Pharmaceutics Exam 3: Solubility and Distribution

Solubility

Spontaneous interaction of two of more substances to form a homogenous molecular dispersion (qualitative)

- concentration of a solute in saturated solution at a certain temp (quantitative)

What does solubility of a compound depend on?

1. physical and chemical properties of the solute and solvent

2. temperature, pressure, pH

Miscibility

Mutual solubility of components in liquid-liquid system

What does solubility equilibrium involve?

Balance of 3 interactions:

- solvent w solute

- solute w solute

- solvent and solute

What determines thermodynamic solubility?

IMF

- solvent and solute segregated

What needs to happen to move a solute to solution?

Interactions among the lattice energy and cavitation energy must be broken

Lattice energy

Interactions among solute molecules in the crystal

Cavitation Energy

Interactions among solvent molecules in the space required to accommodate the solute

What happens once the solute molecule is surrounded by solvent?

New stabilizing interactions between the solute and solvent are formed

Saturated solution

Solute in solution is in equilibrium with the solid phase

Unsaturated solution

Dissolved solute in a concentration below that necessary for complete saturation

Supersaturated solution

Contains more of the dissolved solute

Expressions of solubility

Solubility of drugs as parts of solvent required for one part solute

Solvent-solute interactions

Solvent molecules arrange themselves around solute molecules

- "like dissolves like"

Polar Solvents

Dissolve ionic solutes such as NaCl, KCl

Ex: Water

Nonpolar solvents

Cannot form hydrogen bridges with nonelectrolytes

- has low dielectric constants

- Ex: hydrocarbons

Semipolar solvents

Can induce a certain degree of polarity in nonpolar solvent molecules

- Ex: Ketone, alcohol, glycerin

Cosolvents

Intermediate solvents to bring about miscibility of polar and nonpolar liquids

Application of Liquid-Liquid Solvents

Two or more liquids are mixed in preparation of pharmaceutical solutions

What are examples of liquids in a liquid liquid system?

1. Alcohol + water = hydroalcoholic solution

2. Volatile oil + water = aromatic water

3. Volatile oil + alcohol = spirits/elixirs

4. Ether + alcohol = collodions

Complete miscibility

Polar and semipolar solvents are completely miscible because they mix in all proprotions

Partial Miscibility

Liquids are miscible in only certain proportions in a temperature-dependent manner

Degree of Freedom

The number of variables that can be changed independently while the system remains at equilibrium

What is the formula for Degree of Freedom?

F = C-P+2

Number of Components (C)

Smallest number of chemical components that are adequate to describe the composition

What factors affect solubility?

1. Temperature

2. pH

3. Solvents

4. Micromeritics

Influence of Temperature on solubility

Heat absorbed = solubility increases

Heat dissolved = solubility decreases

Influence of pH on solubility

Precipitation may occur because the solubility of the unionized species is less than that of the ionized form

The phenomenon in which a solute becomes more soluble in a mixture of solvents than in one solvent is called:

Cosolvency

Influence of Micromeritics on Solubility

Solubility increases with decreasing particle size

Partition coefficient

The ratio of solute concentrations in two immiscible solvents at equilibrium

Application of Partition Coefficient

1. Extraction

2. Preservation of oil

3. Absorption + distribution of drugs throughout the body

Extraction

Determines the efficiency with which one solvent can extract a compound from second solvent

Spear thinning

Shear thinning is when a liquid’s viscosity decreases as the shear rate (stirring, shaking, pumping, or spreading force) increases.

In simpler terms:

The more you stir or shake it, the thinner (less viscous) it becomes — but it thickens back immediately once the force stops.

Thixotropy

Thixotropy is a time-dependent version of shear thinning.

The viscosity decreases gradually under constant shear and takes time to recover once the shear stops.

In simpler terms:

• When stirred or shaken for a while, it becomes thinner.

• Even after stopping, it stays thin for a while before slowly returning to its thick, original state.

Zeta potential

Zeta potential is the electric potential (voltage) at the boundary layer (called the slipping plane) around a charged particle in a liquid.

In other words:

It measures how strongly particles repel or attract each other in a dispersion.