-
exist and collisions are perfectly elastic
• weak forces that involve the dispersion of charge across a • there is no energy exchanged upon collision
-
-

molecule called a dipole

--

1. Boyle’s Law In P&

-

1. Keesom
6 Forces (orientation
⑧ effect) I 1-7 kcal/mole -
• relates ⑧ pressure Inverse:
volume and-
• Dipole-dipole • - constant temperature P,VI P2V2
&
=

• molecules are polar with permanent polar dipoles

-
-
• PV = k
• Ex. water, HCl, ethanol, acetone, phenol
1
2. Gay-Lussac and Charles’ Law Dr:VxT -

2. Debye 0
W Forces (induction effect) • states that theC
volume and absolute> temperature of a gas at
-

• Dipole-induced dipole
-
or 1-3 kcal/me
/polarization >constant pressure are directly proportional
• transient dipole induced by a permanent dipole • V = kT
=
•
E
polar molecules produce temporary electric dipole in
nonpolar molecules 3. Ideal Gas Law
• Ex. Ethyl acetate, methylene chloride, ether • PV = nRT
• R = 0.08205 liter.atm/mole.K or 8.314 joules/mole.K or 1.987
3. London Forces (dispersion effect) -> 0.5-1kcal/mole cal/mole deg avogadro's 4) direct:naV -

• Induced dipole- induced dipole • n = number of moles 0~and

orrelationship pil
• induce polarity between& non polar molecules =12
- V2
• responsible for liquefaction of gases Kinetic Molecular Theory
• Ex. Carbon disulfide, CCl2, hexane • Gases are composed of particles called atoms or molecules,
-
-

the total volume of which is so &

small as to be negligible in
esters,
2-8 Kcal/mole-mEx:H20, alcohol, 2.A, aldehydes
- -

2 Hydrogen Bond -

L capable H'bonding of
relation to the volume of the space in which the molecules
• electrostatic interaction of H with highly electronegative are confined
>
- -
atoms (S,
a N, Cl, F, O) Et • The particles of the gas do not attract one another, but
• accounts for unusual properties of water instead move with complete independence
• The particles exhibit continuous random motion owing to
4 Ion-Dipole Interaction ion polar molecule their kinetic energy
-
-

• polar molecules are attracted to either positive or negative • The molecules exhibit perfect elasticity

!
-
-

charges -

• occurs when salt is dissolved in a polar solvent

- -
THE LIQUID STATE
• solubility if crystalline substances in H2O
-
e
-
- -

• quaternary ammonium + tertiary amine Critical temperature

Ex:solubility salts
of in H20
• temperature above which a liquid can no longer exist
non-polar 2); ion
↳ Ion-Induced Dipole -or w/permanent c harges (t) or

• induced by close proximity of a charged ion to a non-polar

- -
molecule

Module 5 – Physical Pharmacy Page 1 of 7 RJAV 2022

3 types ofmolecular
Dipoles:(P, I, I)
1) PermanentDipoles
Recombination)
-
2 atoms w/ lfE
is ()
-
1 atom is (t); other
2) Instantaneous Dipoles r crusion)
-

occur due to dance in one place than other -

a
temporary
-

dibole
-
(congealing)

3) Induced Dipoles
quantmeatorbedrefaced
LatentHeat =

of by a substance
-

-I molecule molecule's
of
permanentdipoles requels another take
-
electron

Hydrogen bonding:
to responsible unusual 1 20:
O
-
-

for the prop. of

1) ⑧
high dielectric constant -

2) vapor
abnormally
- -
pressure
-
3) high boiling point
H-bonds can also intramolecularly:
exist
-

v in --
a heis e

proteins
-
B. sheets

-
acids
Mesophases aka Liquid Crystals

Bond Energies Cotate ofmatter

Properties of L.C:
-

Flow prop
-
-
⑧ -

Birefringent
w/ temp
-
-
exhibitcolor changes
-

sensitive to electric fields

-
anstropic
characteristics ofmolecules mesophases (mesogen)
4
that form

1) Rigid
... 2) Org molecules

3) possess dipole a
4) Elongated near in shape
Application:I
and
ofIMFA:stronger
strength interaction =

↑ BP, MP, viscosity, surface area, etc.

Types 1.2:
of

1) Lyotropic L.) -
result
from action
-
ofcertain solvents on solids

2) Thermotropic L.) -

results from heating solids

-

La
-

La
Ex: itraconazole, fenoprofen a/ca, ciclosporin,

cholestery, benzoate

- - -
-o - -
TYPeS:

States ofMatter

1) Gas

2) Liquid
i) solid -

4) Plasma-hiquestentropy
i) Bose Einstein condensate least ⑰
entropy
- -

matter:⑳
In physphar, 4th - -
state of Mesophase
Ex:Liquid crystals -
bet SBL

Supercritical Fluids -
bet IIE
state variables in Gas Low

-
-
-
-
- -
-
-

-
-
E
-

--

Pro
- - ~Gasnaw
=0.08205
as constant

L-atm/mol-k
i

8.314 Joules/mol-k
=

Earscanen
Lomws
volume

Basic Gas Laws

Ideal Gas Law

PV=nRT i n
w
=
 note:

↑
CP critical point
=

its critical temp

pressure read liquefy
to at
->
a gas
Pc critical
=

pressure
LSG exist
critical temp beyond who do
the not
temp
↑
2 = -

↳o used in: decaffeination

-

-chromatography ofpolar
drug
Critical Pressure Supercritical Fluids-
-
-Elimination of toxic
-

wastes

• pressure required to liquefy a gas a critical temperature • properties intermediate between those of liquids and gases
-
- -

highest vapor pressure of a liquid formed from the gaseous state where the gas is held under a
combination of temperatures and pressures thatE
-

exceed the
-

- -
-
Boiling Point critical point of a substance
-
• the temp at which the vapor pressure of the liquid equals the
external and atmospheric pressure THE PHASE RULE (GIBB’S PHASE RULE)

THE SOLID STATE • relates the effect of the least number of -independent -

variables (T, P & C) among the various phases (S, L & G)

• have fixed shapes
-
that can exist in an equilibrium system containing a given
• nearly incompressible
-
number of components 𝐹 =𝐶−𝑃+𝑋 -

• have strong intermolecular forces

-
Where: F = no. of degrees of freedom
• very little kinetic energy
- -
C = no. chemical components -

• atoms vibrate fixed positions about an equilibrium position, &

-
P = no. of phases
so there is very little transitional motion
-
X = variable dependent upon considerations of
-

the phase diagram -

(ept:
crustal) ⑧
Crystalline Solids -
anisotropic • F – least number of intensive/independent variables that
-

• Solids whose structural units are arranged in a fixed -

must be fixed to describe the system completely
-

-
geometric pattern or lattices -
• 0
C – smallest number of constituents by which the
-

• definite shape composition of each phase in the system at equilibrium can

-

• orderly arrangement of units ahenous be expressed in the form of a chemical formula or equation
-

- -
-
- -

• definite and sharp melting points

-
-
-
-
• P – number of homogenous physically distinct portion of a
• 6 Distinct Critical Systems Based on Symmetry system that is separated from other portions of the system by
• Cubic – Sodium Chloride bounding surfaces
• Tetragonal – Urea oforthorhombic (11) • 1 Phase – F=2 – Bivariant
Rwir
-

-
-
-

• Hexagonal – Iodoform -
• 2 Phases – F=1 – Univariant
• Monoclinic – Sucrose navir(1) (Sum • 3 Phases – F=0 – Invariant
-

-
I
-

• Rhombic & – I2 iodide

-

• Triclinic – Boric Acid eIrio

-
-
THERMODYNAMICS
so tropic
-
Amorphous Solids -a stabilized by polymer/ surfactants
-
• deals with the quantitative relationships of interconversion of
• glasses or supercooled liquids
- - -
-
-
the various forms of energy
• molecules are arranged in a random manner -
- heterogenous • System – a well-defined part of the universe under study
• no definite melting points
-

• Surroundings – the rest of the universe from which the

-

• -
faster dissolution rate observations are made
In terms solubility:amorphous Crystalline
of • Boundaries – physical or virtual barriers that separate a
Polymorphism system from the surroundings
• condition where substances can exist in more than 1
crystalline form TYPES OF SYSTEMS
-

• polymorphs have& different melting points, x-ray crystals and

diffraction patterns and solubility 1. Open – energy and matter can be exchanged with the
• Theobroma Oil Polymorphs (Melting Points) /theobroma cacao surroundings
• Unstable γ form → 18°C
• α form → 22°C
-

↳ minimum temp:c 2. Closed – energy can be exchange with the surroundings but
• β prime form → 28°C not
destroy the B form
to not matter
• Stable β form → .
.
-
34°C
-desirable form -

• Types of Polymorphism 3. Isolated – neither matter not energy can be exchanged with
• v Enantiotropic – reversible the surroundings
• ~ Monotropic – unidirectional transition metastable stable
-

cunstable)
Allotropy-special care ofpolymorph -

↳ex: diamond graphite

-
FIRST LAW OF THERMODYNAMICS
Freezing Point -

• temperature at which liquid → solid • Energy cannot be created nor destroyed, it can only be
• melting point of a pure crystalline compound transformed into a different form
• Adiabatic – constant heat
Latent Heat of Fusion • Isothermic – constant temperature
• Energy absorbed when 1g of a solid melt • Isochoric – constant volume
• Heat liberated when it freezes • Isobaric – constant pressure

LIQUID CRYSTALLINE STATE SECOND LAW OF THERMODYNAMICS

• liquid crystals → intermediate between liquid and solid states • Refers to the probability of the occurrence of a process
• may result from the heating of solids (thermotropic) or from based on the tendency of a system to approach a state of
the action of certain solvents on solids (lyotropic liquid energy equilibrium
crystals) • Entropy

Two Main Types of Liquid Crystals THIRD LAW OF THERMODYNAMICS

1. Smectic • The entropy of a pure crystalline substance is zero at

• Soap like or grease like absolute zero because the crystal arrangement must show
• molecules are mobile in 2 directions the greatest orderliness at this temperature
• rotates in 1 axis
CONDENSED SYSTEMS
2. Nematic
• threadlike • &
S & L phases only
-
• molecules are mobile in 3 directions • the vapor state is disregarded with an assumption of working
• rotates in 1 axis at a pressure at 1atm
-

F c P 1 = -
+

• Cholesteric – special type of nematic • 2 Components – liquid phases

-

2 Components –D
e
-

• -
S & L – eutectic mixtures -

• 3 Components
-

Module 5 – Physical Pharmacy Page 2 of 7 RJAV 2022

Gibb's Phase Rule Two component
system (M curve)
-

↳
One-componentsystem (Y curve) Eutectic mixtures -

w/SBL phases

!
-
- - -

00 -

For One phase area:S/2/G

F =
c -
P 2 +

1 2 (Bivariant)
=1 2
I
+ =

detect
-

-
incomp
For S-b/2-G/G-S Application:
adaempression
Phase
Boundary: reme cy:
-
-

F C P 2
= - +

=1 -
2
2 + 1
=

[Univariant)
-
-

V Intentional Entectic mixture

For Triple Point:S-L-G CEx:EMLA -
combi ofLidocaine & Pirilocaine
-
-

F
=

c
-
P 2 +

n ot
* all entectic mixtures are
incompatibility
(want)
-
-
1 0 Fixed unique
= 3 +
-
2 =
-
- -

two-componentsystem (C =2) - (U or curve ( Three-component system (C=3] (triangular)

-
&

↳Fermany
-

-
aredissencomponent -

TYPES OFCrystalline Solids

--
- -
-

-----
-
-

&
solvates aka
Meolymorphs

trapped
↳ occurs
in amarket
residual

-rates anhydrous renteare

when
-

-
↳ Ex:B-lactums:
Ampicillin Ma.3 H20

Lacyamiss
0 to
prone sis
to

amorphous solids aka liquids

red
lo-molecules arranged in a random manner

-tend flow
to

-
more soluble than crystalline
-
No definite MPDX-ray diffraction pattern

I
⑧ -
-

⑧ -
 TWO COMPONENT SYSTEM CONTAINING TWO LIQUIDS • Bulk Volume – total volume of the material
-

• Void Volume – difference between 00

-
bulk and true volume
Binodal Curve
• area within the curve which represent a 2-phase system Density
• True Density – density of actual particle -> determined by betometer
-

Upper Consulate/Critical Solution Temperature • Granule Density – volume of particles together with
-

• maximum temperature at which two phase region in the intraparticulate spaces by displacement
were
-

phase diagram of a two-component system containing two • Bulk Density

-

liquids will exist • mass of powder divided by the bulk volume - by t

density
- -
apparate
• D USP Method 1 – Graduated Cylinder
Tie line • * USP Method 2 – Scott Volumeter
• line from which a system separates into phases of constant • A USP Method 3 –⑮ .Vessel
Sainless steel vessel method
composition ⑧ Tapped Density -

using a mechanical tapping device

• approximates proportion of components in a particular Flow Properties

temperature
Conjugate Phases • Angle of Response – maximum angle possible between the
• phases of constant composition that separate when a surface of a pile of power and the horizontal plane
mixture is prepared within the boundary of the 2-phase ℎ
system 𝑡𝑎𝑛𝜃 =
𝑟
Where: h = height of cone
TWO COMPONENT SYSTEM CONTAINING SOLID AND LIQUID r = radius of base cone
• ↑ AOR = ↑ Flow Property
Eutectic Point • Tapped Density – measured using a tapped density tester
• minimum temp. where both
-
- exist in liquid form by repeated tapping until a consistent tapped volume is
• point where solid A, solid B & the liquid phase co-exist achieved

THREE COMPONENT SYSTEM LIQUIDS

• Ternary system • less kinetic energy than gases

• 2 liquids that are miscible + 3rd component (co-solvent) with • occupy definite volume
affinity to both layers • take the shape of containers
• has 4 degrees of freedom • denser than gases
• not compressible
MICROMERITICS
SOLUTIONS OF ELECTROLYTES & NON-ELECTROLYTES
• study of small particles
-
-
True Solutions
Fundamental properties • molecular dispersions
• defined individually • particle size = <1nm
• Ex. particle size & shape, particle size distribution, surface
area Electrolytes
-

• form ions in solution

e n

Derived properties • electrical conductance

• computed • Strong Electrolytes
• dependent on fundamental properties • completely ionized in solution
• Ex. Porosity, Density, Flow properties, Packing arrangement • NaCl, HCl, H2SO4
Tt viaa • Weak Electrolytes
PARTICLE SIZE DETERMINATION • partial ionization
• CH3COOH and most drugs
&
Optical Microscopy method
Amirable
• microscope Non-Electrolytes
• individual particles can be seen • do not form ions in solution
• tedious and 2D image is only seen • no electrical conductance
• Ferret Diameter – measure of the distance between • sucrose, glycerin, urea

S I
tangents parallel to some fixed directions
y ways Projected Area Diameter – diameter of a⑧
-

• circle with the COLLIGATIVE PROPERTY

measuring
-

of same area of the particle

diameter • Martin Diameter – length of the line that bisects the particle
= ⑧
C Vapor Pressure Lowering
• pressure of saturated vapor above a liquid → escape of
O
Sieving
• use of sieves •
liquid
molecules
• official method – USP Method • nonvolatile solute + volatile solvent → decreased escape
• mesh number refers to number of openings per inch tendency
• A ↑ Mesh Number = ↓ Particle Size (inverse proportionality)
-
• vapor pressure is lowered proportional to relative number of
y uare openingthe added solutes
* Sedimentation • Ex. Dextrose + Water → ↓VP of water
• Andreasen apparatus
-

• A ↑ Sedimentation rate = ↑ Particle size (direct proportionality) Boiling Point Elevation

• follow the-Stoke’s Law I important relationships: (S, D,VL
-

Size/ diameter:id=BV-ovelocity
• temperature where VP of liquid = external atmospheric
1) pressure
-
Particle Size Determination 2) density: I density:*V • ↑ non-volatile solute in solution = ↑ BP of solution
3) viscosity (1):4visc BV

S·
• Coulter Counter Principle:Electric resistance
=

librage
-

REins Freezing Point Depression

A

• HIAC/Royco Pri:
-
-
amt of

• Gelman Counter
-
• Melting or Freezing Point
surface Ara -1) Arption-PAds, BSA2)
-
Air permeability resistance to
-
flow b SA • temperature at which S & L phases are at equilibrium
DERIVED PROPERTIES under1 atm
• indicator of purity
Porosity of Voids • Solutions have ↓ FPD than pure substances

•
⑧
Porosity – measure of a void volume in a powder material
-
-

Module 5 – Physical Pharmacy Page 3 of 7 RJAV 2022

Particle volumes Dispersed systems

1) (Vp)=ala particle volume

solutenase
Dispersedphaseaninternalphase
True volume
- -

Lo vol exclusive
of
-
voids
of
(unt/vei e)
2)
- -

Granule volume (Vg) N+particle

=
spaces

3) Bulk volume (Vb):1g Enearticle spaces

+ Classification based on particle size

=Up inter
intract+

-- - -
↳olume

Bulkiness / Specific
-

aka Bulk bulk volume - - -

preciprocal of density
-
-

-
- -

of
power the
- -

povosity
Classification Colloidal Systems
of (according Amatier)
to
-

- -
-

-
-
⑧ -

-
-
- -
-

-
-

- -

--
-
-
-
-
-

-
- -

Types ofColloidal SO'S

> - 0-
- 0
C
OE
-

- -
-

>
-
-
- -
-
- - - -

- - - -
-

Properties ofcolloids
1) Optical Property
↳ Faraday-Myndall Effect to
light-scattering
-

2) Kinetic Property (movement)

Diffusion, osms in

as the induced.Brownianmotion,
ally
2) are
externally:Viscosity
3) Electric property predicting stability oflip Solutions & Solubility
used for

a)Zeta potential/Electrokinetic
-
Potential -
Ex: Electrophoresis
-

b)hevst
or Electrothermodynamic potential -
cone, diff !
- -

the Electrical
e

Double layer
Gouy-Chapman-Stern Model of

auev:ernherMountries
- SUROn-rate limiting -

step
Lo hoves
-

whitney Equation
-

-
-
↳o measure ofthe electrostatic repulsive forces bet particles
↳↑ 2.P
B
= stable:deflocculated

USP solubility
Expression

-
-
-

u la For solubility
drug:ISA by particle size reduction =

-
dissolution:I BA
*

- -

USP Dissolution testing

solubility -

cone ofsolute
-
dissolved in a sent

Solubility Expressions: . . .

is solubility (me) rotating

⑧ t
basket
2) Molar solubility (s):M n/2
=
m =

3) USPsolubility
Expression -
-

Paddle
4) Product Constant(ISP) -

to desc.
solubility slig soluble electrolytes

city
of

G
-

Ay
L
Ex:AGCI

for recip -

k3p (s)(S) =
=

s -

= Ysp modified DF cylinder

ion prod> KSp:super stat
-
- -

KSP Sat
=
11 ~

unsaturated.
flow-through
11
< kSp =
o il -

ca + 2C-
caCk =
- - -

S
S 25
paddle over
For disk
ksp (s) '(2s)
= S(4s):49
=

transdermal

S:
3 Das - - -

rotating -
der
cylin

Factors affecting solubility Recip

-

dives le
=
1) nature of solute of solvent - "like
-
holder

2) temperature
↳a said Lip:Hermic
-
↑
s eubility
Eept:Exothermic
-
-
T, solubility

-
Gases:
*T, mility
Pressure
3) -

-
for gases:IP, *mility (sLaw)
a) concentration

5) Particle size IS.A-BP.S SISA, I

solubility

6) viscosity -

more viscous, less soluble

7) Presence salts
of
-
saltingin yout ;A,AMPR

8) pH-acidic drugs mnized (less soluble)and

-
Colligative Properties 3) Freezing pointDepression (ATf)

-
DT+ T F°
=
-
TfcsoIn)

↳.
-
-

are
- -

-
-

-
- m molality
n
=

17 molal FP constant
-
=

H20 1.86°/m=

-
-
=>

-
-
Final Freezing Point:
-

on)*_
-

Ttef
-
-

D Vapor Pressure Lowering (BP)

pressure linitial en

C
~orig inal

s
&
I
up covering 1 Psoln
-

Osmotic Pressure
Raould's Law:Psolh =X solventPo

Absolute
note: 9 thin a
Osmosis
-

movemento f Izo molecules from -

to

semi-permeable membrane

#
s olute
x po consecantes the solute cone. (conservate

DATAmRt -
van't Hoff ep-

mole fractor comp

->
where: **
in =
molarity
-
("/ sin)
R molar =

gas constant

T temp K
=

in

modification using molality

(m):

I MRT
=
-
Morse Equation
-

Properties Electrolyte solutions

Colligative of

2) Boiling PointElevation (DTb)

Ab ison)
E
Th -

- I
I
Final BR initial b

-
IATb
-
Mkb;
=
Where M =

-
(n/kg)
Molality
kb Molal BP constant
=

for 120:8.5100/m
-

Final BP:
Tb
DT
Tb sob
=
+

mik

C
Osmotic Pressure Buffer Capacity
• pressure required to prevent the movement of water through • buffer efficiency or buffer index
a semipermeable membrane from region of high to low ∆𝛽
concentration 𝛽=
∆𝑝𝐻
∆B = represents the small increment in gram equivalents per liter of
TONICITY OF SOLUTIONS strong base or acid added to the buffer solution to produce a change
in pH
Isotonic Solutions
• living cell does not gain or loss water SOLUBILITY
• same osmotic pressure with body fluids
• 0.9% NaCl solution, normal saline, D5W
-
• concentration of a saturated solution in which the dissolved
• solute is in equilibrium with its solid phase at constant
Hypertonic Solutions • Intrinsic Solubility
• more solutes compared to cell concentrations • Apparent Solubility

Eshrinking
• freeze lower than -0.52°C • Kinetic Solubility
• causes- crenation of the cell • Thermodynamic Solubility
• 5% NaCl solution
- -
Factors Affecting Solubility
Hypotonic Solutions -
D5W • Dissolution Rate of Solute
• less solutes compared to cell concentrations • Temperature
• freeze ② higher than -0.52°C • Addition of Salt
• causes lysis of the cell • Complex Formation
• distilled water
-
• Salt Formation
• Amorphous Form
Methods of Adjusting Tonicity and pH
1) Dmethod -

freezing pointdepression/aroscopic Descriptive Term Parts of Solvent for One Part of Solute
~ - -

Class I Methods 2) Emethod hall equiv method

-

-
Very soluble <1
• NaCl or some other substance is added to the solution of the
- -
Freely Soluble 1-10
drug to make it isotonic Soluble 10-30
Sparingly Soluble 30-100
Freezing Point Depression/Crysoscopic Method Slightly Soluble 100-1000
• FPD used to calculate the amount of solute to add in making
an isotonic solution INTERFACIAL PHENOMENON

Class II Methods • attributed to the effect of the properties of molecules located

• e water is added to the drug → isotonic solutions or close to the boundary between immiscible phases
• White Vincent Method – V = w x E x 111.1
- -
• Interface – boundary between 2 distinct phases
• Sprowls Method – V = 0.3g x E x 111.1
-
Surface & Interfacial Tension
-

THEORIES OF ACIDS AND BASES

Surface Tension
Theory Acid Base • force that pulls molecules of the interface together &
contracts the surface
Arrhenius Liberates H2O in aq.
-
Liberates OH in
solutions aq.
-

solutions Interface Tension

Bronsted-Lowry Proton donor Proton acceptor • force per unit length existing at the interface
- -

• between 2 immiscible liquids

Lewis Electron acceptor Electron donor
-
-
WETTING PHENOMENON
CLASSIFICATION OF SOLVENTS
• contact angle that a droplet of the liquid makes with the solid
• Photophilic (Basic Solvents) – capable of accepting protons • surface at the point of contact
from solute • ↑ Contact Angle θ = ↓ wetting
• Proteogenic (Acidic Solvents) – proton donating • 180° = complete non-wetting
• Aprotic – neither accepts nor donates
SURFACTANTS (SURFACE ACTIVE AGENTS)
Ionization of Weak Acids & Bases
• long chain molecules
• Ionization – complete separation of ions in a crystal lattice • affinity for both polar and non-polar solvents
when a salt is dissolved • reduces interfacial tension
• Dissociation – separation of ions in solution when the ions • based on Hydrophile –Lipophile Balance (HLB) Values
are associated by interionic attraction
Type Description Examples
Henderson-Hasselbalch Equation Anionic Long chain molecules of Sodium lauryl sulfate
• aka pH or buffer equation carboxylates, sulfates or
sulfonates
• preparation of drug solutions at a desired pH using both the
neutral and the salt forms of a drug Cationic Interactions with negatively Benzalkonium chloride
charged surfaces such as cell
• determine percentage of neutral and ionized forms at a given membranes; cytotoxic –
pH antimicrobial preservatives
• determination of pKa of an acid or a base Amphoteric Naturally occurring surfactants Polypeptides, Proteins
𝑠𝑎𝑙𝑡
Weak acids 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔 Zwitterions Alkyl pentanes
𝑎𝑐𝑖𝑑
Lecithin, Cephalins
𝑏𝑎𝑠𝑒 Non-Ionic Long but contains a small Fatty alcohols (lauryl,
Weak bases 𝑝𝐻 = 𝑝𝐾𝑏 + 𝑙𝑜𝑔 alcohol base (e.g., propylene acetyl, stearyl) Steroid
𝑠𝑎𝑙𝑡
glycol), sorbitol or glycerol to alcohols
BUFFERS which fatty acids are attached Glyceryl esters
to form fatty acid esters
• compound or a mixture of compounds which has the ability
to resist changes in pH when small amounts of acids and
bases are added

Module 5 – Physical Pharmacy Page 4 of 7 RJAV 2022

Method 1-A: cryoscopic/Freezingpointmethod Class 11 method
La involves determination volume
of H20
of
0.9% w/ nacl
reference solution:

tire freezing pointo fan isotonic 0

soln: -0.52 A. White Vincentm ethod

Ustr WxEx1I1.1;WxE:gNaCl x
=
=

ifmultiple components:

VH20=(WIXE, +Wax2..) x III. I

method
B. Sprow's
↳simplification
ofa 1%. one
-
solution.
of

fl.02
We method, wherein of
it dog is
led at
~ U-= Ex III. I
value
0.39 &
↳
U value -
m) of needed
the g
of the drug

Example:

Acid-Base Equilibria

PH concept Antoionization of 120

P = -10g[H] H20+ H20 Hu0+OH-

kW:CH0] (OHt] 1 x10 14

-
=

method IB:Sodium chloride Equivalentmethod

pOH=-109 (OH'
P1 40H 14(p(2n)
+
=

nacl ep. (Evalue) MaCI=1g weak bases

dug
a m t- o f &
the
of
Ionization weak acids
=

of

methods of obtaining E-value:

acid dissociation constant:
1) Liso method

E value 17x
=

any
*Lico:
idmg x k= (1.86)

2)
mw?Ivalue
at
met

wan"x
e

m w drug
note:mw nacl-58.5;i-1.8

①
Ex:Whatis the pH 0.1m HC1?
②
of What
is the pH of 0.1M
PH =
-109 [H+) CISCOUH? Ka 1.8x10-5
=

soi
ijg -10gx
I

pH tHAS
=

=-log
x 0.

7787
steps in tonicity (Emethod)
adjusting to

E
Buffers -

solns, thatresistputchanges

- -

- -

PH3 pKa:ionized -
is predominant
-

PH PKG:equal
=
ratio ionized
of a unionized
-

pHpKa:Unionized is predominant

Butter Capacity (B) itude resistance

the
of pH changes
to

-
-e
 HLB Values Utilities Examples INSTABILITY OF COARSE DISPERSION
1-3 Antifoaming agent Mineral Oil
Fatty Alcohol Emulsions
Wax • Creaming – upward movement of internal phase
3-6 W/O Emulsifying Agents Span 80
• Sedimentation – downward movement of internal phase
Lanolin • Flocculation – reversible aggregation of droplets
7-9 Wetting & Spreading Agents Brij 30 • Coalescence/Cracking/Breaking – complete fusion of
Docusate sodium droplets (irreversible)
• Inversion – change in the type of emulsion (W/O → O/W or
8-18 O/W Emulsifying Agents Twean 20 O/W → W/O)
Cremophor A25
13-16 Detergents Alkyl Benzenes Suspension
Sulfonates
• Caking – compaction of suspended particles at the bottom of
15-20 Solubilizing Sodium Lauryl Sulfate
the container
ELECTRIC PROPERTIES OF INTERFACES Gels, Jellies, Suppositories & Ointments
• Syneresis – shirking of gel structure caused by loss of liquid
• Nernst Potential – Electro thermodynamic
• Bleeding – liberation of liquid from the base
• Zeta Potential – Electrokinetic • Swelling/Imbibition – absorption of liquid into the structure
• Swelling – increase in volume
COLLOIDAL DISPERSIONS
• Imbibition – no increase in volume
Lyophilic
• Solvent loving -
RHEOLOGY
Elasticity stickiness
• dispersed phase consists generally or large organic
=

•
study of the flow of liquids fluidity (O(
molecules lying within a colloidal range
-

•
viscosity is the expression of the resistance of a fluid to flow

-
• Molecules of the dispersed phase are solvated – they are -
𝐹
-

-
associated with the molecule comprising the dispersion 𝜂=
medium 𝐺
• Spontaneously disperse to form colloidal dispersion
0F = shearing stress (dyne/cm2) – amount of force per unit area
-

required to cause a liquid to flow

• thermodynamically stable
OG = rate of shear (rev/min) – velocity of the system that leads to
-
the deformation of the liquid
Association -

• Amphiphilic VISCOSITY
• dispersed phase consists of micelles or small organic
molecules or ions whose size individually is below the Units of Measurement
colloidal range • Absolute viscosity –- centipoise/poise
• Hydrophilic or lipophilic portion is solvated – depending on • Kinematic viscosity –- centistoke/stoke
whether the dispersion medium is aq. or non aq. • Relative viscosity –C unitless
• colloidal aggregates are formed spontaneously when the Measurement of Viscosity
concentration of the amphiphile exceeds critical micelle • Capillary Tube Viscometers
concentration • measure the time required for a given volume of liquid
to flow through a capillary
Lyophobic • ↑ Time = ↓ Viscosity
• solvent hating • Ex. Ostwald & Ubbelohde viscometers
• dispersed phase consists of materials that have little • Follows Poiseuille’s Law:
attraction for the dispersion medium 𝜋𝑟 4 𝑡∆𝑃
• material does not spontaneously form a dispersion 𝜂=
8𝑙𝑣
• r = radius of capillary
PROPERTIES OF COLLOIDS
• t = time to flow
• P = pressure in dyne/cm2
Kinetic Properties
• l = length of capillary
• Brownian Movement – particles appear as tiny points of
• v = volume of liquid flowing
light in constant motion
• Diffusion – movement of particles from high to low
• Rotational Viscometers
concentration until equilibrium is achieved
• makes use of a bob or spindle w/c is immersed in the in
the liquid whose viscosity is to be determined
Optical Property
• Rotating Bob – Brookfield, Rotovisco, Stormer
• Tyndall Effect – ability to scatter or disperse light
• Rotating Cup – McMichael
• Faraday Effect
Factors Affecting Viscosity
Electrokinetic Effect
• Temperature
• Electrophoresis – movement of a charged particle through
• ↑T = ↓viscosity in liquids; ↑ in gases
a liquid
• Shear Rate
• Electroosmosis – movement of a liquid through plug or
• Time
membrane across which a potential is applied
• Concentration of Solution
• Sedimentation – creation of a potential when particles
undergo sedimentation
NEWTONIAN SYSTEMS
• Streaming potential -- potential created by forcing a liquid
to flow through a plug or bed of particles
• direct relationship between shearing stress & rate
- -

• constant viscosity with increasing rate

COARSE DISPERSION - -

• E.g., water, ethanol, acetone, glycerin, benzene

• Emulsion
NON-NEWTONIAN SYSTEMS
• Suspensions
• Semisolid preparations – gels, jellies, suppositories &
a. Plastic Flow
ointments
• Bingham bodies
• curve does not pass through the origin but rather intersects
the shearing stress axis at a particular point (yield value)

Module 5 – Physical Pharmacy Page 5 of 7 RJAV 2022

 Time -

dependent

Newtonian Flow inixotropy

-constantviscosit

F is proportional G
to -

-
F/A
--
note:F-shear stress -

G-shear
-
rate -

ar/dr

Rheopexy

-
-
-

non-Newtonian Flow - - -

to change in viscosity increasing

with shear rate -

- -

- -

-
- Luyaluronic
acid

- -

time-independent
Plastic Flow -exhibited by Bingham bodies
Instruments:Viscometers
-

-
C
-
-

>
-

-
---
Pseudo plastic Flow -
-

viscosity
-

↳8 shear imming systems Vbw/I Determination newtonian

of

- -

pP19h
=

DilatantFlow
Lo shear-thickening systems
-

Lo viscosity &W/
-
rats shear
of
 • a yield value must be overcome before the system begins to By manipulation of the equation, it can be used to determine the
flow following
• Ex. Flocculated suspension, gels, ointments, pastes, • Pressure
surfactants, polymeric substances • Volume
• Temperature
b. Pseudoplastic Flow
•
•
shear thinning systems
curve begins at the origin
•
•
•
No. of moles
Weight
Molecular weight
W
• no yield values • Density
• viscosity decrease w/ increasing shear rate 𝑤𝑡 𝑃𝑉(𝑀𝑊)
𝑛= 𝑤𝑡 =
• Ex. Polymer solution, Na alginate, Perityl cellulose, PEG 𝑀𝑊 𝑅𝑇
𝑤𝑡 (𝑤𝑡)𝑅𝑇
𝑃𝑉 = ( ) 𝑅𝑇 𝑀𝑊 =
c. Dilatant Flow 𝑀𝑊 𝑃𝑉
𝑤𝑡 𝑃(𝑀𝑊)
• shear thickening systems 𝐷= 𝐷=
𝑉 𝑅𝑇
• reverse effects of pseudoplastic flow
• viscosity increases with increases shear rate
Real Gas Equation
• Ex. starch in H2O, conc. suspension of inorganic pigments in
H2O, Zinc Oxide, Barium sulfate or Titanium oxide in H2O
Van der Waal Equation for Real Gases

!
𝑎𝑛2
Thixotropy (𝑃 + ) (𝑉 − 𝑛𝑏) = 𝑛𝑅𝑇
• decrease in viscosity with time when flow is applied to a 𝑉2
sample previously at rest and the recovery of viscosity in
Where:
time when flow is continued
a/V2 = internal pressure due to IMFA
• Ex. aq. bentonite magma
b = excluded volume
→ accounts for the incompressibility of the gas
Rheopexy
• refers to the phenomenon that the gel formation of a system
NOTE :+ in
A Ideal Gas: ↓P, ↑T Partial Pressure Marctions
may be facilitated by tapping or low shear compared to
-

* Real (Non-Ideal) Gas: ↑P, ↓T PA:XaPT;mole fraction (xi):

.
keeping the sample at rest
-

Xa At
=
nic solute)

• time dependent increase in viscosity during flow

-

• Ex. Bovine synovial fluid, serum albumin due to protein, 1 mole of ideal gas
Sodium hyaluronate
-
-

𝑃𝑉 = 𝑛𝑅𝑇
Antithixotropy 𝑃𝑉
• time dependent increase in viscosity during flow caused by
reversible aggregation of particles
-
𝑛=
𝑅𝑇
= 1.0

• reversed hysteresis loop Dalton’s Law of Partial Pressure

• Ex. magnesia magma
The total pressure of the system,I
(PT) is the sum of the individual
GASES
-

partial pressure of each component

-

• have kinetic energy that produces rapid motion VAPOR PRESSURE OF SOLUTION
• held together by weak intermolecular forces
•
•
capable of filling all available spaces
easily compressible
-
Vapor Pressure
• A measure of escape
-
-

Raoult’s Law e n

GAS LAWS
In&
ideal solution:
• refers to an ideal situation where no intermolecular
• The partial VP of each volatile constituent is equal to the VP
interactions exist and collisions are perfectly elastic
-
-

of the pure constituent multiplied by its more fraction in the

-

• there is no energy exchanged upon collision

solution
Boyle’s Law Gay-Lussac and
Charles’ Law
Avogadro’s S
> PA = PA°(XA)
PB = PB°(XB)
Where: P = partial vapor pressure of -solute
P and V relationship V and T relationship V and n relationship -

P° = vapor pressure ofE

-

pure solute
-

(Constant T, n) (Constant P, n) (Constant P, T) -

-
-

#A+
Inverse: P ∝ 1/V Direct: V ∝ T Direct: n ∝ V
Prs
𝑷𝟏𝑽𝟏 = 𝑷𝟐𝑽𝟐 𝑉1 𝑉2 𝑛1 𝑛2 Graham’s Law
= =
𝑇1 𝑇2 𝑉1 𝑉2 ~ Itobconc. -
* movementt hin a small
opening
Graham’s Law of Diffusion and Effusion
Combined Gas Law •
-

The speed of diffusion of a gas is relative to the MW or

- -

density of the gas

-

&
-

𝑃1𝑉1 𝑃2𝑉2 1 1
= 𝑟𝑎𝑡𝑒 ∝ 𝑟𝑎𝑡𝑒 ∝
𝑇1 𝑇2 √𝑀𝑊 √𝑑𝑒𝑛𝑠𝑖𝑡𝑦
NOTE: Gay-Lussac’s Law also related to P and T relationship
(Amonton’s Law)
𝑃1 𝑃2
=
𝑇1 𝑇2
&) ) 𝑓1 √𝑀𝑊2
𝑓2
=
𝑀𝑊1 compare
to the rate aes
of

-
Henry’s Law
Ideal Gas Laws

Ideal Gas Equation

• Equation of state of an ideal gas (theoretical gas behaving
ideally)
↳ •

C
C=kP
Where:
-
The solubility
--
W↑P = higher solubility
-

~ C = Concentration of gas in solution

⑦
of gas is directly proportional to pressure at
constant temperature

• PV = nRT w P = pressure
=

Module 5 – Physical Pharmacy Page 6 of 7 RJAV 2022

 VAPOR PRESSURE-TEMPERATURE VARIATION

Clausius-Clapeyron Equation
• The relationship between the vapor pressure and the
absolute temperature of a liquid
𝑃2 ∆𝐻𝑣𝑎𝑝 (𝑇2 − 𝑇1)
log =
𝑃1 2.303𝑅𝑇1𝑇2

Where P1 = initial vapor pressure

P2 = final vapor pressure
T1 = initial temperature in K
T2 = final temperature in K
R = gas constant (8.314 J/mol-K
NOTE: the molar heat of vaporization (∆Hvap) is the energy required
to vaporize one mole of a liquid

DRUG PRODUCT STABILITY

• extent to which a preparation retains the same properties

that
• it had at the time of formulation
• It is concerned with:
• Physical Properties
• Chemical Properties and Composition
• Microbiological Sterility
• Therapeutic Activity

Photodegradation
• sensitivity of drug to UV light
• prevention → light resistant / opaque containers

Hydrolysis & Acid-Base Catalysis

• degradation of esters, amides, lactams to carboxylic acid

CHEMICAL KINETICS
-
REACTION RATES
P
• may refer to the rate of degradation or formation of a product
from a given reaction
• velocity with which the reaction occurs
• Influenced by:
• Concentration
• Temperature
• Change in pH
• Presence of additives -

•
•
Presence of solvents
Radiation O =
• Catalytic Agents or Enzymes

ORDER OF REACTIONS
->
Zero Order amount
dissolved
-I
e n conc. susp
of

• concentration independent kinetics

-

• elimination of a reactant will be linear with time

• Ex. suspension

First Order -
- kt
Ct C0 e
=

-
• concentration dependent reaction
-

• rate of reaction is proportional to the first power of the

concentration of a single reacting species
• most drugs follow such order of reaction

Second Order
• amount of drug is decreasing at a rate proportional to the
square of the amount of drug remaining
temperature & Reaction Rate

• uncommon
E

Module 5 – Physical Pharmacy Page 7 of 7 RJAV 2022