Seminar

on
Solubilization
Swami Ramanand teerth Marathwada University, Nanded.
School of Pharmacy

BY
GAJANAN V NAIK
M PHARM IST YEAR ( IIND SEM )
PHARMACEUTICS
Contents

What is solubility & solubility expressions ?

Importance of solubility & Problems with poor
solubility.
What is solubilization?
Process of solubilization.
Methods of increasing solubility.
What is solubility & solubility 1

expressions ?
Description Parts of solvent
Solubility :- required for one part
In quantitative terms - as the concentration of of solute
solute in a saturated solution at a certain Very soluble <1
temperature.
Freely 1 - 10
In a qualitative way, it can be defined as the soluble
spontaneous interaction of two or more Soluble 10 - 30
substances to form a homogeneous molecular
Sparingly 30 - 100
dispersion. soluble
Solubility expressions:- Slightly 100 - 1000
soluble
The solubility of a drug may be expressed in a
number of ways. The United States Pharmacopeia Very slightly 1000 - 10,000
(USP) describes the solubility of drugs as parts of soluble
solvent required for one part solute. Insoluble > 10,000
Importance of solubility & 2

Problems with poor solubility?

Importance: -
It is an important parameter to achieve desired concentration in
systemic circulation.
Solubility behavior of the drug is a one of the important aspects of
preformulation testing for poorly soluble drug
Problems with poor solubility: -
Reduced drug efficiency
Reduced absorption of drug
May cause side effects
What is solubilization? 3

Solubilization:
It can be defined as the preparation of a thermodynamically stable
isotropic solution of a substance normally insoluble or very slightly
soluble in a given solvent by the addition of component or
components or by any suitable methods.

Eg.
Process of solubilization 4

Process of solubilization:-
A. Breaking of inter-ionic or intermolecular bonds in the solute
B. Separation of solvent molecules to provide space for the solute
C. Interaction between the solvent and solute molecule or ion

A. Breaking of inter-ionic or intermolecular bonds in the

solute
Process of solubilization 5

B. Separation of solvent molecules to provide space for the solute

C. Interaction between the solvent and solute molecule or ion

Methods of increasing 6

solubility.
Methods of solubilization.
Addition of co-solvent
pH change method
Reduction of particle size
Temperature change method
Hydro-trophy
Addition of Surfactant
Complexation
Solid dispersion
Polymorphism
Other techniques
Methods of increasing 7

solubility.
Addition of co-solvent
Substances like weak electrolytes and non-polar molecules are poorly
soluble in water.
The solubility of these substances can be enhanced by the addition
of water miscible solvents in which the drug has good solubility. This
process of improving solubility is called as co-solvency and the
solvents used are known as co-solvents.
This technique is mainly used in the formulation of parenterals.
Commonly used co-solvents are Ethanol, Sorbitol, Glycerin,
Polyethylene glycol, propylene glycol etc.
E.g. solubility of diazepam can be increased by using 10%ethanol
and 40% propylene glycol.
Methods of increasing 8

solubility.
pH change method
Most of drugs are weak acids or weak bases i.e. weak electrolytes.
In aqueous medium they dissociate poorly and un-dissociated portion
is insoluble.
So, solubility of the un-dissociated portion is improved by pH control.
For weak acidic drug (Phenytoin, ethosuximide ):- increase pH,
solubility is increase.
For weak base drug (caffeine, theophylline ) :- decrease pH, increase
solubility.
Methods of increasing 9

solubility.
Reduction of particle size
Reduction in Particle size improve solubility of drug.
Basically reduction in particle size increase contact surface area of the
particle, there by ultimately it increase rate of solubility of drug.
Temperature change method
When a mole of solute is dissolved in a large quantity of solvent, then heat is
exchanged with surrounding such exchange is termed as Heat of solution.
Most of the substances are endothermic, absorbing heat in the process of
dissolution. For these substances, an increase in temperature results in an
increase in solubility.
Exothermic substances give off heat in the process of dissolution. The
solubility of such substances would decrease with increase in temperature
Methods of increasing 10

solubility.
Hydro-trophy
Hydro-trophy Addition of large amount of a second solute results in
an increase in the aqueous solubility of another solute.
Solubilization of Benzoic acid with Sodium benzoate.
Methods of increasing 11

solubility.
Addition of Surfactant
Surfactants are molecules with well defined polar and non-polar
region that allow them to aggregate in solution to form micelles.
Micelles are formed at CMC.
Surfactants act by reducing the surface tension.
Ability of a surfactant solution to dissolve or solubilise water
insoluble materials starts at CMC and with increase in conc. of
micelles increases solubility.
Methods of increasing 12

solubility.
Complexation
For the Complexation occur both drug and ligand molecule should be able
to donate or accept electrons.
The solubility of compound is the sum of solubility of the compound and its
complex.
It is reversible association of a substrate and ligand molecule.
The most common complexing ligands are cyclodextrins, caffeine, urea.
cyclodextrins are unique since they increase the water solubility of poorly
soluble drugs by fitting them into the hydrophobic cavity of the
cyclodextrins molecule.
These cyclodextrins have the ability to form molecular inclusion complexes
with hydrophobic drugs having poor aqueous solubility.
Methods of increasing 13

solubility.
Solid dispersion
Solid dispersion technique It is the dispersion of one or more active ingredients
in an inert carrier or matrix in solid state prepared by fusion or melting-solvent
method. It is the dispersion of a drug or drugs in solid diluent or diluents.
Solid dispersions may also be called solid state dispersions.
Various systems of solid dispersions:
Simple eutectic mixtures
Solid solutions
Glass solution and glass suspension
Amorphous precipitation of drug in crystalline carrier
Compound or complex formation between drug and carrier
Any combination among the above
Methods of increasing 14

solubility.
Polymorphism
It is the ability of the compound to crystallize as more than one distinct
crystalline species with different internal lattice.
Different crystalline forms are called polymorphs.
Polymorphs are of 2 types:-
1. Enatiotropic:- e.g. Sulphur 2. Monotropic:- e.g. Glyceryl stearate
Polymorph differ from each other with respect to their physical property
such as
Solubility
Melting point
Density
Hardness
Compression characteristic
Methods of increasing 15

solubility.
Other techniques
Salt formation
Precipitation
Micronization
Nanonization
Supercritical Fluid Recrystallization
Evaporative precipitation into aqueous solution
Use of precipitation inhibitors
Solvent Deposition
Drug derivatization
References 16

The theory & practice of industrial pharmacy by Leon Lachman,

Herbert A. Lieberman, Joseph L. kenig, 3rd edition, published by
Varghese Publishing house, page no:- 171-196.

Martins Physical pharmacy & Pharmaceutical science, 6th edition

by Patrick J. Sinco, Published by Lippincott williams & wilkins,
page no:- 182-183.
 19

Thank you.