PH2107 - Solutions Flashcards
What is a solution?
Homogenous distribution of individual molecules of a substance dispersed in a solvent
What is a solution comprised of?
- solvent or solvents
- solute
What is a solvent?
that phase in which the distribution occurs
if liquid, referred to as the vehicle solid or semi solid: base
What is a solute?
The component which is dissolved as discrete molecules or ions in the solvent
What appearance may a disperse system have?
The appearance of a solution
What are the two components in a disperse system?
one component is present as small particles or droplets (disperse phase)
the other forms the continuous phase or dispersant
Give examples of solution preparations
IV injection
Infusion liquid solution molecules in a solvent (water or buffer)
Numerous OTC products (cough syrup)
Give examples of disperse preparations
Lotion - calamine lotion Suspension - Calpol Mixture - kaolin and morphine Inhaler - Evohaler Total Parenteral Nutrition (TPN)
What is dissolution?
The process whereby a molecule at the exterior particulate interface is no longer bound (or associated) to other molecules in the particle
What is dissolution characterised by?
Dissolution is a kinetic process, characterised by a dissolution rate
What factors is the dissolution rate determined by?
- association constant (Ka)
- temperature
- free energy of solvation
What increases the tendency to dissolve?
The more similar the solute and the solvent are in polarity, the greater the tendency to dissolve
LIKE DISSOLVES LIKE
What are batches of synthetic drug produced as?
Large solid structures
Describe a crystalline structure
Has a defined structure, arranged in a regular, periodic manner
Describe an amorphous structure
Lacks any defined structure
What does post synthesis milling reduce solid drug structures down to?
A finely powdered particles
What is a particulate?
Particles in the range < 1um
What are forces that bind two adjacent molecules together overcome by?
Attractive forces between molecules of solvent
What happens when a solute molecule is freed from its crystal or other particle?
It becomes solvated within a solvation shell
How do solvent molecules orientate themselves around a solute?
In a complementary manner
- solvent delta- towards delta+ of solute
What happens to a solvation shell when more solvent is added to a solution?
A less strong, outer shell is formed
Eventually, how will the solute and solvation shells exist?
In a ‘sea’ of free/bulk solvent molecules
What is caused when the association of solvent molecules is very strong?
Permanently bound water
How is permanently bound water removed?
Cannot be removed without breaking down molecule
What is a dissociation constant, Kd?
A specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt separates into its component ions
What is the equation for Kd in a pure crystal?
AA A + A
What is the equation for Kd in a non pure crystal (e.g. salt or formulation)?
AxBy xA + yB
How can dissolution be accelerated?
Heat input: Higher temperature increases Brownian
motion causing greater collision between solvent
molecules and molecules at crystal surface
High shear: vortex mixing increases
Interaction between solvent molecules
and crystal
Ultrasonication: ultrasonic waves pass
through crystal, transmitted through water,
physically causes them to shake apart and
interact with solvent faster
How does heat input accelerate dissolution?
Higher temperatures increases Brownian motion causing greater collision between solvent molecules and molecules at crystal surface
How does high shear accelerate dissolution?
Vortex mixing increases interaction between solvent molecules and crystal
How does ultrasonification accelerate dissolution?
Ultrasonic waves pass through the crystal, transmitted through water, physically causes them to shake apart and interact with the solvent faster
What is solubility?
The amount of a substance (mass or moles) that will dissolve in a specific volume of solvent, Csol
How is solubility determined?
- Excess solid drug added to solvent until no more dissolves, at a specific temperature
- Separate excess (centrifugation)
- Analyse supernatant (UV or HPLC)
- Often, very large dilution of supernatant necessary (e.g. x 1000)
- Replication > x3
- Typical data form
- mg/mL
- mol/L - For precision purposes, always accompanied by SD or SEM
What does ‘high solubility’ or ‘poor solubility’ mean?
Not much! It depends on your frame of reference
Which factor is solubility highly dependent?
Temperature
- higher temperature = higher solubility
Solubility should have associated temperature
What is a saturated solution?
The point at which the solution has reached the solubility point
- immediately prior to drug precipitation
- at which no more drug can be solvated
Why is solubility important?
The first step in preparing a formulation is to dissolve the drug in an appropriate solvent
- drugs in solid phase cannot penetrate biological membranes
What state must a drug be in before transport and absorption?
The drug substance must be in solution
The higher the concentration, the higher the . . .
- dose, hence pharmacological effect
- chemical potential (tendency to migrate from high to low concentration)
What factor affects the rate of migration?
The higher the difference in chemical potential, the greater the concentration gradient
What is solvent polarity determined by?
Dielectric constant
What features of a drug affect its solubility?
Molecular features (moieties) broadly described as polar or non-polar
What are the features of alkyl regions?
Don’t ionise
Non-polar
Lipophilic
What is the relationship between alkyl regions and lipophilicity?
The greater the extent of alkyl regions, the greater the lipophilicity
What do functional groups introduce into the molecule?
Varying levels of polarity and LogP values
What effect does the ionic state of ionisable functional groups have?
The molecule’s hydrophilicity or lipophilicity
How do charged drugs exist?
They cannot exist on their own - they must exist as salts
Which drugs need to be lipophilic to be effective?
Drugs for topical delivery to the skin
What is a salt?
An ion and a counterion
What effect can the counterion have?
- ion pair association constant (not too strong)
- toxicity levels of counterion in formulation
- counterion interaction with excipients / packaging (e.g. Cl- is corrosive)
- lability of drug to acid used to make the salt
What is crystallisation?
The converse of solubilisation
- crystal purity desired
What is a polymorphic structure?
When more than 1 crystal lattice forms simultaneously
What effect does shear force in milling have?
Can alter crystal purity
