W4 Solids, Solutions and Dissolution of Solids Flashcards
Inc lectures: - Solids, solutions and size 1-13 - Solutions - Dissolution of solids (Noyes-Whitney)
When can dissolution occur?
(attraction)
When the attractive force between the drug crystals is greater than the attraction between drug crystal and the solvent molecules
What are the 3 steps of dissolution of a crystalline solute?
- Solute molecule leaves particle
- Creation of a cavity in the solvent
- Solute molecule enters the cavity
What is the definition of solubility?
Mixture of two or more components that form a single phase that is homogenous to the molecular level
What is the definition of a solvent?
(What does it determine?)
– The component which determines the phase
(usually present in the greatest quantity and
often a liquid)
What is the definition of a solute?
– The “other” component(s) which are dispersed as molecules or ions throughout the solvent – these components are in solution
What is the definition of dissolution?
– The process whereby molecules or ions from the solid phase into solution
Is a solution single or two phase?
Are suspensions or emulsions one phase or two-phase
This is single phase
They are two-phase
What is a saturated solution?
When an equilibrium is reached and no more solute can dissolve
What are solids in liquid? (2 types)
- Solution of non-electrolytes (non-ionic)
e.g. organic molecules such as phenol, sucrose - 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)
What are liquids in liquid?
- Completely miscible, e.g. ethanol and water
Miscibility: “mutual solubility of components in
liquid in liquid systems” - 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
Gas in liquid:
What is the solubility determined by?
- 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
What is the pharmaceutical relevance of dissolution?
(for info)
– 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
Most drugs have what structure?
Crystalline e.g. Insulin
If such a drug is to enter solution then the individual molecules must leave the crystalline particles
What are solute-solvent interactions?
Attractive forces between solute and solvent are governed by the molecular structure of the solid and the nature of the solvent
“Like dissolves like”
Can molecular structure have an effect on solubility?
An example?
- 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
What has an effect on solubility? (5)
Polar -OH group presence
Salt formation (more soluble)
Isomerism
Substituent position of functional groups
Charged fund groups are more hydrophilic- more soluble
Examples of polar solvents
They have a high..?
How do polar solvents dissolve ionic solutes?
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
What are examples of semi-polar solvents?
What can they do?
(Co-solvents)
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)
What are non polar solvent examples?
– Alkanes
– Benzene
– Oils and fats
What are the features of non-polar solvents?
- 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
What are some other factors that determine solubility?
- Temperature
- Polymorphism / solvates / hydrates
- Particle size
- pH
How does temp affect solubility?
– Dissolution is usually an endothermic process (heat absorbed) so inc in temperature leads to inc in solubility
– If exothermic then the reverse occurs
How do polymorphism/solvates/hydrates affect solubility?
– 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
What is the process of diffusion also known as?
Mass transfer
How can we speed up the dissolution process?
- Increasing the surface area of the undissolved solid drug(A) increases the dissolution rate
- This can be done by reducing the particle size
What is the process of mass transfer(diffusion)?
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
Noyes-Whitney equation:
What is Cs?
What is C?
What is k1?
What is h?
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
How can we determine solubility practically?
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)
