INTRODUCTION: In the past ,the name Physical Pharmacy
was associated with the area of pharmacy that dealt with
the quantitative and theoretical principle of science as they
applied to the practice of pharmacy .Physical Pharmacy
attempted to integrate the factual knowledge of pharmacy
through the development of broad principle of its own ,and
it aided the pharmacist and the pharmaceutical scientist in
their attempt to predict the solubility ,stability ,compatibility
,and biological action of drug products. This remains true
today.
1- BASIC PRINCIPLE:
2- States of Matter: Generally matter can be categorized
into gases ,liquids and solids .A gaseous state
is
characterized by its nature to occupy the compete available
space and changes in volume with respect to the
temperature and pressure .Liquids on the other hand take
the shape of the container in which it is placed .Solids differ
markedly from gases and liquids as they definite shape and
the changes in volume with the variation in temperature
and pressure is very small .A part from the above
mentioned categories some molecules exhibit a fourth
phase termed as mesophase (Greek= meso, middle) which
falls between liquid and crystalline state.
3- Thermodynamics:The word thermodymnamics literally
means flow of heat .However ,the subject is much more
comprehensive
.It
deals
with
the
energy
changes
accompanying all types of physical and chemical process.
Thermodynamics is based on the three generalization or
laws,
called
the
First,
Second
and
third
law
of
thermodynamics. These laws are however based on human
experiences and have never been proved experimentally in
a direct way .The laws of thermodynamics apply only to
macroscopic observable properties of matter such as
pressure, temperature, volume , etc. and not to individual
atoms
or
molecules
.
An
important
concept
in
thermodynamics is the (system).A system is the region of
universe under study .Various types of systems are:
a- Isolated system: matter & energy may not cross the
boundary.
b- Adiabatic System : heat & matter may not cross the
boundary.
c- Closed System : matter may not cross the boundary.
d- Open System: heat, work and matter may cross the
boundary.
1 st law of thermodynamics: (Energy can neither be created
nor destroyed and may be converted from one form to
another), du= q-w ,in which q is the heat absorbed and w is
the work done during the small change of the system.
2nd law of the thermodynamics :(Its impossible to construct
a machine functioning in cycles that can convert heat
completely into the equivalent amount of work without
producing changes elsewhere )
ΔS = q /T , ΔS = the entropy change ,q=heat absorbed
,T=absolute temperature .
3rd law According to this law the probability of entropy of a
pure crystalline substance is zero at absolute zero because
the crystal arrangement must show the greatest orderliness
at this temperature.
ΔS =ƒ Cp /T dT.
4- Determination of the physical Properties of Molecules:
An atom consists of a nucleus ,made up of neutron (neutral
in charge) and proton (positively charged) ,with each
particle carrying a weight of approximately 1g/mol.In
addition ,electron (negatively charged )exist in atomic orbits
surrounding the nucleus and have a significantly lower
weight.
2- EQUILIBRIUM PHENOMENA :
5-Non Electrolytes: Substances whose aqueous solutions
does not conduct electricity are called as non electrolyte is
dissolved, it produces neutral molecules in the solution.
Colligative properties which will be considered are:
1- Lowering of vapour pressure.
2- Elevation of boiling point.
3- Depression in freezing point.
4- Osmotic pressure.
6-Electrolytes Solutions: Substances which when dissolved
in water produce charged particles known as ions.
7- Ionic Equilibria :
Equilibrium can be defined as a balance between two
opposing forces or actions. This statement does not imply
cessation of the opposing reaction, suggesting rather a
dynamic equality between the velocities of the two. Chemical
equilibrium maintains the concentration of the reactants and
products constant. Most chemicals reaction proceeds in both
a forward and reverse direction if the products of the
reaction are not removed as they form. Some reaction
,however ,proceed nearly to completion and ,for practical
purpose ,may be regarded as irreversible .The topic of
chemicals equilibria is concerned with truly reversible
systems and includes reaction such as the ionization of weak
electrolytes.
8-Electromotive Force and Oxidation – Redaction:
An Electrochemical cell consists of two electrodes dipping
either into a common electrolyte or into two different
electrolytes that are in electrical contact with one another
.When it acts as a source of electrical energy ,it is refered to
as a galvanic cell .When it is driven by an external source of
electric current and electrolysis occurs ,it is referred to as an
electrolytic cell. The high resistance voltmeter permits the
potential difference between the Cu and Zn electrodes to be
measured .The limiting value of this electric potential
difference for zero current through the cell (i.e.with the
external load disconnected) is called the electromotive force
(e.m.f),symbol E or Ecell
.In this limiting situation ,a
condition of thermodynamic reversibility exist.
9-Buffers and Isotonic Solutions: Buffer solution are
solution of compounds or mixtures of compounds which
resist changes in their PH upon addition of small quantities
of an acid or alkali .Most buffer solution usually consist of a
mixture of a weak acid and one of its salt or a weak base
and one of its salt. Two solutions are said to be iso-osmotic
or isotonic if they exert the same osmotic pressure when
separated by semi-permeable membrane .Physiologically,
isotonic solution are solution having the same osmotic
pressure as that of the body fluids when separated by a
biological membrane .Body fluids including blood and
lachrymal
fluids
,normally
have
an
osmotic
pressure
corresponding to that of 0.9% solution of sodium chloride
.Thus 0.9% solution of sodium chloride is said to be isotonic
with the physiological fluids .solution with osmotic pressure
lower than that of body fluids or of 0.9% sodium chloride
solution are commonly referred to as being hypotonic and
those having higher osmotic pressure are termed as
hypertonic. Measurement of Tonicity: the tonicity of solutions
may be determined by following methods:
a)- Haemolytic method ,in this method, red blood cells are
suspended in the
solution whose
tonicity is to
be
determined. If the solutions cause shrinkage of the cells,
they are said to be hypotonic. Quantitative measurements
are also possible using this method based on the fact that
hypotonic
solution
librates
oxyhaemoglobin
in
direct
proportion to the number of cell haemolysed.
b)- Colligative methods, it has been determined thst solutions
having same tonicity exhibit similar behavior with respect
their colligative properties such as lowering of vapour
pressure ,depression in freezing point ,etc.
10-
Solubility
and
Distribution
Phenomina:
the
solubility of a substance can be expressed in a number of
ways .Most pharmacopoeia list the solubility of drugs in
terms of the number of parts of solvents required to dissolve
one part of the drug.
11- Complexion and Protein binding:
Complexion may be broadly defined as an association of two
or more species capable of independent .Complexes
generally result from a donor –acceptor mechanism or Lewis
acid –base reaction between two or more different chemical
constitution forming co-ordination compounds .In this, the
donor compound is a non metallic atom or ion ,either free or
contained in a neutral molecules or in an ionic compound
and which can donate an electron pair .The acceptor is
usually a metallic ion or a neutral atom which is capable of
accepting a pair of electrons.
3- KINETIC PHENOMENA:
12-Diffusion: Diffusion is a process which involves the
mass transfer of individual molecules of a substance brought
about by random molecules motion.The study of diffusion is
very important in knowing passage of gasses, drug ,water
vapour through the walls of packing .It also helps in studying
the release of drug entity from the ointments ,gels,
suppository permeation of these molecules through the skin.
This process can be studied by observing the flow of
molecules through a barrier such as a polymeric membrane.
13-Drug release and Dissolution: Dissolution is a
process of mass transfer from the solid into the solvent.
Dissolution rate refers to the rate at which the solid dissolves
in a solvent .When a solid dosage form such as a tablet
begins to pass into solution .Simultaneously, the solid matrix
of the tablet disintegrates into granules and these granules
in turn de aggregate into fine particle .Dissolution of the
drug takes place both from the disintegrated granules and
from the fine particles.
14- BioPharmaceautics : The purpose of this chapter is to
provide the student with a biopharmaceutical foundation for
the study of contemporary pharmaceutical sciences.
15- Chemical Kinetic and stability: Chemical kinetic is
the study of the rate of chemical changes taking place during
reactions .As applied to pharmaceutical formulation ,this
includes a study of the physical and chemical reaction in
drug and dosage forms ,factor influencing the rate of these
chemical reaction ,accelerated stability testing and prediction
of shelf life of formulations.
Rate Constant and Order of Reaction:
According to the law of mass action ,the rate of a chemical
reaction is proportional to the product of the molar
concentration of the reactants each raised to a power usually
equal to the number of molecules ,a and b ,of the
substances A and B undergoing reaction ,
aA + bB
→
Products
Rate = k[A]a [B]b
The order of reaction is the sum of the powers = (a+b).
Molecularity : It is the number of atoms ,molecules or ions
colliding simultaneously to give the products .Unlike the
order of reaction it has only integral values.
Mathematical Treatment:
1- Zero-Order Reaction: As discussed earlier a zero order
reaction proceeds independent of concentration term of the
reactants:
At = Ao – Kot
ko= Ao – At /t
At = Concentration at t=time.
Ao = Concentration at t=zero (initial concentration).
ko = Rate constant (specific rate constant) .
Half life of a Zero-order Reaction;
t0.5 = Ao/2k
Shelf life of a zero order reaction:
t0.9= Ao – 0.9 Ao / k
= 0.1 Ao/k
2- First Order Reaction:
A ————→ Products
a
zero
t=zero
a-x
x
t=time
2.303
a
k=———— log ————
t
(a-x)
Half life of a first order reaction:
t0.5 = 0.693 /k
Shelf life of a first order reaction:
t0.9= 0.1052 /k
3- Second Order Reaction :
A + B ————→ Products
Rate =dx/dt
= k [A] [B]
= (a-x)(b-x)
a)- If the initial concentrations of A and B are equal (a=b) so
the equation can be written as :
Rate =dx/dt = (a-x)2
Or
1
a
kt=——— ———
a
(a-x)
b)- If the initial concentrations of A and B are not equal
(a≠b) :
2.303
b(a-x)
kt=———— log ————
(a-b)
a(b-x)
Half life of a second order reaction:
t0.5 = 1 /ak
Factors Affecting Rate of Reaction:
1- Temperature
2- Light
3- Solvent
4- Ionic Strength
5- Dielectric Constant of Solvent
6- Catalysis
7- Surfactant
4 - DISPERSED SYSTEM:
16- Interfacial Phenomena:
When two phases are in contact with each other ,the
boundary between them is referred to as interface .If one
the two phases is a gas or vapour ,the term surface is
generally used instead of interface .The physical properties
of molecules at the interface are usually different than those
of the molecules in bulk.
Different types of interface are
encountered, depending on whether the two adjacent
phases are solid, liquid or gas .No interface between two gas
phase because they are miscible in all properties.
17-Colloids:
A dispersed system ids defined as a system in which one
phase, the dispersed phase, is distributed uniformly as
particles throughout another phase, called the dispersion
medium or continuous phase. Dispersed system can be
classified on the basis of the physical state of two phases ,
i.e., the dispersed phase and the dispersion medium. Since
matter exist as a gas, liquid and solid, nine different types of
dispersed
systems
are
possible.
Types
of
Colloidal
dispersion:
 Lyophilic Colloids.
 Lyophobic Colloids.
 Association colloids.
18-Coarse Dispersions:
Coarse dispersions differ from colloidal dispersion mainly in
the size of their dispersed particles. While the size of the
dispersed particle in the colloidal dispersion ranges from 1
nm to 1 um ,it is about 1um to 100um in case of coarse
dispersion .suspension and Emulsion are two types of coarse
dispersions.
5- DRUG DELIVERY:
19- Micromertics:
the term micrometrics was given to the science and
technology of small particles by Dalla Valle, Micromertics is
thus the study of the fundamental and derived of individual
as well as a collection of particles.
Importance in pharmacy: The study of particle size and
particle distribution has a number of applications in the field
of pharmacy including the following:
 The rate of dissolution of poorly soluble drugs is
directly related to the size of the drug particles .
 Properties of drug such as rate of absorption and
hence the pharmacological activity depends on the
particle size.
 The release characteristics of drug from ointments,
dcream,and suppositories are dependent on the
particle size of the dispersed drug.
20- Rheology:
21-Biometerial:
22-Drug Delivery: