PHYSICAL PHARMACY LECTURE

PRELIMINARY PERIOD

Content
Unit I Language of Physical Pharmacy

Fundamental concepts, measurable properties and fundamental units.

Density and specific gravity of solid and liquid.

Unit II Scientific Principles of Dosage Form Design

Solubility
Properties of Solution
Isotonic Solution
Rheology
Surface and interfacial phenomena
Dispersed systems
Kinetics and product stability

Unit III Pharmaceutical Preparation

Concept of Preformulation
o Physical properties of drug
o Drug and product stability
o Assay development
o Microscopy
o Powder flow properties
o Excipient Compatibility

Course Reference:
Basic Physical Pharmacy Ma, Joseph K. H. and Hadzija B.W. Jones and Bartlett
Learning,

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PHYSICAL OR THEORETICAL PHARMACY

Has been associated with the area of pharmacy that deals with quantitative
and theoretical principles of science as they apply to the practice of
pharmacy.
o Quantitative
numbers
o Qualitative properties
Use of senses
Physical properties
Aids the pharmacist in their attempt to predict the ff:
o Solubility
Solids - Soluble
Solubility Terms
o Very Soluble
o Freely Soluble
o Soluble
o Sparingly Soluble
o Slightly Soluble
o Very Slightly Soluble
o Practically Insoluble
Liquids Miscible
o Stability
Expiration date
Month Year (Jan 2016)
o The day is the last day of the month
o Compatibility
Physical incompatibility
Formation of PPT.
Chemical Incompatibility
PPT = new product
Therapeutic Incompatibility
Drug interactions
o Drug-Drug interaction
Synergistic Effect
Drug A + Drug B (1+1 = 3 effects)
Antagonistic Effect
Drug A + Drug B (1+1 = 0 effects)
o Rate of Absorption
o Duration of action of drug product
ER Extended Release
SR Slow Release
As a result of this , the pharmacist is in a better position to:
o Develop new drugs and dosage forms
o Improve upon the various modes of administration

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SIGNIFICANT FIGURES

All non-zero digits are significant (1-9)

Zeroes may or may not be significant
Zeroes between non-zero digits are significant
o 2.013 4 significant figures
o 12.3405 6 significant figures
For numbers that are less than 1, all zeroes to the right of the decimal point
after the non-zero digits are significant.
o 0.0010 2 significant figures
o 0.0345 3 significant figures
For numbers greater than 1, are zeroes to the right of the decimal point are
significant.
For large numbers that do not contain digits after the decimal point, the
terminal zeroes may or may not be significant
o 45000 express to scientific notation
4.5000X104 -5 sf
4.50X104 3 sf
4.5X104 2 sf
3010
3.01X103 3 sf
3.0X103 2 sf
1002
1.002X104 4 sf
1.0X104 2 sf

0.00050
5.0X10-4 2 sf
0.0002045
2.05X10-4 3 sf
2.045X10-5 4 sf
Addition/ Subtraction least number of decimal places
Multiplication/ Division least number of significant figures
o 1.005 + 9.01 = 10.015 10.02
o 200.0 + 4.560 = 204.560 204.6
o 750.0/3.0 = 250 2.5X102

-+--

Fundamental Dimensions
Dimension
Length

Symbol
L

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CGS unit
Cm

SI unit
M

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Mass
Time
Area
Volume
Density
Velocity
Acceleration
Force (m x a)

M
T
L2
L3
M.L-3
L.T
L.T-3
M L T-2

Pressure (F/A)

M L-1 T-2

Surface Tension
(F/L)
Energy (F x L)

M T-2

Density=

M subs
V subs

M L2 T-2

Density M H 2O
g
g
=
=
=
H 2O
V H 20 cm3 mL

cm
V
s
cm
Acc=
=
= 2
t
s
s
P=

G
S
Cm2
Cm3 =1cc =1mL
g/cm3
Cm/s
Cm/s2
Gcm/s2
dynes
g/cms2
dynes/cm2
g/s2
dynes/cm
G cm2/s2
Dynes . cm
ERG

F=m x a=g x

Velocity=

Kg
S
M2
M3
Kg/m3
m/s
m/s2
Kgm/s2
Newton (N)
Kg/ms2
N/m2
Kg/s2
N/m
Kgm2/s2
N.M
Joule

d cm
=
t s

cm
=DYNES
s2

F dynes
g
=
=
2
2
A
cm
cm s

F dynes g
Surface Tension= =
= 2
L
cm
s

Secondary unit of Pressure

1 atm =
=
=
=
=
=

760 mmHg
76 cmHg
1.01325 X 106 dynes/cm2
1.01325 X 105 N/m2
1.01325 bar
760 torr

Density

Ratio of the mass of a substance to the volume of the substance at the same
temperature

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Density=

M subs
V subs

2 Types:

Absolute
o When the mass is determined in vacuum
Apparent
o When mass is determined in air

H 2 SO 4=

M H 2 SO 4
V H 2 SO 4

Specific Gravity

Relative density
Ratio of mass of a substance to the mass of an equal volume of another
substance taken as standard
Standard
o Solid and liquid water
o Gases air, hydrogen

Specific Gravity substance=

mass of subs
spg of std liquid 1
mass equal vol of another substance ( STD )

25C/25C
o 25C std. temp for liquid except for alcohol
o 15.56C std. temp for alcohol
Ranges from 0.534 (Lithium Lightest Metal) to 22.48 (Osmium Heaviest
Metal)
Metric system (water)
o Density = sp. gr.
English system (water)
o Density = 62.4 lb/ft3
o Sp. Gr. = 1

Pycnometer Method

Leach Pycnometer

Flotation Method

Mohr-Westphal Balance
Hydrometer

Manometric Method

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Fischer-Davidson Gravitometer
o Affords a rapid method of determination
o Useful where only small samples of liquids are available
o

h1 d 1
=
h2 d 2

Pycnometer method

Leach Pycnometer
Most accurate
o Ex: Determination of sp gr of alcohol

sp gr alcohol=

wt of alc at 15.56
X1
wt of water at 15.56

1st Step: Weight of empty pyc

2nd Step: Weight of pyc + alcohol
3rd Step: Weight of pyc + H2O

sp gr alcohol=

wt of pycalcwt ofempty pyc

x1
wt of pyc H 2 Owt of empty pyc

Flotation Method
o Buoyant force effect upward force which any liquid exerts upon a
body placed in it.
o Archimedes principle
When a solid is placed in a liquid in which it is capable of
floating, it sinks to a depth where the body has displaced a
volume of liquid exactly equal to its own weight.
Mohr Westphal Balance
o Plummet (occupies a volume of about 5mL)
o Riders
5g = 0.x
.5g = 0.0x
0.05g = 0.00x
0.005 = 0.000x
Hydrometer
o Constant weight and variable depth of immersion
Baume hydrometer
Types
o For liquids heavier that water
o For liquid lighter than water
Twaddells, Becks, Sikes, Cartiers, Gay-Lussacs, Brixs
Alcoholmeter
Hydrometer with a thermometer

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Used to determine alcoholic strength of any liquid

containing alcohol and water only.
Tralles hydrometer
Tralles Hydrometer
A Variable weight and constant depth of immersion
Fahrenheit hydrometer
One of the first instruments of the variable weight,
constant depth class.
Lovis beads
Specific gravity beads
Useful in operations where boiling liquid is to be
evaporated until it has a given specific gravity.
Mixing liquid of different densities.
Nicholsons hydrometer
Can be used for taking the specific gravity of heavy or
light liquids

Specific Gravity Determination of Solids

Sinker method
Pycnometer method
o Specific gravity bottle
o Used for solid substances which are in small fragments of even in a
much finer state of subdivision.
o Wt of empty pyc
o Wt of pyc + std liq
o Wt of pyc + subs
o Wt of pyc + subs + std liq

Sp gr=

wt of subs
spg of std liquid1
wtof std liq displaced by subs

Wt of subs = wt of pyc & subs - wt of empty pyc

Wt of std liq displaced by subs = (wt of subs + wt of pyc and std liq) (wt of pyc w/ subs & std)
Graduated cylinder
Immersion of a solid in a transparent liquid of the same density
o
o

4 Types of Solid

Insoluble in & heavier than water

Soluble in & heavier than water

Insoluble in & lighter than water

Soluble in & lighter than water

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Hydrostatic Balance

Substance in immersed into the liquid with the aid of a weightless thread.
Sinker dense insoluble body

Case I Solid insoluble in and heavier than water

Specific Gravity substance=

mass of subs
spg of std liquid 1
mass equal vol of another substance ( STD )

Specific Gravity substance=

wt of subsair
spg of std liquid1
wt of subsairwt of subs liq

Loss of wt = wt in air wt in liquid

Loss of wt = WA - WL

Case II Solid insoluble in and lighter than water

1.

Specific Gravity substance=

WA
spg of std liquid1
loss of wt of subsliq

2.

Specific Gravity substance=

WA
( wt of sinkersubsairwt of sinkersubsliq ) ( wt of sinker airwt of sinke

Specific Gravity substance=

WA
spg of std liquid
( wt of sinkerair +wt of sinkerliq )wt of sinkersubs liquid

3.

Loss of wt of subs in std liq = loss of wt of subs and sinker in std liquid loss of wt of
sinker in std liq
Loss of wt of subs in std liq = [wt of subs in air + wt of sinker in std liquid] wt of
both in std liq

Graduated Cylinder

Direct measurement of the volume of the solid based on the volume it

displaces when immersed in a liquid.

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wt of solid
volof liq displaced

Specific Gravity substance=

Immersion of a solid in a transparent liquid of the same density

Used for small solids, with a low specific gravity and insoluble in the liquid.

Specific Volume

Specific Volume substance=

vol of a subs
vol of an equal wt of std

Solution

Homogenous dispersion of two or more substances in each other.

Most important solutions:
o Gases in liquids
o Liquid in liquids
o Solid in liquids
Increase in concentration = increase in saturation

Unsaturated Solution

A solution that contains the dissolved solute in a concentration below that

necessary for complete saturation at a definite temperature.

Saturated solutions

A solution that contains as much dissolved solute as the solvent can hold
when in contact with undissolved solute.

Supersaturated solutions

Contains more of the dissolved solute that it would usually contain at a

definite temperature, where undissolved solute is present.

Methods of expressing concentration

M=

n solute
L solution

m=

n solute
Kg solution

M=

wt of solute
MW L solution

m=

wt of solute
MW Kg solution

Osmolarity

OsM =

milliosmol solute
L solution

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OsM =

mmol i
L solution

OsM =

n 1000 i
L solution

Complete ionization Strong electron and weak electron

# of ions present
NaCl in H2O Na+ + Cli=2
NH4Cl NH4+ + Cli=2
n= wt/MW
Solutes

Non-electrolytes
o Substances that do not yield ions when dissolved in water
Example: Sucrose, Glucose, Naphthalene, Urea
Electrolytes
o Substance that form ions in solution
o Strong electrolytes: complete ionization
o Weak electrolytes: incomplete ionization
Normality

number of equivalentsof solute

L solution

N=

grams solute
eq wt solute
N=
L solution

N=

grams solute
mw
L solution
f

Eq Wt = MW/Factor
Factor
For acid number of replaceable H+
For bases number of replaceable OH For Salts total valence of either radical (+/-)

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HCl H+ + ClF=1
i=2
H2SO4 2H+ + SO4-2
F=2
i=3
NaCl Na+ + ClF = +1 + -1 = 0
F=1
i=2
BaCl2 Ba+2 + 2ClF = (1)(+2) + (2)(-1) = 0
F=2
i=3

NaOH Na+ + OHi=2

BaCl2 Ba+2 + 2Cli=3

w
grams solute
=
100
w grams of solution
Mole Fraction=

nsolute
total number of n solution

Mole Fraction solute=

nsolute
nsolute +nsolvent

Mole Fraction solvent=

nsolvent
nsolute +nsolvent

Mole Solute=mf solute 100

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Mole Solvent=mf solvent 100

mole solute+ mole solvent =100

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