Solubility & distribution phenomenon is useful for pharmacy student to understand the concept on solubility & distribution when study the physical pharmacy.

1. Guided By:
Mr. R. V. Kshirsagar
Assistant Professor,
Presented By:
M. D. Birajdar
M.Pharm P’ceutics
1st Semester
School of Pharmacy, S.R.T.M.U.,Nanded
SOLUBILTY AND DISTRIBUTION
PHENOMENA

2. Importance of studying the phenomenon of
solubility
Understanding the phenomenon of solubility helps the
pharmacist to:
1. Select the best solvent for a drug or a mixture of drugs.
2. Overcome problems arising during preparation of
pharmaceutical solutions.
3. Have information about the structure and intermolecular forces
of the drug.
4. Many drugs are formulated as solutions, or added as powder or
solution forms to liquids.
5. Drugs with low aqueous solubility often present problems
related to their formulation and bioavailability.

3. Thermodynamic solubility of drugs
 The thermodynamic solubility of a drug in a solvent is the
maximum amount of the most stable crystalline form that
remains in solution in a given volume of the solvent at a given
temperature and pressure under equilibrium conditions.
The equilibrium involves a balance of the energy of three
interactions against each other:
(1) solvent with solvent
(2) solute with solute
(3) solvent and solute

4. Solubility expressions
 The USP lists the solubility of drugs as: the number of ml of
solvent in which 1g of solute will dissolve.
 E.g. 1g of boric acid dissolves in 18 mL of water, and in 4 mL of
glycerin.
 Substances whose solubility values are not known are described
by the following terms:
Term Parts of solvent required for 1
part of solute
Very soluble Less than 1 part
Freely soluble 1 to 10 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

5. Solvent - Solute Interactions
 In pre - or early formulation, selection of the most suitable
solvent is based on the principle of
“like dissolves like”
 That is, a solute dissolves best in a solvent with similar chemical
properties. Or two substances with similar intermolecular forces
are likely to be soluble in each others
 Polar solutes dissolve in polar solvents. E.g salts & sugar
dissolve in water .
 Non polar solutes dissolve in non polar solvents. Eg. naphtalene
dissolves in benzene.

6. Types of solutions
Solutions of pharmaceutical importance include:
 Gases in liquids
 Liquids in liquids
 Solids in liquids

7. When the pressure above the
solution is released (decreases),
the solubility of the gas
decreases
As the temperature increases the
solubility of gases decreases
Solubility of gases in liquids

8. Solubility of liquids in liquids
 Preparation of pharmaceutical solutions involves mixing of 2 or more
liquids
 Alcohol & water to form hydroalcoholic solutions
 volatile oils & water to form aromatic waters
 volatile oils & alcohols to form spirits , elixirs
Liquid-liquid systems may be divided into 2 categories:
1. Systems showing complete miscibility such as alcohol & water,
glycerin & alcohol, benzene & carbon tetrachloride.
2. Systems showing Partial miscibility as phenol and water; two liquid
layers are formed each containing some of the other liquid in the
dissolved state.
The term miscibility refers to the mutual solubility of the

9. Solubility of solids in liquids
Factors influencing solubility
1- Particle size (surface area) of drug particles
2- Molecular size
3- The boiling point of liquids and the melting point of solids:
4-The influence of substituents
5-Temperature
6-Crystal properties
7- PH

10. Techniques Of Solubility Enhancement
Techniques of solubility enhancement include:
Physical Modification
 Partical size Reduction
 Modification of crystal habit
 Complexation
Chemical Modification
 Change in Ph
 Use of Buffer

11. Other Methods
 Co- Solvency
 Co- Crystalization
 Hydrotrophy
 Solublising agent
 Using Soluble Prodrug

12. Co-solvent effect on solubility
 The presence of a co-solvent can increase the solubility of
hydrophobic organic chemicals
 Co-solvents can completely change the solvation properties of
“water”
The nonelectrolytes and the undissociated molecules of weak
electrolytes more soluble in a mixture of solvents than in one
solvent alone. This phenomenon is known as cosolvency, and the
solvents that, in combination, increase the solubility of the solute
are called cosolvents.

13.  States that a solute will distribute itself between two immiscible
solvents so that the ratio of its concentration in each solvent is
equal to the ratio of its solubility in each one
CO
Kd = ---------
CW
Co= molar conc in organic layer
Cw= molar conc in aqueous layer
Kd= distribution constant, distribution ratio, distribution coefficient, or partition
coefficient
Distribution of Solutes between Immiscible
Solvents

14. 1-Octanol is the most frequently used lipid phase in pharmaceutical
research. This is because:
 It has a polar and non polar region (like a membrane phospholip
 Po/w is fairly easy to measure
 Po/w often correlates well with many biological properties
Xaqueous Xoctanol
P
Partition coefficient P (usually expressed as log10P or logP) is
defined as:
P =
[X]octanol
[X]aqueous
P is a measure of the relative affinity of a molecule for the lipid
and aqueous phases in the absence of ionisation.
Partition coefficients

15. Application
 Extraction
 Preservative action of weak acids in o/w systems
 Drug absorption/distribution/action

16. References:
1. D.M. Brahmankar, Biopharmaceutics and Pharmacokinetics-A
treatise. Vallabh Prakashan. P 27-48.
2. Patrick J. Sinko. Martin’s Physical Pharmacy and Pharmaceutical
Sciences. 6th Edition, p 182-195.
3. Thomas L. Lemke, David A. Williams. Foye’s Principles of
Medicinal Chemistry. 6th Edition. P 210-240.
4. Guidance for the implementation of research. ECHA (European
Chemicals Agency). Version-2.2. August 2013.
5. Chemical Reviews: Partition coefficients and their uses. ALBERT
LEO. Volume 71. Number-6. December 1971.

17. Thank you….