This document discusses solubility and distribution phenomena. It covers types of solvents including polar, semi-polar, and non-polar solvents. Semi-polar solvents can increase the solubility of mixtures by acting as intermediate solvents. Non-polar solvents dissolve nonpolar solutes through weak van der Waals forces. The document also discusses the solubility of liquids in liquids, gases in liquids, and solids in liquids. Key points include Henry's law governing gas solubility in liquids, and factors that affect gas solubility such as pressure, temperature, and chemical reactions between the gas and solvent. Examples are provided to demonstrate calculations using Henry's law.

1. Solubility and Distribution
Phenomenon
PHYSICAL PHARMACY II (lec2)
2ND CLASS / PHARMACY COLLEGE
Lecturer: Amina Mudhafar / University of Mosul

2. Types of Solvents
Polar solvents, Semi-polar solvents, Non-polar solvents
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3. Semi-polar solvents, such as ketones and alcohols, can induce a certain degree of
polarity in non-polar solvent molecules.
In fact, semi-polar compounds can act as intermediate solvents to bring about
miscibility of polar and non-polar liquids. Accordingly, acetone increases the
solubility of ether in water. Other examples an intermediate solvent action of alcohol
on water–castor oil mixtures and the action of propylene glycol on increasing the
mutual solubility of water and peppermint oil and of water and benzyl benzoate.
Semi-polar Solvents
water–castor
oil
Ether- water
Water- peppermint
oil
Water–benzyl
benzoate
propylene glycol
acetone alcohol
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4. These solvents have the following properties:-
1. They are unable to reduce the attraction between ions of strong and
weak electrolytes because of low dielectric constant
2. Cannot break the covalent bonds
3. Cannot form hydrogen bonds
Therefore non polar solvents can dissolve the nonpolar solute by weak
Vander Waals and London forces.
Non-polar solvents
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5. • A drug substance administered by any route must possess some
aqueous solubility for systemic absorption and therapeutic
response.
• Poorly soluble compounds (e.g., less than 10 mg/mL aqueous
solubility) may exhibit incomplete, erratic, and/or slow absorption
and thus produce a minimal response at desired dosage.
• Enhanced aqueous solubility may be achieved by preparing
more soluble derivatives of the parent compound, such as salts or
esters, by chemical complexation, or by reducing the drug’s particle
size.
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Drug Solubility

6. Solubility of Liquids in Liquids
Solubility of Gases in Liquids
Solubility of Solids in Liquids
Topics
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7. Frequently, two or more liquids are mixed together in the
preparation of pharmaceutical solutions. For example:
• Alcohol is added to water to form hydro-alcoholic solutions of
various concentrations;
• Volatile oils are mixed with water to form dilute solutions
known as aromatic waters;
• Volatile oils are added to alcohol to yield spirits and elixirs.
Liquid–Liquid systems can be divided into two categories
according to the solubility of the substances in one another:
(a) Complete miscibility (can be mixed and give one phase
system)
(b) Partial miscibility (The miscibility affected by temperature and
conc.)
Solubility of Liquids in Liquids
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8. The addition of substance to a binary liquid system produce a ternary system
(Three component system) If the added material is soluble in only one of the
two components or if its solubility in the two liquids is markedly different,; the
mutual solubility of the liquid pair decreased
E.g. Phenol/water system …..(partially miscible liquids)
Addition of naphthalene  decrease miscibility because it dissolves in phenol
only
Addition of KCl  decrease miscibility because it dissolves in water only
 both naphthalene and KCl cause salting out
Influence of foreign substances on the miscibility of
liquids
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9. Solubility of Gases in Liquids
 Random collision ‫تصادمات‬ allows stronger
solute-solvent to capture (dissolve) the
gas.
 So, the stronger the solute-solvent
interaction, the more readily the gas will
dissolve.
 To increase number of a (capture) we must
increase the number of collisions.
- More moles of gas.
- Smaller volume holding gas.
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10. Described by Henry’s Law:
States that: (At a given temperature, the solubility (S) of a gas in a
liquid is directly proportional to the pressure (P) of the gas above
the liquid).
S α P
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The carbonated beverages
once you pop the top on a
Coke, the external
pressure has been
reduced, and the
solubility of the CO2 goes
down. This is why Coke
goes flat in a short period
of time after opening.
Solubility of Gases in Liquids

12. S α P
S = KH P
S :- Solubility of the dissolved gas in g/L of solvent.
KH:- Proportionality constant, solubility coefficient, or Henry’s constant.
P:- Partial pressure of gas in mmHg or bar of the un-dissolved gas above the
solution.
The partial pressure controls the number of gas molecule collisions with the
surface of the solution.
If the partial pressure is doubled the number of collisions with the surface will
double that is meaning increasing the pressure will increase the amount of
dissolved gas.
Henry's law:-
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Importance of KH value:
KH is inversely proportional to Solubility S
S
S

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Limitations of Henry’s Law:
Not all gases obey Henry’s Law ,
Gases can obey Henry’s Law if:
1. Solubility of gases in liquids should not be too much.
2. The pressure of gas should not be too high.
3. The temperature should not be too low.
4. The gas (solute) should not react chemically with the solvent.
5. The gas should not associate or dissociate in the solution.
Watch video 1 for more explanation

15. Applications of Henry’s Law
1- All the carbonated beverages are bottled under pressure to increase the
solubility of CO2. When the bottle is opened the pressure above the solution
decreases; as a result the solution effervesces ‫يفور‬ and many CO2 bubbles
liberated out.
2- In administration of anesthetic gases, if the partial pressure of anesthetic gas
is increased; the anesthetic solubility increases in blood.
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16. 3- The amount of the dissolved O2 in mountain lakes is less than its amount
in a lake near the sea level due to lower atmospheric pressure at the
mountain.
Applications of Henry’s Law
lower atmospheric pressure
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17. 4. Solutions of Gas in Liquid in Pharmacy
Mainly include :
• Effervescent preparations (tablets,
granules, powders)
• Solvents for pharmaceutical aerosols
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Applications of Henry’s Law

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Effervescent preparations
Effervescent preparations are designed to produce solutions that release carbon
dioxide simultaneously. Usually, they are prepared by compressing the active
ingredients with mixture of sodium bicarbonate and organic acids such as citric
and tartaric acid.

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Effervescent salts are granules or coarse to very coarse powders
containing a medicinal agent in a dry mixture usually composed of
sodium bicarbonate, citric acid, and tartaric acid.
When added to water, the acids and the base react to liberate carbon
dioxide, resulting in effervescence.
The resulting carbonated solution masks undesirable taste of any
medicinal agent.
they are recommended as a clear and palatable solution.
So, they can be prescribed to patients who suffered from swallow
capsules or tablets.
The main advantages of effervescent preparations ( like tablets) are
quick production of solution. Thus, it is faster and better to absorb.
Effervescent preparations

20. Pharmaceutical aerosols
Liquefied gases under pressure in aerosol devices revert to the
gaseous state when the device is activated and the liquid reaches
atmospheric pressure.
The drug is suspended or dissolved
in the liquefied gas (propellant)
and the drug–propellant mixture
is expelled when the device is
Activated.
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Pharmaceutical aerosols

22. Hydrofluoroalkanes (HFAs) now replace chlorofluorocarbon (CFC)
propellants in pressurized metered-dose inhalers because of the ozone-
depleting properties of CFCs (Montreal Protocol 1989).
There is an equilibrium between a liquefied propellant and its vapor and
there is a vapor pressure above the liquid, the value of which is determined
by the propellants used and the presence of dissolved solutes.
The vapor pressure above the aerosol mixture determines the aerosol
droplet size. In metered-dose inhalers, for example, this has an important
influence on the efficiency of deposition in the lungs.
Solvents for pharmaceutical aerosols
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23. The solubility of a gas in liquid depends on, the partial pressure of the gas
over the liquid, temperature, presence of soluble substance or salts and
chemical reaction between gas and solvent
1- Effect of Pressure (pressure of a gas above the solution)
Gases become less soluble as the pressure above the solution is decreased.
Solids and liquids show almost no change in solubility with changes in pressure. But
gases are very dependent on the pressure of the system.
Some gases escape with violence.
Factors affecting the solubility of gas in
liquid
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24. 2- Temperature
Gases become less soluble as the temperature is increased.
(a higher temperature gives the gases particles the energy needed to escape the
solution completely).
Warning: avoid opening the containers
of gaseous solution in warm climates
and under other condition of elevated
temperature and the container should be
immersed in ice or cold water some times
to reduce the temperature.
Factors affecting the solubility of gas in
liquid
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25. 2- Temperature
-Pepsi or any opened container of carbonated beverage if it is
stands for a while at room temperature ;their taste is very flat
since more CO2 escape
-Boiled water is also taste flat because all of O2 has been removed
by heating.
Factors affecting the solubility of gas in
liquid
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26. 3- Salting out
Gases liberated from solutions in which they are dissolved by
introducing of an electrolyte such as NaCl or non-electrolyte
such as sucrose.
The resultant escape of gas is due to the attraction of the salt
ions or the highly polar non-electrolyte for the water molecules.
“Salting out effect can be demonstrated by adding a small
amount of salt or sugar to carbonated solution”
Note:- Salting out can also occur in solution of liquid in liquid
and solid in liquid
Factors affecting the solubility of gas in
liquid
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Watch Video 3

27. 4- Chemical reaction between gas and solvent
Henry's law applies strictly to a gas that only slightly soluble
in a solution and that do not react in any way in the solvent.
HCl, NH3 and CO2 show deviation from Henry's law as a result
of chemical reaction between the gas and the solvent which
results in an increase in the solubility
O2 with low solubility obey Henry's law.
Factors affecting the solubility of gas in
liquid
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28. Examples
Ex1. If 0.016 g of O2 dissolved in 1 liter of water at a temp. of 25°C
and an O2 pressure of 300mmHg .Calculate:-
A/ The solubility coefficient (Show by calculation the units of Kh)
A= 0.0000533 g/L.mmHg
B/ How many grams of O2 can be dissolved in 250 ml of aqueous
solution when the total pressure above the mixture is 760 mmHg ?
The partial pressure O2 is 0.263 atm. and the temp. is 25°C
B = solubility is 0.0107 g/L
=0.002675g/250 ml
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29. Ex2. ‫مطلوب‬A tank filled with water is pressurized with H2O (g)
and H2(g). The total pressure in the tank is 5 bar at 0°C. The
partial pressure of H2O(g) is 0.15 bar.
Find the concentration of H2(g) in the water, knowing that
Henry’s law constant for H2 at 0°C: 7.8*10-4 mol/L.bar
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