W4 Solids, Solutions and Dissolution of Solids

Question 1

When can dissolution occur?
(attraction)

Answer 1

When the attractive force between the drug crystals is greater than the attraction between drug crystal and the solvent molecules

Question 2

What are the 3 steps of dissolution of a crystalline solute?

Answer 2

1. Solute molecule leaves particle
2. Creation of a cavity in the solvent
3. Solute molecule enters the cavity

Question 3

What is the definition of solubility?

Answer 3

Mixture of two or more components that form a single phase that is homogenous to the molecular level

Question 4

What is the definition of a solvent?
(What does it determine?)

Answer 4

– The component which determines the phase
(usually present in the greatest quantity and
often a liquid)

Question 5

What is the definition of a solute?

Answer 5

– The “other” component(s) which are dispersed as molecules or ions throughout the solvent – these components are in solution

Question 6

What is the definition of dissolution?

Answer 6

– The process whereby molecules or ions from the solid phase into solution

Question 7

Is a solution single or two phase?
Are suspensions or emulsions one phase or two-phase

Answer 7

This is single phase
They are two-phase

Question 8

What is a saturated solution?

Answer 8

When an equilibrium is reached and no more solute can dissolve

Question 9

What are solids in liquid? (2 types)

Answer 9

1. Solution of non-electrolytes (non-ionic)
   e.g. organic molecules such as phenol, sucrose
2. Solution of electrolytes (form ions in solution)
   Strong electrolytes (fully ionised over a wide pH range) e.g. NaCl
   Weak electrolytes e.g. weak acids and bases
   (ionisation dependent on pH)

Question 10

What are liquids in liquid?

Answer 10

1. Completely miscible, e.g. ethanol and water
   Miscibility: “mutual solubility of components in
   liquid in liquid systems”
2. Partially miscible, e.g. water and octanol
   Partial miscibility is affected by temperature
   Partially miscible binary liquid mixtures are used
   with a separating funnel to determine partition
   coefficients

Question 11

Gas in liquid:
What is the solubility determined by?

Answer 11

• Solubility of gases is determined by temperature and pressure
• Solubility generally decreases as temperature rises
• Process used in manufacture of Water for Injections BP
• Solubility generally increases as pressure rises

Question 12

What is the pharmaceutical relevance of dissolution?
(for info)

Answer 12

– Drugs usually need to be in (aqueous) solution to be absorbed
– “40% of currently marketed drugs are poorly soluble based on the
definition of the biopharmaceutical classification system (BCS), about 90% of drugs in development can be characterised as poorly soluble”
- Medicine incompatibilities- BNF guidance on intravenous infusions

Question 13

Most drugs have what structure?

Answer 13

Crystalline e.g. Insulin
If such a drug is to enter solution then the individual molecules must leave the crystalline particles

Question 14

What are solute-solvent interactions?

Answer 14

Attractive forces between solute and solvent are governed by the molecular structure of the solid and the nature of the solvent
“Like dissolves like”

Question 15

Can molecular structure have an effect on solubility?
An example?

Answer 15

• A small change in molecular structure, e.g. addition /
  removal of a functional group, can have a marked effect on solubility
• Consider the aqueous solubility of benzene & phenol:* Polar –OH group has a major effect on solubility
  Phenol is >100 times more soluble

Question 16

What has an effect on solubility? (5)

Answer 16

Polar -OH group presence
Salt formation (more soluble)
Isomerism
Substituent position of functional groups
Charged fund groups are more hydrophilic- more soluble

Question 17

Examples of polar solvents
They have a high..?
How do polar solvents dissolve ionic solutes?

Answer 17

water, methanol, acetic acid,
Relative permittivity (dielectric constant)
By reducing the force of attraction between oppositely charged ions in crystalline solids, e.g. sodium bicarbonate
* Polar solvents can even break covalent bonds

Question 18

What are examples of semi-polar solvents?
What can they do?
(Co-solvents)

Answer 18

Acetone, Ethanol, Dimethyl sulfoxide

• Can dissolve polar and non-polar substances
• Solvent molecule dipole moment or H-bonding
  groups enable polar solutes to be dissolved
• Semi-polar solvents can induce a degree of polarity in
  non-polar solvent molecules, e.g. benzene (which is soluble in ethanol)

Question 19

What are non polar solvent examples?

Answer 19

– Alkanes
– Benzene
– Oils and fats

Question 20

What are the features of non-polar solvents?

Answer 20

• Low dielectric constant and lack of H-bonding groups
  prevent these solvents from dissolving ionic or polar
  solutes
• Unable to break covalent bonds
• Dissolve non-polar compounds only
• Non-polar solutes are held in solution through van der
  Waals interactions with the solvent

Question 21

What are some other factors that determine solubility?

Answer 21

• Temperature
• Polymorphism / solvates / hydrates
• Particle size
• pH

Question 22

How does temp affect solubility?

Answer 22

– Dissolution is usually an endothermic process (heat absorbed) so inc in temperature leads to inc in solubility
– If exothermic then the reverse occurs

Question 23

How do polymorphism/solvates/hydrates affect solubility?

Answer 23

– Crystalline solids can exist as different polymorphs depending on
how the constituent molecules are arranged
– Structure also altered by incorporation of solvent molecules
(solvates & hydrates)
– Less stable polymorphs (metastable)
will be more soluble

Question 24

What is the process of diffusion also known as?

Answer 24

Mass transfer

Question 25

How can we speed up the dissolution process?

Answer 25

• Increasing the surface area of the undissolved solid drug(A) increases the dissolution rate
• This can be done by reducing the particle size

Question 26

What is the process of mass transfer(diffusion)?

Answer 26

The boundary layer will soon become “saturated”Saturation of the boundary layer happens almost instantaneously
Solute diffusion from the boundary layer into the
bulk solvent takes more time

Question 27

Noyes-Whitney equation:

What is Cs?
What is C?
What is k1?
What is h?

Answer 27

Cs-Saturated solubility of drug in solvent
C-Concentration of drug in solution at time t
k1-Dissolution rate constant
h- Thickness of boundary layer

Question 28

How can we determine solubility practically?

Answer 28

Empirically or experimentally
Filter or centrifuge (drug and solvent should be as pure as possible)

Then analyse: Plot a calibration curve of Absorbance (Y) vs Drug Conc (X)