Physical Pharmacy Lecture Notes

Dr Prakash Katakam
Faculty of Pharmacy, 7th April University, Zawia, Libya
MATHEMATICAL PREPAPRATION
Dimensions and Units
Dimension = Measurable quantity
The Properties of matter are usually expressed by the use of three fundamental
dimensions: Length, Mass and Time.
Each of these properties is assigned a definite unit. A reference standard is a

fundamental unit relating each measurable quantity to some natural or artificial
constant in the universe.
Table: Fundamental Dimensions and Units:
Dimension Symbol CGS unit SI unit

Length L Centimeter (cm) Meter (m)
Mass M Gram (g) Kilogram (kg)
Time T Second (s) Second (s)
• Dimension = Measurable quantity

• Unit = Standard quantity
Derived Dimensions and Units

Dimensions such as area, density, pressure and energy are compounded from
the three fundamental dimensions just referred.
Derived Dimensional CGS unit SI unit

Dimensions Symbol
Area (A) L2 cm2 m2
Volume (V) L3 cm3 m3
Density (e) ML-3 g/cm3 kg/m3
Velocity (v) LT-1 cm/sec m/s
Acceleration (a) LT-2 cm/sec2 m/s2
Force (f) MLT-2 g.cm/sec2 kg.m/s2
Dyne Newton = N
PHYSICAL PHARMACY, 1 I Year B. Pharmacy

Dr Prakash Katakam
Statistical Analysis of Errors
Errors may be defined as a deviation from the absolute value.
Mean Error: The difference between the simple arithmetic mean and the true
value gives mean error.
Relative error: The relative error is obtained by dividing the mean error by the
true value.
Arithmetic Mean: The Arithmetic mean X is obtained by adding together the

results of the various measurements and dividing the total by the number N of
the measurements.
Arithmetic mean = X = ∑X i
N
X = arithmetic mean (average)
Σ = (Sigma) = the Sum of
Xi = individual measurement
N = number of measurements
Mean Error = Simple arithmetic mean – True Value
Relative Error (%) = Mean Error x 100

True Value
Relative Error is generally Expressed as a Percentage (%).

Dr Prakash Katakam
Types of Errors
Two types of errors are present. They are

1. Determinate error (= constant error)
2. Indeterminate error (= Random or accidental error)
Determinate Errors:
• They can be determined.
• They can be avoided.
• They can be corrected.
They are usually present in each measurement an affect all observations of a

series in the same way.
Eg: Error in weighing operation, error in weighing operation, error in volume
measurement.
Indeterminate Errors:
• They can not be determined.
• They can not be avoided.
• They can not be corrected.
They vary from one measurement to the next. They result from pure random
fluctuations.
Eg: Weight of capsules after filling.
Errors must be eliminated as far as possible.

Dr Prakash Katakam
SOLUTION AND SOLUBILITY

DEFINITIONS:
True Solution: is defined as a mixture of two or more components that form a

homogeneous molecular dispersion or, a one-phase system in different compositions.
A solution composed of only two substances is known as Binary solution, and

components are known to as the solvent and solute.
System: is a bounded space or definite quantity of substance. Eg. Magnetic Field,

Solution, Emulsion, Suspension.
Phase: is defined as a distinct homogeneous part of a system separated by definite

boundaries from other parts of the system. Eg. Ice in water, oil-water, emulsion and
suspension.
Phase: is two types : Homogeneous and Heterogeneous Phase
Homogeneous: One Phase, Eg. Sugar solution
Heterogeneous: More than one Phase, Eg. Emulsion and suspension
Coarse Dispersions: Particle Size 0.1mm (100Å or 10-5 cm) :

Liquid-Liquid (Oil-Water: Emulsions), Solid-Liquid (Suspensions), Liquid-Air
(Aerosol spray), Solid-Air (Spray powders).
Colloidal Dispersions: Particle size very small, 10 to 5000 Å.

May be homogeneous (acacia in water or gels), or Heterogeneous (gold solution)
Saturated Solution: is where solute (in solution) is in equilibrium with solute (in
solid phase).
Solubility:
Quantitative terms: Defined as the concentration of solute in a saturated
solution at a given temperature.
Qualitative terms: Defined as the spontaneous interaction of two or more
substances to form a homogeneous molecular dispersion.
Unsaturated solution: Solute concentration is below saturation at a given

temperature.
Supersaturated solution: Solute concentration is above saturation concentration at a

given temperature and contains precipitates. Super saturation occurs by reducing
Temperature or presence of nuclei solids. Eg. Crystallization of Sugar or Salt.
Solubility Expressions:

Dr Prakash Katakam
U.S.Pharmacopoeia and National Formulary (USP-NF): defines solubility as the

number of ml of solvent in which 1gm of solute will dissolve. Eg. 1gm of Boric Acid
dissolves in 18 ml of water, in 18 ml of alcohol and in 4ml of glycerin.
Solubility Expressions or Concentration Expressions:

Expression Symbol Definition
Molarity M,c Moles (gram molecular weights) of solute in 1 litre (1000ml) of
solution.
Molality m Moles of solute in 1000 gm of solvent
Normality N Gram equivalent weights of solute in 1 litre of solution
Mole x Ratio of moles of solute to total moles of solute+solvent
Fraction
Percentage %w/w gm of solute in 100gm of solution
by Weight
Percentage %v/v ml of solute in 100ml of solution
by Volume
Percentage %w/v gm of solute in 100 ml of solution
For substances not having definite solubility the Terms of Approximate

Solubility are used:
Term Parts of Solvent Required for 1 part of
Solute
Very Soluble Less than 1 part
Freely Soluble 1 to 30 parts
Soluble 10 to 30 parts
Sparingly Soluble 30 to 100 parts
Slightly Soluble 100 to 1000 parts
Very Slightly Soluble 1000 to 10,000 parts
Practically Insoluble More than 10,000 parts
Principles of Solubility: Solubility of solute in solvent depends on following

Principles:
¾ If Structural Similarity between solute and solvent are greater, then the
solubility is more. Eg. Alcohol in Water and Glucose in water.
¾ Polar solutes dissolve in Polar solvents easily (Eg. NaCl in Water)
¾ Non-polar solutes dissolve in Non-polar solvents (Eg. Naphthalein in
Benzene).
¾ Semi-polar solvents like alcohol have intermediate properties (Eg. Boric acid
is slightly soluble in alcohol).
¾ Solubility of polar solute decreases by adding Non-Polar solvents. (Eg.
Solubility of Glucose in Water by adding Benzene)

Dr Prakash Katakam
SOLUBILITY OF LIQUIDS IN LIQUIDS (MISCIBILITY):

Miscibility: refers to the mutual solubilities of the components in liquid-liquid
systems.
Complete Miscibility: Mix in all proportions (any %).

Eg. Polar and semipolar solvents, like water-alcohol, glycerin-alcohol, alcohol-
acetone.
Nonpolar solvents like Benzene-carbon tetrachloride are completely miscible.
Partial Miscibility: Two slightly miscible liquids. Eg. Water and Phenol are mixed;
two liquid layers are formed containing one liquid in small quantity dissolved in
another liquid.
The mutual solubility of partially miscible liquids are influenced by Temperature and
other substances.
Influence of Foreign Substances: Addition of a substance to a Binary (2-phase)

Liquid System produces a Ternary (3-phase) System, that is, having 3 components.
If this 3rd substance is soluble with any one of the constituents of binary system, then
the mutual solubility of the components of binary system will change.
Eg: If 0.1M naphthalene is added to Phenol-Water, it dissolves only in Phenol and
raises the solubility temperature about 20oC.
If 0.1 M KCl is added to Phenol-Water, it dissolves only in Water and raises the
solubility temperature about 8oC. This is known as Salting-out effect.
If 3rd substance is soluble in both liquids, the mutual solubility of liquids increases,
Eg. Succinic acid is added to Phenol-Water system.
Effect of Dielectric Constant: As dielectric constant increases, the solubility also

increases. Eg. Polar solvents like water and alcohol have high dielectric constants.
Non polar solvents like Benzene, Chloroform have low dielectric constants.
Therefore the solutes with low dielectric constants dissolve easily in low dielectric
constant solvents and vice-versa (reverse case). Eg. Chloroform and Benzene &
Water and Alcohol miscible easily.
Dielectric constant value is ≥ 1. Eg. Vacuum is 1.0, Water is 80, Paper is 3.6.

Dr Prakash Katakam
Polarity of some solvents and the solutes that readily dissolve in each class of
solvent.
Dielectric Solvent Solute

constant
Å--------Decreasing Water Solubility-----

Å------------Decreasing Polarity----------
of solvent
ε
(approx.)
80 Water Inorganic salts, organic salts
50 Glycols Sugars, tannins
30 Methyl and Ethyl Alcohols Caster oil, waxes
20 Aldehydes, ketones and Resins, volatile oils, weak
higher alcohols, ethers, esters electrolytes including barbiturates,
and oxides alkaloids and phenols
5 Hexane, benzene, carbon Fixed oils, fats, petrolatum,
tetrachloride, ethyl ether, paraffin, other hydrocarbons
petroleum ether
0 Mineral oil and fixed
vegetables
Solubility of Non-ionic Solids in liquids:
Ideal Solutions:
In Ideal solutions there is no change in the properties of the components, except
dilution. No heat is evolved or absorbed during the mixing process, and the final
volume of the solution represents an additive property of individual constituents.
Eg. 100ml Methyl alcohol and 50 ml Ethyl alcohol gives 150 ml total volume, no heat
is evolved or absorbed.
The solubility of solid in an ideal solution depends on temperature, melting point of

the solid, and molar heat of fusion ΔHf, (that is, the heat absorbed when the solid
melts).
In an Ideal solution the Heat of Solution = Heat of Fusion, independent of
temperature.
Ideal solubility is not influenced by nature of solvent.
Thermodynamics Formula for an Ideal solution of a solid in a liquid is:
ΔH f ⎛ T0 − T ⎞
− log X 2i = ⎜ ⎟
2.303R ⎜⎝ TT0 ⎟⎠
ΔHf = molar heat of fusion

X 2i = ideal solubility of the solute (mole fraction)
T0 = melting point of solid solute in absolute degrees
T = absolute temperature (273 oK)
R = gas constant
At temperature above melting point, the solute is in the liquid state

Dr Prakash Katakam
In an ideal solution, the liquid solute is miscible in all proportions with solvent.
Above equation is not valid when T > T0.
The molar heat of fusion is determined by differential scanning calorimetry.
Drugs ΔHf (cal/mole)

Benzoic acid 4302
Caffeine 5044
Iodine 3740
Stearic acid 13524
Sulphur 4020
Testosterone 6760
Non-Ideal Solutions:
In Non-deal solutions or Real solutions, heat is absorbed or evolved.
Eg. H2SO4 in water evolves heat.
The activity of a solute in a solution = concentration X activity coefficient
or a 2 = X 2γ 2
a2 = activity
γ 2 = activity coefficient
X2= concentration
In Ideal solution, a2 = X 2i , since γ 2 =1
The mole fraction solubility of a solute in a Nonideal solution, expressed in log form,
ΔH f ⎛ T0 − T ⎞
− log X 2 = ⎜ ⎟ + log γ 2
2.303R ⎜⎝ TT0 ⎟⎠
Therefore, the mole fraction solubility in various solvents can be expressed as the sum
of two terms: the solubility in an ideal solution and the logarithm of the activity
coefficient of the solute.
log γ 2 is obtained by intermolecular forces of attraction or the work done in removing
a molecule from the solute phase and depositing it in the solvent.

Dr Prakash Katakam
Three steps are involved in the solubility mechanism.
Total work involved in the above interaction = w22 + w11 – 2w12.

w22 = gain in energy for releasing of solute molecule
w11 = interaction energy between solvent molecules, creation of hole
2 w12 = interaction energy of solute with solvent
Solubility Parameters: (Hildebrand)

Solubility parameters express the cohesion between like molecules, may be calculated
from heats of vaporization, internal pressures, surface tensions, and other properties.
It is square root of internal pressure
1/ 2
⎛ ΔH v − RT ⎞
δ = ⎜⎜ ⎟⎟
⎝ Vl ⎠
ΔH v = the heat of vaporization

Vl = molar volume of the liquid at desired temperature
R = gas constant
T = absolute temperature
Internal pressure (cal/cm3)is the attractive forces, occur in gases, liquids or solids.

Dr Prakash Katakam
Extended Hildebrand Solubility (EHS) Approach:

EHS allows to calculate the solubility of polar and nonpolar solutes in solvents
ranging from nonpolar hydrocarbons to highly polar solvents such as alcohols,
glycols, and water.
EHS is used for crystalline solids-liquid, liquid-liquid and gas-liquid systems.
The solubility equation used in EHS approach is
− log X 2 = − log X 2i + A( w11 + w22 − w12 )

Where,
V2φ12
A=
2.303RT
V2 = volume per mole of liquid solute
φ 1= volume fraction of solvent
R = gas constant
Solubility of salts in water (Strong Electrolytes)

When a salt is dissolved in water, the process may be,
Endothermic process: absorption of heat (solution becomes cool). Solubility increases
when heated.
Exothermic process: heat is released (solution becomes hot). Solubility decreases
when heated.
If no heat is released or absorbed, then effect of temperature on solubility is not
present.
Eg. NaCl. in water.
Heat of Solution ΔH: It is the heat absorbed per mole when a small quantity of solute
is added to a large quantity of solution.
Heat of sublimation is the heat liberated when solid state goes into gaseous state.
(Camphor)
Heat of Hydration (solvation) is the heat liberated when gaseous ions are hydrated.
ΔH (solution) = ΔH sublimation + ΔH hydration
Gibb’s Phase Rule

F=C–P+1
F = degrees of freedom
C = number of components
P = number of phases

Dr Prakash Katakam
Eg. If NaCl is dissolved in water, becomes solution and it has, C = 2, P = 1

and
Hence F = 2 – 1 + 1 = 2
If NaCl is saturated, crystals are found in the solution and, C = 2, P = 2 and
Hence F = 2 – 2 + 1 = 1
Solubility of slightly water soluble electrolytes:

When slightly soluble electrolytes are dissolved to form saturated solutions, the
solubility is described by a special constant, called as “Solubility Product”, Ksp, of the
compound.
Substance Solubility Product, Ksp Temperature oC

Calcium carbonate 9 x 10-9 25
Magnesium carbonate 2.6 x 10-5 12
Silver chloride 1.25 x 10-10 25
Zinc sulfide 1.2 x10-23 18
Excess solid in equilibrium with the ions in saturated solution at a specific

temperature is represented by the equation
AgClsolid Ag+ + Cl-
Because, the salt dissolves only with difficulty and the ionic strength is low, the
equilibrium expression may be written in terms of concentrations instead of activities:
[Ag+] [Cl-] = K
[AgClsolid]
Since the concentration of the solid phase is constant therefore AgClsolid is ignored.
[Ag+] [Cl-] = Ksp
Similarly for, aluminium hydroxide, Al (OH)3, [Al3+] [OH-]3 = Ksp
This equation is applicable for Slightly Soluble Solids. It is not suitable for freely
soluble salts like NaCl.
If a common ion (like Ag+ or Cl-), is added to a solution of AgCl solution, the
equilibrium is altered, and solubility of AgCl is reduced. Hence the result of adding a
common ion is to reduce the solubility.
If a salt other than common ion is added then they increase the solubility because they
lower the activity coefficient.
If the pharmacist wishes to prevent precipitation of a slightly soluble salt in water, a

compound may be added that will tie up with one of the ions. Then more of the salt
will pass from solid state to dissolved state.
Eg. Fe(OH)3 salt is slightly soluble in water. The solubility can be increased by
adding Sodium Citrate that dissolves more Fe3+ ions.

Dr Prakash Katakam
Solubility of Weak Electrolytes:

Many important drugs are weak acids and weak bases. They react with strong acids
and bases, soluble in water and exist as ions at definite pH.
Weak acids are freely soluble in dilute bases, but precipitate in presence of strong
acids by replacing weak acids. Eg. Benzoic acid is freely soluble in dilute NaOH, but
get precipitated when HCl is added to it.
Benzoic acid + NaOH ---Æ Sodium Benzoate + water, then +HCl------ÆBenzoic acid
+ NaCl
Similarly weak bases are freely soluble in dilute acids, but precipitate in presence of
strong bases by replacing weak bases. Eg. Caffeine is freely soluble in dilute Citric
acid forming Caffeine citrate, but when NaOH solution is added to it, Caffeine gets
separated.
Caffeine + Citric acid ------Æ Caffeine citrate, then + NaOH------Æ Caffeine + Na
Citrate
Calculating the Solubility of Weak Electrolytes influenced by pH:
The solubility of weak electrolytes is strongly influenced by the pH of the solution.

Weak Acids: in soluble ionic form converted into molecular form as pH is lowered
and further precipitated.
Weak Bases: in soluble ionic form converted into molecular form as pH is increased
and further precipitated.
Therefore a specific pH is required for good solubility of weak electrolytes.
Optimum pH required is calculated as follows:

(a) For weak Acids: Eg. Phenobarbital, (b) For weak Bases: Eg. Ammonium
Hydroxide
S − S0
pH p = pK a + log
S0
or
S0
pH p = pK w − pK b + log
S − S0
pHp = pH below which the drug separates from solution as undissociated acid or
pH above which the drug separates from solution as undissociated base
pKa = Dissociation constant of acidic drug
pKb = Dissociation constant of basic drug
S = Concentration of drug initially added as the salt
S0 = molar solubility of free undissociated acid or base

Dr Prakash Katakam
Influence of Solvents on Solubility of Drug:

All drugs are not soluble in water alone. Poorly soluble drugs may be dissolved in
presence of other solvent.
Cosolvency: increasing solubility of a drug in a solvent by adding another solvent or
mixture of solvents is called Cosolvency and the solvents used to increase solubility
are called as “Cosolvents”.
Selection of cosolvent is based on the polarity required by the solute.

Benzoic acid is slightly soluble in water, but when alcohol is added to water, it is
soluble freely.
Eg. 1 gm of Phenobarbital is soluble in 1000 ml of water, in 10 ml of alcohol, in 40

ml of chloroform and in 15 ml of ether at 25 0C.
Based on this information, the quantities of cosolvents required are determined

experimentally.
Eg. To convert a suspension formulation into a solution formulation alcohols are
popularly added. Piperazine Citrate Elixir contains about 15% of alcohol.
Combined Effect of pH and Solvents:

When solvent is added to a solution of electrolyte, the pH and pKa also will change.
Eg. The pKa of Phenobarbital, 7.41, is raised to 7.92 when alcohol is added to 30%,
and solubility of unionized Phenobarbital increases from 0.12% to 0.64%. Therefore
pH also reduced.
Influence of Complexation and Particle Size:

Complexation: Many liquid preparations (syrups) contain more than one drug in
solution. More than one drug and other additives in the solvent may interact each
other resulting in insoluble complexes. Therefore necessary action should be taken to
prevent this interaction, or to minimize the effect of formed complexes, like
converting into a stable suspension form.
Size of the particles also affects solubility. Solubility increases with decreasing
particle size because of increased surface area and increased contact of solvent with
solute.
Stable crystals are less soluble compared to non-stable amorphous forms.

Eg. Sugar crystals are less soluble compared to broken sugar amorphous form. This is
because solubility depends on work required to separate the particles of the crystalline
solute is more for crystals with compact packing.

Dr Prakash Katakam
COLLIGATIVE PROPERTIES OF SOLUTIONS
Properties of Solutions:
(a) Colligative properties: depend mainly on the number of particles in a
solution. The properties are osmotic pressure, vapor pressure lowering,
freezing point depression and boiling point elevation.
(b) Additive properties: depend on total contribution of atoms in the
molecules (or) on the sum of the properties of the constituents in a
solution. Eg. Molecular weight and sum of total mass of components.
(c) Constitutive properties: depend on arrangement of atoms within a
molecule.
Refraction of light, electric properties, surface and interfacial characteristics,

and the solubility of drugs are partly additive and partly constitutive
properties.
The solutes are divided into two main classes: Nonelectrolytes and
Electrolytes.
Nonelectrolytes are substances that do not yield ions when dissolved in water
and do not conduct electric current through the solution. Eg. Sucrose,
glycerin, naphthalene and urea.
Electrolytes are substances that form ions in solution, conduct electric current,
and show some colligative properties. Strong and Weak electrolytes are
possible depending on whether the substance is completely or partly
ionized in water. HCl and Sodium sulphate are strong electrolytes &
ephedrine and Phenobarbital are weak electrolytes.
Osmotic Pressure:
Diffusion: Free movement of both solute and solvent molecules across a

membrane. Eg. Cobalt chloride is
placed in a parchment sac (membrane
bag) and suspended in water, the water
gets gradually red color.
Osmosis: If the membrane
(Semipermeable membrane) is
permeable to only solvent molecules,
the phenomenon known as Osmosis
(greek: Push or Impulse). Movement of
solvent molecules from lower
concentration to higher concentration
across a semipermeable membrane.

Dr Prakash Katakam
The wide opening part of a thestle tube (like Funnel shape) is tied with
cellophane membrane and filled with concentrated sugar solution and
immersed in water as shown in Figure.
Water slowly enters the tube through the membrane (because of Escaping
Tendency) and raises the level of sugar solution until the hydrostatic
pressure of column of liquid equals the pressure causing the water to pass
through the membrane and enters thistle tube and stops.
Eg. Dry fruits in water, Grapes, etc.
Events in Osmosis:
(1) The addition of non-volatile solute to the solvent forms a solution in
which the vapor pressure of the solvent is reduced (see Raoult’s Law).
(2) If pure solvent and this solution is separated by Semipermeable
membrane, solvent molecules will pass through membrane to dilute the
solute and raise vapor pressure back to its initial value.
(3) This osmotic pressure can be determined by measuring Hydrostatic head
appearing in solution or by applying a known pressure that just stops the
osmotic pressure and prevents solvent molecules movement.
The osmotic pressure obtained is proportional to reduction in vapor pressure

resulted from concentration of solute present.
This is a function of molecular weight of solute, osmotic pressure is a
colligative property used to determine the Molecular Weights.
Osmotic pressure Osmometer: works on the principle of Thestle tube above.
After equilibrium, the height difference in capillary tube is h (also called as
hydrostatic head ) on water side.
Osmotic pressure π (atm) = height h × solution density ρ× gravity acceleration

g.

Dr Prakash Katakam
Molecular Weight Determination: for nonelectrolyte solutions.

The lowering of vapor pressure of solution containing a nonvolatile solute
depends only on the mole fraction (Concentration) of solute.
Number of Moles of solvent, n1 = w1 / M 1
Number of Moles of solute, n2 = w2 / M 2 , where w1 and w2 are weights of
solvent and solute of molecular weights M1 and M2 respectively.
Therefore Eqn. (from Lowering of Vapor Pressure) may be recalled here.
p1o − p Δp n2
= o = X2 = ,
o
p1 p1 n1 + n 2
where Δp = p1o − p is the lowering of the vapor pressure and
Δp / p1o is the relative vapor pressure lowering.( which depends on mole fraction
of the solute X2, that is number of solute particles in a definite volume of
solution.)
The above equation can be assessed as,

p1o − p n2 w2 / M 2
= =
o
p1 n1 + n2 w1 / M 1 + w2 / M 2
For dilute solutions w2 / M 2 (mole fraction of solute) is negligible compared
with (mole fraction of solvent) w1 / M 1 , therefore w2 / M 2 may be removed from
denominator, and equation gives as,
Δp w2 / M 2
=
p1o w1 / M 1
Therefore the molecular weight of Solute M2 is obtained by rearranging above

equation.
w2 M 1 p10
M2 =
w1 Δp
Choice of Colligative Properties: in the determination of molecular weight of

solute
• Boiling Point Method can be used only when the solute is nonvolatile
and when the substance is not decomposed at boiling temperatures.
• Freezing Point (Cryoscopic Method) Method is used for solutions
containing volatile solutes (alcohol), since the freezing point of a solution
depends on the vapor pressure of the solvent alone. It is also used for solutions
of small molecules.
• Both above two methods are difficult to conduct at constant
temperatures.
• Osmotic Pressure Method is used for polymers of high molecular
weight.

Dr Prakash Katakam
BUFFERED AND ISOTONIC SOLUTIONS
Definition
Buffers are compounds in solution resist changes in pH upon the addition of small
quantities of acid or alkali.
The resistance to a change in pH is known as Buffer Action.
A combination of a weak acid and its conjugate base (i.e. its salt), or
A weak base and its conjugate acid (ie. Its salt) act as buffers.
If strong acid, HCl is added to a 0.01 M solution of Acetic acid (weak acid) + sodium
acetate (conjugate base), the change in pH is only 0.09 pH units, because Ac- ties up
the H+ ions according to the reaction.
Ac- + H3O+ HAc + H2O
If a strong base, NaOH, is added to the buffer mixture, acetic acid neutralizes the OH-
ions as follows:
HAc + OH- H2O + Ac-
Buffer Equation for weak acids

The H of a buffer solution and the change in pH upon the addition of an acid or base
may be calculated by use of the Buffer Equation.
When sodium acetate is added to acetic acid, the dissociation constant for the weak
acid,
[ H O + ][ Ac − ]
Ka = 3 = 1.75 × 10 −5
[ HAc]
Ka is temporarily disturbed since the Acetate ion supplied by the salt increases the
[Ac-] term in the numerator. To reestablish the constant Ka at 1.75 x 10-5, the
hydrogen ion term in the [H3O+] is suddenly decreased, with an increase in [HAc].
Therefore the constant Ka is not changed and equilibrium is shifted in the direction of
the reactants. The ionization of acetic acid, HAc + H2O H3O+ + Ac-, is
inhibited by the addition of common ion [Ac-]. This is an example of the Common Ion
Effect.
The pH of the final solution is obtained for acetic acid:

[ HAc]
[ H 3O + ] = K a
[ Ac − ]
or
[acid ]
[ H 3O + ] = K a
[ salt ]

Dr Prakash Katakam
If the acid is weak ad ionizes only slightly, HAc may be considered as total
concentration of acid [acid] and 1mole of acetate ion [Ac-] is equal to total salt
concentration [salt].
Therefore the Buffer Equation or the Henderson-Hasselbalch equation, for weak acid
and its salt:
[ salt ]
pH = pK a + log
[acid ]
pKa, the negative logarithm of Ka, is called the Dissociation exponent.
Buffer Equation for weak bases

The buffer equation for solutions of weak bases and the corresponding salts may be
similar to the above equation,
[base]
pH = pK w − pK b + log
[ salt ]
Drugs as Buffers
Drugs are weak electrolytes, i.e., weak acids, weak bases, salts of weak acids or bases.
Hence they behave like buffers in solutions.
Eg: Salicylic acid in soft glass bottle is effected by alkalinity of glass. It is expected
that alkali of glass will react with salicylic acid and increase the pH. But the salt
(sodium salicylate) formed will combine with salicylic acid gives a buffer that resist
the changes in pH.
Similarly Ephedrine + HCl gives Ephedrine hydrochloride, which forms buffer with
pure Ephedrine and resist changes in pH, thus acting like buffer.
Generally the drug solutions behave like buffers to some extent only. Additionally
external buffers are to be added to maintain constant pH.
Buffer Capacity:
The magnitude (extent or level) of the resistance of a buffer to pH changes is known
as Buffer Capacity β. It is expressed in quantitative terms.
It is also known as buffer efficiency, buffer index, and buffer value.
It is the ratio of increment of strong base (or acid) to the small change in pH brought
about by this addition.
ΔB
β=
ΔpH
In which delta (Δ), has meaning “a finite change”, and ΔB is the small increment in
gram equivalents per liter of strong base added to the buffer solution to produce a pH
change of ΔpH.
According to above equation the buffer capacity of a solution has a value of 1 when
the addition of 1 gram Equivalent of strong base (or acid) to 1 liter of the buffer
solution results in a change of 1 pH unit.

Dr Prakash Katakam
Pharmaceutical Buffers
Buffer solutions are used frequently in formulation of ophthalmic solutions.
Boric acid and sodium carbonate in various concentrations give buffer solutions of pH
6 to 8.
HCl and KCl, pH 1.2 to 2.2
HCl and Potassium hydrogen phthalate, pH 2.2 to 4.0
NaOH and potassium hydrogen phthalate, pH 4.2 to 5.8
NaOH and KH2PO4, pH 5.8 to 8.0
H3BO3, NaOH and KCl, pH 8.0 to 10.0
Tissue Irritation
Solutions used for parenteral administration and tissues will cause irritation if the pH
is not equal to body fluid.
Tissue irritation is minimum when,
(a) the lower buffer capacity of solution,
(b) small volume of solutions,
(c) larger buffer capacity of body fluids.
Buffer capacity of Boric acid is low compared to phosphate buffer. Hence boric acid
is used for ophthalmic solutions.
Parenteral solutions for injection into the blood are weakly buffered, hence the
solution changes its pH soon after it reaches the blood circulation.
For nasal preparations also buffering is important.
Buffered Isotonic Solutions

The parenteral preparations and eye preparations should be adjusted with pH and also
they should have same Osmotic Pressure as that of body fluids.
0.9% w/v of NaCl in water is isotonic with body fluids.
2% w/v of Boric acid in water is also Isotonic with body fluids.
Isotonic means the solutions will have same salt concentration as that of body fluids.
Hypertonic Solution: If the solution is having more osmotic pressure than body
fluids. If red blood cells are suspended in a 2% NaCl solution, the water from the
RBC will move outwards and the cells will shrink.
Hypotonic Solution: If the solution is having less osmotic pressure than body fluids.
If red blood cells are suspended in a 0.2% NaCl solution, the water will enter the RBC
and the cells will burst, causing Hemolysis.
Therefore the parenteral and ophthalmic solutions should be buffered and made
isotonic.
Measurement of Tonicity
1. Hemolytic Method: liberation of Oxyhemoglobin in hypotonic solution is directly
proportional to number of cells hemolyzed.
2. Based on change in temperature when salt is added to solutions. The freezing point
of blood and and tears is -0.52oC, corresponding to the freezing point of 0.9% NaCl
solution.

Dr Prakash Katakam
ΔT f
Liso =
c
because, c =
w 1000
c= ×
MW v
therefore
w × 1000
ΔT f = Liso ×
MW × v
Liso = molar freezing point depression of the drug at a concentration nearly isotonic
with blood and lacrimal fluids.
ΔTf = Freezing point depression of a some % solution of the drug.
c = molarity (=moles/liter)
w = weight in gm of solute
MW = molecular weight of solute
v = volume of solution in ml.
The Liso value for a 0.9% (0.154 M) NaCl solution, which has freezing point
depression of 0.52oC and isotonic with body fluids.
= 0.52 = 3.4
0.154
Problem: What is the freezing point lowering of a 1% solution of sodium propionate
(Mol. Wt. 96)? Liso value is 3.4. The molar concentration of 1% solution is 0.104.
1 × 1000
ΔT f = 3.4 × = 3.4 × 0.104 = 0.35 0
96 × 100

Dr Prakash Katakam
Methods of Adjusting Tonicity and pH
Class 1 Methods:
(a) Cryoscopic Method
(b) Sodium Chloride Equivalent Method
Class 2 Methods:
(c) White Vincent Method
(d) Sprowls Method
In Class 1 Methods, NaCl or some other substance is added to the solution of the drug
to lower the Freezing Point of the solution to -0.52 oC. Therefore the solution
becomes Isotonic.
In Class 2 Methods, sufficient quantity of Water is added to drug to form an isotonic

solution. Final volume is adjusted with a buffered isotonic solutioin.
(a) Cryoscopic Method: The freezing point depressions of some drugs are given in
the following table.
Substance MW Ε V ΔTf1% Liso

Alcohol 46.07 0.70 23.3 0.41 1.9
Boric acid 61.84 0.50 16.7 0.29 1.8
Caffeine 194.19 0.08 2.7 0.05 0.9
Dextrose 198.17 0.16 5.3 0.09 1.9
Glycerin 92.09 0.34 11.3 0.20 1.8
Phenol 94.11 0.35 11.7 0.20 1.9
Sodium chloride 58.45 1.00 33.3 0.58 3.4
Sucrose 342.30 0.08 2.7 0.05 1.6
Tetracycline 480.92 0.14 4.7 0.08 4.0
HCl
Apomorphine 312.79 0.14 4.7 0.08 2.6
HCl
Procaine HCl 272.77 0.21 7.0 0.12 3.4
MW = molecular weight of solute

E = NaCl equivalent of the drug. (quantity of NaCl that is equivalent to 1 gm of
drug that has same osmotic pressure).
V = volume (ml) of Isotonic solution that can be prepared by adding water to
0.3gm of drug.
ΔTf 1% = Freezing point depression of 1 % solution of the drug.
Liso = molar freezing point depression of the drug at a concentration nearly
isotonic with blood and lacrimal fluids.
Example: How much NaCl is required to give 100 ml of 1% solution of Apomorphine

HCl) isotonic with blood serum?

Dr Prakash Katakam
Solution: From the above table it is found that a 1% drug solution has freezing point
lowering of 0.08o.
The freezing point lowering of blood is 0.52o.
The freezing point lowering of 1% NaCl is 0.58o.
Therefore the difference in the freezing point lowering to reduce the freezing point is
= 0.52 – 0.08 = 0.44o.
By the method of proportion,

1% 0.58 o
=
X 0.44 o
X = 0.76%
Thus 0.76% NaCl will lower the freezing point of the required 0.44o and make the
solution isotonic.
The isotonic solution is prepared by dissolving 1 gm of Apomorphine HCl and 0.76
gm of NaCl in 100 ml water.
(b) Sodium Chloride Equivalent Method:

The NaCl equivalent is the quantity of NaCl that is equivalent to 1 gm of drug that is
having the same osmotic pressure.
The NaCl equivalent E for drugs are given in above table.
Liso
Formula to calculate E for drug = E = 17
MW
Example: Calculate the E value for Apomorphine HCl (Liso value is 4 and MW is
480.92).
4
E = 17 = 0.14
480.92
Example : Prepare 100ml of isotonic solution of Apomorphine HCl with a dose of
0.2 gm.
Step 1: Multiply the quantity of drug by its sodium chloride equivalent, E, to give the
weight of NaCl to which the drug is osmotically equivalent.
= 0.2 gm X 0.14 = 0.028 gm of NaCl.
Step 2: Substract the above value from concentration of NaCl isotonic solution
(0.9% or 0.9 gm in 100 ml).
= 0.9 gm of NaCl – 0.028 gm of NaCl = 0.872 gm of NaCl

Dr Prakash Katakam
Therefore 0.872 gm of NaCl is required to make isotonic solution along with 0.2 gm
of Drug.
(C) White-Vincent Method: Involves addition of water to drugs to make an isotonic

solution. Then add isotonic buffered diluting solution to bring the solution to final
volume.
Example: Make 30 ml of 1% solution of Procaine HCl isotonic with body fluids.
Step 1: The weight of the drug (w) is multiplied by NaCl equivalent (E). and then
multiplied by constant 111.1 (=100/0.9)
= 0.3 gm X 0.21 = 0.063 gm.
= 0.063 gm of NaCl osmotically equivalent to 0.3 gm of Procaine HCl.
Step 2: We know that 0.9 gm of NaCl in 100 ml gives isotonic solution. The volume
V of isotonic solution that can be prepared from 0.063 gm of NaCl (equivalent to 0.3
gm of Procaine HCl) is obtained by,
0.9 gm 0.063 gm
=
100ml V
100
V = 0.063 × = 7.0ml
0 .9
Final Formula: V = w . E . 111.1

Step 3: Then 30ml – 7ml = 23 ml of another isotonic solution is added to 7 ml to
make 30 ml of total volume of isotonic Drug solution.
So, Procaine HCl is dissolved in 7 ml of water to make isotonic solution. Then it is

made up to 30 ml by adding isotonic diluting solution.
(d) Sprowls Method: The equation, V = w . E . 111.1, can be used to calculate the
V values for many drugs. The standard values can be used for calculations directly.

Dr Prakash Katakam
COLLOIDS
Introduction
The term colloid means GLUE-LIKE substances.
Colloidal system is a dispersion where dispersed particles are distributed uniformly in
a dispersion medium.
Colloidal systems are defined as those polyphasic systems where at least one
dimension of dispersed phase measures between 10-1000 A (angstroms) to few
microns.
Types of Colloidal System

Colloidal systems are classified into two types, positive and negative colloids
depending on the charge on the dispersed particles.
Based on the interaction of dispersed particles with molecules of dispersion medium,
colloidal dispersions are classified into 3 categories.
a) Lyophilic colloids
b) Lyophobic colloids
c) Association colloids
Lyophilic colloids: Lyophilic means “Solvent Loving”. The dispersed particles have
greater liking towards the dispersion medium (solvent).
The dispersion medium forms a sheath around the colloidal particles and solvates.
This makes the dispersion thermodynamically more stable. The particles can be
precipitated easily and re-dispersed easily too.
Dispersed particles may be Hydrophilic- means water loving. Eg. Acacia, gelatin,
albumin, insulin.
Dispersed particles may be Hydrophobic – means oil loving. Eg. Rubber, polystyrene,
benzene, etc.
Therefore based on the nature of the particles, dispersion medium like water or
organic solvent may be selected for Lyophilic colloids.
Lyophobic colloids: (Lyo – means solvent, phobic means hating). These dispersions
have very little attraction between dispersed phase (solids) and dispersion medium
(liquid).
These are stable because of the presence of a charge (+ve or –ve) on the particles.
Like charges (+ &+ or –& –) on the particles keep them away from each other and
uniform dispersion is possible because of Repulsion Forces.

Dr Prakash Katakam
Solvent sheath around the particle is not present. Therefore they are
thermodynamically unstable.
Hydrophobic dispersions: gold, silver, sulfur, etc.
Association colloids: The “Amphiphiles” are molecules or ions which have some
liking for both Polar and Nonpolar solvents. They have both polar and non polar
groups.
Eg. Surfactants like Tween 80 and sodium lauryl sulphate.
Critical Micellar Concentration (cmc): is defined as the concentration range of a

surfactant at which Micelles start forming. Micelle means a smallest spherical
surfactant pocket.
Cmc: is a concentration like w/w, moles/1000 gm.
Below cmc the surfactant molecules are adsorbed at Air-Water interface. As the
concentration of surfactant increases, the molecules get accumulated and enter into
the water medium and form Monolayer Micelle (Single layer spherical shape).
If we add the surfactant further, the Monolayer micelles get saturated and formation
of Laminar multilayer micelles.

Dr Prakash Katakam
Pharmaceutical applications of colloids:

1. Therapy: colloids show better therapeutic action: colloidal particles of metals
Silver – germicidal
Copper – anticancer
Mercury - anticancer
Route of administration: oral and parenteral injections.
2. Absorption and toxicity: Colloidal sulfur shows better and faster absorption
compared to coarse dispersion of sulfur. Also toxicity will be more for colloidal
dispersions.
3. Solubility: Solubility of drugs is improved by using colloidal systems containing

surface active agents. Eg. Solubilization of sulfonamides and Phenobarbital are made
soluble.
4. Stability: Dispersions of surface active agents are called as Association Colloids.

These are used to improve stability of drugs in liquid dosage forms.
Colloidal dispersion of big-molecules like Gelatin (protein) and synthetic polymers
(Methyl cellulose) are used as coating solutions for tablets.
Colloidal systems are used as pharmaceutical additives, vehicles, carriers and product
components.
5. Targeting of drugs to specific organs: In novel drug delivery systems, colloids are
used in Targeting the drugs to specific body organs like liver and spleen.
Eg.
a) Liposomes:- nano-level emulsions made from Cholesterol
b) Niosomes:- made from surfactants
c) Nanoparticles:- small particle suspensions of size in nanometers
d) Micro-emulsions:- globule size is in microns in the emulsions.
Colloidal systems that are official and meant for parenteral use:
Eg.
a) Iron dextran injection B.P.: contains dextran (polymer of dextrose) with
ferric ions. Used in treatment of anemia. It is an example for nonionic
hydrophilic sol.
b) Iron sorbitol injection B.P.: contains sorbitol, dextran and citric acid
complexes with ferric ions.

Dr Prakash Katakam
Stability of colloidal systems

Good stability means no particle aggregation.
Stability is achieved by maintaining the particles in Brownian motion. Two ways:-
(a) Providing electric charge (like charge) on the surface of the dispersed particle
(in Lyophobic colloids).
(b) Maintaining solvent sheath (sheet) around the particle (in Lyophilic colloids).
Lyophobic Colloids:
Stability is explained by DLVO (Deryagin, Landau, Verwey and Overbeek)
theory. According to this, the distance between two dispersed particles mainly
influences particle-particle interactions. They are attraction and repulsion interactions.
Attraction results in aggregation of particles and repulsion results in maintaining
dispersion of the particles. Using this theory one can determine the amount of
electrolyte required to precipitate or stabilize the colloid. The following figure shows
that there are three types of forces of interaction.
(a) Van der Waals attraction forces: depend on size and chemical nature of
particles. The potential energy of attraction is represented by VA.
(b) Electrostatic repulsive forces: depend on density, surface charge and thickness
of double layer. The potential energy of repulsion is denoted by VR.
(c) Net energy of interaction: it is the Algebraic addition of above two forces and
represented by VT.

Dr Prakash Katakam
Primary Minimum (sign of Precipitation): when particles are very close to each other,
atomic orbitals overlap and penetrate each other. Therefore there is rapid rise in
potential energy.
Primary Maximum (Net energy Peak) (sign of better stability): at intermediate
distances, repulsive forces operate (positive Zeta potential). This keeps the particles in
Brownian movement and gives stability to colloidal dispersion.
Secondary Minimum (sign of Aggregation): When particles are separated by long
distances, (1000 to 2000 Angstroms), particles form aggregates because of attraction
again. This is used in controlled flocculation of coarse dispersions.
Lyophilic Colloids:
Stability depends on electric charge and Hydration.
Coagulation of Lyophilic colloids occur because :-
(a) Addition of excess electrolytes:
The precipitating power of an Ion is directly related to the ability of that ion to
separate Water molecules from the colloidal particles.
Anions: Citrates > Tartrates > Sulfates > Acetates > Chlorides > Nitrates >
Bromides > Iodides
Cations: Mg2+ > Ca2+ > Ba2+ > Na+ > K+
(b) Addition of oppositely charged colloids: results in flocculation.
(c) Addition of Non solvent: because of dehydration. Eg. Alcohol in Water results
in precipitation of hydrophilic colloids.

Dr Prakash Katakam
Sensitization:
If a very small amount of hydrophilic colloid is added to a hydrophobic colloid,
adsorption takes place, then the second one gets sensitive to precipitation when any
electrolyte is added to it.
Protective colloidal action:

When a large amount of Hydrophilic colloid (of opposite Charge) is added to
Hydrophobic colloids, adsorption takes place and the Hydrophobic colloid will not
coagulate and becomes Stable.

Dr Prakash Katakam
Gold Number: is defined as the minimum weight in Milligrams of a Protective

colloid required to prevent a Color change from Red to Violet in 10 ml of Gold Sol on
addition of 1 ml of 10% solution of NaCl.
(Basically gold sol is a hydrophobic colloid and has a Red Color).
Protective colloid Gold Number

Gelatin 0.005 – 0.01
Albumin 0.1
Acacia 0.1 – 0.2
Tragacanth 2
Kinetic properties of colloids

¾ Brownian motion
¾ Diffusion
¾ Sedimentation
¾ Viscosity
Brownian motion:
Colloid particles donot sediment and they are in random motion, because of their
smaller size (upto 5 microns size). The molecular collisions keep particles under
random motion. When particle size increases, the velocity of the particles decreases
and gravitation force starts influencing and settling starts. Brownian movement can be
decreased by increasing viscosity of the liquid, eg. By adding Glycerin.
Diffusion:
The colloids can diffuse through membranes because of their small particle size. This
is used to find out the molecular weight of polymers.
Fick’s First law states that particles diffuse from a region of high concentration to a
region of lower concentration until the diffusion equilibrium is attained. It is used to
find out the Molecular weight.
RT 3 4πN
D= where,
6πη o N 3Mν
D = diffusion coefficient of the polymer (cm2/sec)
R = molar gas constant
ηo = viscosity of dispersion medium
N = Avogadro’s number
M = molecular weight of the polymer
ν = particle specific volume of the particles
Substances with faster diffusion are called as Crystalloids. Eg. Sugar, salts, acids, etc.
Substances with slower diffusion are called as Colloids. Eg. Gelatin, albumin, etc.
Sedimentation
The velocity of sedimentation of spherical particles is obtained by Stoke’s Law. This
law does not applicable because, gravitation does not influence the Sedimentation of
Colloidal particles. Therefore to separate the polymer solutions based on molecular
weight, Forced centrifugation or Ultracentrifugation is used. Eg. Separation of
antibiotics, vaccines, etc.

Dr Prakash Katakam
Viscosity
Viscosity is an expression of the resistance to flow of a system under an applied
stress. Viscosity of colloids is affected by
¾ Shape of the dispersed particles
¾ Affinity of particles to the medium
¾ Type of colloids
¾ Molecular weight of particles
Electric properties of colloids:

Surface Charge or Zeta potential (ζ): Particles possess a charge on their surface.
Electric double layer (solvent) present around the particles. When particles move, this
movable double layer also moves along with the particles. The electric potential
between the movable solvent sheath and the bulk of the solution is called as Zeta
Potential.
ζ = E/v
E = potential gradient across particles, volts
v = velocity of particles, cm/sec
Electorkinetic phenomena:
The interface: aa’ = solid-liquid interface. The cations (+ve charge ions) from the
solution migrate to solid surface and bind on it. The +ve ions are called as Potential
Determining Ions.
Tightly bound layer: (aa’ to bb’). Here more +ve ions are present. These Anions (–ve
ions) are called as Counter Ions or Gegenions.
Diffuse second layer: (bb’ to cc’): Here more –ve ions are present. After cc’ the ions
are in equal and uniform. The entire system is therefore, electrically neutral.
Therefore the Electric Double Layer consists of
¾ Tightly bound layer and Diffuse second layer

Dr Prakash Katakam
Nernst Potential: It is the potential difference observed between the Solid Surface,
aa’ and electroneutral region of the solution.
Zeta potential: It is the potential difference between the Shear plane (tightly bound
layer, bb’ line) and electroneutral region of the solution.
If Zeta potential is reduced, the attractive forces exceed the repulsive forces and
aggregation takes place. It decreases when more electrolytes are added.
Donnan membrane equilibrium:

Used to enhance the absorption of drugs. A solution of NaCl (Na+, Cl-) is placed on
one side of semi-permeable membrane. On the other side, a solution of negatively
charged colloid (R-) along with its counter ions (Na+) is placed. Volume on two sides
is same.
Initial state: Outside (o) Inside (i)
|
+
Na | R-
-
Cl | Na+
|
Na+ and Cl- ions move freely across the membrane but colloidal particles, R-, cannot
and Equilibrium is attained soon.
At equilibrium: Outside (o) Inside (i)
|
+
Na | R-
Cl- | Na+
| Cl-
Apply the condition of Electroneutrality:

Outside: [Na+]o = [Cl-]o
Inside : [Na+]i = [R-]i + [Cl-]i
According to principle of escaping tendency, the concentration of electrolytes on both

sides of the membrane must be same.
[Na+]o [Cl-]o = [Na+]i [Cl-]i
Upon substitution we get, Donnan membrane Equilibrium Equation as follows:
[Cl − ]o [ R − ]i
−
= 1+
[Cl ]i [Cl − ]i
This equation is used to enhance the absorption of drugs. Eg. Sodium CMC is used to
enhance the absorption of Sodium Salicylate.

Dr Prakash Katakam
SAMPLE QUESTIONS
1. Calculate the equivalent weight of NaOH, if the atomic weight of NaOH is 40.
2. How to prepare 0.5 N H2SO4 solution of 2 liters? The equivalent weight of H2SO4
is 49.
3. A solution contains 2 milliequivalents of calcium (Ca++) per 100 ml. Calculate the
Strength of Ca++ in terms of mg/L and gm/L? The equivalent weight of Ca++ is
20.
4. Define True Solution.
5. Define a Phase. What are the different types of phases?
6. Differentiate between Coarse dispersions and Colloidal dispersions with
examples.
7. Define Saturated solution.
8. Define solubility as per united states pharmacopoeia.
9. Define the following terms: Molarity, Normality, %w/w and %w/v.
10. Define the following terms used in pharmacy: Very soluble, slightly soluble,
sparingly soluble and practically insoluble.
11. What are the basic principles of solubility?
12. The solubility of liquids in liquids is called as ______________________.
13. Mention the factors influencing the solubility.
14. What is salting-out effect?
15. If a foreign substance is added to a Binary Liquid System, it produces 3
component system. Discuss the influence of the foreign substance with examples.
16. What is the influence of Dielectric Constant on the solubility of a substance?
17. Define Ideal Solutions. Write the thermodynamics formula for Ideal solution of a
solid in a liquid.
18. Define Non-Ideal solutions. Write the formula for Activity constant.
19. With the help of a Figure, explain the steps involved in the solubility mechanism.
20. Solubility parameters express the cohesion between the like molecules. Write the
equation to calculate Solubility parameter using Internal Pressure.
21. Write the equation used in extended Hildebrand solubility approach.
22. Differentiate the Endothermic and Exothermic process of solubility with
examples.
23. Define solubility product Ksp.
24. Benzoic acid + NaOH ---Æ _______________________ + water,
then +HCl------Æ_____________________ + NaCl
25. Caffeine + Citric acid ------Æ _____________________,
then + NaOH------Æ _____________________ + Na Citrate
26. What happens when pH is reduced for a soluble weakly acidic drug solution?
27. What happens when pH is increased for a soluble weakly basic drug solution?
28. Give the formula to calculate optimum pH required for weak acids.
29. Define Cosolvency? Give two examples.
30. What is the influence of particle size on the solubility?
31. The properties of solutions are (a)__________________________
(b)________________________ (c)___________________________
32. What are the different colligative properties of solutions.
33. The solutes are divided into 2 classes, Electrolytes and Non electrolytes. Define
these terms with examples.
34. Define Osmosis. What is the difference between diffusion and osmosis.

Dr Prakash Katakam
35. Explain the process of osmosis with the help of a neat Diagram.
36. Explain the principle of Osmometer with the help of a neat Diagram.
37. The molecular weight of solute can be determined using
(a)_____________________ , (b)__________________________________
(c)___________________________________
38. The molecular weight of Solute M2 is calculated by the following formula.
w M p0
M 2 = 2 1 1 , Explain the terms in the formula.
w1 Δp
39. The molecular weight of high molecular weight polymers are determined by using
_________________________method.
40. The molecular weight of nonvolatile substances can be determined by
_________________________________method.
41. Cryoscopic method is used especially for ____________________substances like
_______________________.
42. Calculations or Problems based on Theory:
i. Normality
ii. Molarity
iii. Mole fraction
iv. Mole percent
v. Percentage calculations
vi. Milli equivalents

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Dr Prakash Katakam

Faculty of Pharmacy, 7th April University, Zawia, Libya

Dimensions and Units

Dimension = Measurable quantity

Each of these properties is assigned a definite unit. A reference standard is a

Table: Fundamental Dimensions and Units:

Dimension Symbol CGS unit SI unit

• Dimension = Measurable quantity

Derived Dimensions and Units

Derived Dimensional CGS unit SI unit

PHYSICAL PHARMACY, 1 I Year B. Pharmacy

Statistical Analysis of Errors

Errors may be defined as a deviation from the absolute value.

Arithmetic Mean: The Arithmetic mean X is obtained by adding together the

Mean Error = Simple arithmetic mean – True Value

Relative Error (%) = Mean Error x 100

Relative Error is generally Expressed as a Percentage (%).

PHYSICAL PHARMACY, 2 I Year B. Pharmacy

Two types of errors are present. They are

They are usually present in each measurement an affect all observations of a

Errors must be eliminated as far as possible.

PHYSICAL PHARMACY, 3 I Year B. Pharmacy

SOLUTION AND SOLUBILITY

True Solution: is defined as a mixture of two or more components that form a

A solution composed of only two substances is known as Binary solution, and

System: is a bounded space or definite quantity of substance. Eg. Magnetic Field,

Phase: is defined as a distinct homogeneous part of a system separated by definite

Phase: is two types : Homogeneous and Heterogeneous Phase

Homogeneous: One Phase, Eg. Sugar solution

Heterogeneous: More than one Phase, Eg. Emulsion and suspension

Coarse Dispersions: Particle Size 0.1mm (100Å or 10-5 cm) :

Colloidal Dispersions: Particle size very small, 10 to 5000 Å.

Unsaturated solution: Solute concentration is below saturation at a given

Supersaturated solution: Solute concentration is above saturation concentration at a

PHYSICAL PHARMACY, 4 I Year B. Pharmacy

U.S.Pharmacopoeia and National Formulary (USP-NF): defines solubility as the

Solubility Expressions or Concentration Expressions:

For substances not having definite solubility the Terms of Approximate

Principles of Solubility: Solubility of solute in solvent depends on following

PHYSICAL PHARMACY, 5 I Year B. Pharmacy

SOLUBILITY OF LIQUIDS IN LIQUIDS (MISCIBILITY):

Complete Miscibility: Mix in all proportions (any %).

Influence of Foreign Substances: Addition of a substance to a Binary (2-phase)

Effect of Dielectric Constant: As dielectric constant increases, the solubility also

PHYSICAL PHARMACY, 6 I Year B. Pharmacy

Dielectric Solvent Solute

Å--------Decreasing Water Solubility-----

Solubility of Non-ionic Solids in liquids:

The solubility of solid in an ideal solution depends on temperature, melting point of

ΔHf = molar heat of fusion

PHYSICAL PHARMACY, 7 I Year B. Pharmacy

The molar heat of fusion is determined by differential scanning calorimetry.

Drugs ΔHf (cal/mole)

The activity of a solute in a solution = concentration X activity coefficient

In Ideal solution, a2 = X 2i , since γ 2 =1

PHYSICAL PHARMACY, 8 I Year B. Pharmacy

Three steps are involved in the solubility mechanism.

Total work involved in the above interaction = w22 + w11 – 2w12.

Solubility Parameters: (Hildebrand)

ΔH v = the heat of vaporization

PHYSICAL PHARMACY, 9 I Year B. Pharmacy

Extended Hildebrand Solubility (EHS) Approach:

The solubility equation used in EHS approach is

− log X 2 = − log X 2i + A( w11 + w22 − w12 )