Phy.

Pharmacy
Chapter 5 - Solubility

Name: Princess Julienne Y. Yu Yr./Sec. 2G-PH Seat no. #43 Date: August 29, 2020

Fill in the blank:

1. Solubility - the concentration of a solute when the solvent has dissolved all the solute that it
can at a given temperature.
2. Solubility- the concentration of solute in a saturated solution at equilibrium.
3. Miscible – a term used when the solute is a liquid and will form a solution with a solvent.
4. The principal factor that influences the equilibrium solubility is the temperature.
5. Heat of the solution - is the overall exchange of energy involved when solute and solvent
molecules come in contact with each other to form a solution.
6. Effect of temperature change on the solubility of the drug, if the heat of solution is:
A) positive (+∆H) – Increase temp. of solvent, increase solubility of drug
B) negative (-∆H) – Increase temp. of solvent, decrease solubility of drug
7. If the heat of solution is positive, heat must be at a higher temperature for the solute to
dissolve.
8. If the heat of solution is negative, heat must be released for the solute to dissolve.
9. The chemical structure of a drug influences its solubility in terms of:
A) Substance with high dipole moment are more soluble in polar solvents such as water
because of its charge distribution and orientation.
B) Dielectric properties – relate to the ability to store charge. This can influence how a
substance interacts with solvents such as water
Substance with charges can interact with the partial charges of water to have good
solubility.
C) Hydrogen Bonding – is an important component of solubility because of the formation of
the intermolecular forces that holds a substance in solution. Any compound with
functional group such as OH, NH and SH can hydrogen bond and be attracted to water,
and can therefore increase the drug molecule’s water solubility.

10. Micronization - is a process of increasing the solubility of a drug by breaking the bonds in the
crystal lattice.
11. Micronization will reduce the energy required to separate the solute from itself consequently
increasing solubility or rate of dissolution of drugs.
12. General Solubility Rules
A) Like dissolves like. -
Polar substances WILL dissolve in polar substances Non-polar
substances WILL dissolve in non-polar substances Non-polar
substances WILL NOT dissolve in non-polar substances.
 B) Solubility in water is increased by increasing the capacity of the solute of hydrogen
bonding with polar groups.
C) Solubility in water is decreased with increase in molecular weight without increasing
polarity. Solubility in water is decreased with increase in the number of carbon atoms in
the solute.
D) For many organic molecules, a high melting point means (high or low) low water solubility.
E) Cis (z) isomer is (more or less) more soluble than trans (e) isomer because cis has (higher
or lower) lower melting point and the repulsive force of the molecules are (farther or
nearer) nearer from each other.
F) Increasing unsaturation increase solubility in polar solvents.
G) Anhydrous solutes are (more or less) more soluble than are those that are crystalline.

13. Solubility product constant (Ksp) – a constant which is equal to the product of the equilibrium
concentration of dissolved ions of a salt, with each ion raised to its stoichiometric coefficient.

14. A) Weak acids (HA)– dissociate partially in water to give hydrogen ions (H +) and weak acid ions
(A-) in equilibrium.
Weak bases (B)- react with water to take on a proton and become the associated weak
base (BH+) and give hydroxide ion(OH-) in equilibrium

B) Weak acids – increase in pH (decrease in H+), increase in solubility

decrease in pH (increase in H+), decrease in solubility
Weak bases - increase in pH (decrease in H+), decrease in solubility
decrease in pH (increase in H+), increase in solubility

15. 10% phenol in water is an example of a liquid in liquid that is influenced by temperature
because its preparation is not possible at 25⁰C but when it is warmed slightly to 37⁰C, it
becomes a solution. temperature influences the solubility of a liquid in another liquid, and the
limit of miscibility changes.

16. The solvents that can best dissolve:

A) strong electrolytes - water
B) weak electrolytes - co-solvents or mixed solvents, such as alcohol, Propylene glycol and
polyethylene glycol
C) nonelectrolytes – organic solvents, little or no solubility in water
17. Dissolution - the process by which a solid solute enters into a solution in the presence of a
solvent
18. The basis of the dissolution of particles in:
A) Diffusion Layer Model – concentration gradient between concentration of the drug in the diffusion
layer (Cs) and concentration of the drug in the bulk medium (C b), (Cs - Cb).
 B) Noyes-Whitney Relationship – the amount of drug dissolved from solid particles is a function of
time
C) Hixson-Crowell Cube-Root Relationship – the size of particles decreases as the drug dissolves
which results to changes in the effective area.

19. The importance of dissolution study:

A) An important quality control test for pharmaceutical products which provides the total
time for release of the drug.
B) Dissolution profile of a drug can be used in the formulation the drug for maximum
bioavailability.

20. Factors affecting dissolution:

Factors Effect on dissolution rate

A. Physicochemical Properties of the rug

d
Ionized vs. non-ionized forms Faster dissolution in aq. media for polar ionized form
compared to the unionized form

Particle size Faster dissolution for smaller particles.

Crystalline state Faster dissolution for amorphous form

B. Formulation Factors

Solid dosage form Dissolution is accelerated by disintegration and

disaggregation which exposed the individual drug
particles to the dissolution medium

Suspension and emulsion
An increase in particle size upon settling and aggregation
will decrease dissolution rate.
Change in the crystalline structure of the drug particles in
aged suspensions tend to dissolve slowly. Dissolution rate
decreases with increasing viscosity of suspensions.

Semisolid Dosage Forms Dissolution characteristics of the drug are dependent on

the type of base used.

C. Physiologic Factors

Gastric emptying time and Gastric emptying time can have a marked effect on how
Intestinal Transit Times much of the drug will dissolve before it moves to the GI
tract. Normal GET- 1-4 hours.
GET is shorter during fasted than fed state.
 Variability of pH Weakly basic drugs tend to dissolve better in the stomach
(pH 1.5-3.0) where more drugs will be ionized.
Weakly acidic drugs tend to dissolve better in the upper
intestine (pH 5.0-7.0)

21. Partition Law 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.
22. Drug’s Partition Coefficient is a measure of a drug concentration in a non-polar organic phase
to that in a polar aqueous phase.
23. Partitioning orientation of the following solutes.
A) Strong electrolytes –aqueous layer
B) Nonelectrolytes – both aqueous and organic solvent
C) Weak electrolytes – depends on pH of solution