Biopharmaceutics 2 Flashcards
What is Absolute / Intrinsic Solubility
the maximum amount of of solute dissolved in a solvent under standard conditions of temperature, pressure and pH
it’s a STATIC PROPERTY
What is dissolution?
process where a solid substance enters a solvent to yield a solution
DYNAMIC PROPERTY
Dissolution rate
The amount of drug that goes into solution per UNIT TIME
under standardised conditions of temperature, pH, solvent composition and constant solid surface area
What do we use to measure dissolution
what order of kinetics does it follow
The Noyes Whitney equation
first order
How to we improve the dissolution
Increase the effective surface area (S)
Reduce the thickness of the stagnant diffusion layer (h)
Increase the concentration gradient: Cs should be maximised & the concentration of drug in the bulk (Cb) minimised.
The surface area should be increased to increase the rate of dissolution, why do we do this
This allows more access for water to surround the particles
Motility should be increased to increase rate of dissolution
This takes away the dissolved drug to allow more to be dissolved by water
Stirring speeds up the process and makes a more homogenous mixture
What are sink conditions
The ability of the dissolution media to dissolve at least 3 times the amount of drug that is in your dosage form. Improves robustness and is more physiologically relevant.
How are sink conditions achieved?
Increasing the volume of dissolution fluid
.
Increasing the drug solubility by adding a water miscible solvent to the dissolution media.
Replenishing the dissolution medium constantly with a fresh solvent at specified rate to maintain the drug solubility up to 10-15% of its maximum solubility.
Adding selective adsorbents to remove the dissolved drug.
First order kinetics
Under non sink conditions
Zero order kinetics
under sink conditions
Factors that affect dissolution rate
Surface area of undissolved solid (particle size, porosity, dispersibility)
Polymorphism
Amorphous state
Free acid, free base and salt form
Complexation, solid solutions
Excipients: diluents, surfactants, etc.
Explain drug particle size and effective surface area
Particle size and surface area are inversely proportional to each other.
Higer effective surface area = faster dissolution
What is polymorphism
This is where substances that exists in more than one crystalline form
Stable polymorphs have … energy state, therefore … M.P. and … aqueous solubility.
lower
higher
lower
Metastable polymorphs have
… energy state, … M.P.
and … aqueous solubility.
higher
lower
higher
what is amorphism and what does it represent
The Form of drug which has no internal crystal structure
higher energy state and greater aqueous solubility
Excipients - what are they
inert materials that are added to dosage forms
What do excipients do
✓Improve manufacturability
✓ Improve the appearance, texture
✓ Improve the taste
✓ Improve the bioavailability
The solubility of ionic material is highly dependant
on the pH of the solvent
Ionised compounds or unionised compounds dissolve faster
Ionised
When is a weak acid ionised
When the pH is above the pKa value
E.g. in neutral or basic conditions
A weak acid is unionised
When the pH is below the pKa value
E.g. in acidic conditions
The manufacturing process also affects bioavailability - explain this
Method of granulation, size, density, moisture content, aging of the granules, compression force all affect the dissolution rate characteristics of the tablet.
Method of granulation –
Wet granulation OR Direct compression
