Lecture 16 - drug solubility and dissolution rate 1 Flashcards
Give the organs in the GI tract.
Two ways in which an aqueous solution may be absorbed.
- Aqueous solution –> straight into GI fluids –> absorbed
OR - Aqueous solution –> precipitation –> suspension of fine particles in GI fluids –> solution of drug in GI fluids –> absorption
How does an aqueous suspension get absorbed?
Aqueous suspension –> suspension of fine particles in the GI fluids –> solution of drug in GI fluids –> absorption
How do immediate dosage forms get absorbed?
Immediate release dosage from –> aggregates granules –> suspension of fine particles in GI fluids –> absorption
Drugs already in solution are absorbed much…
faster
Solution
Solution is a molecular dispersion formed by 2 or more components which form a one phase homogenous system
Mixture
A mixture of two or more components that forms a single phase which is homogenous down to the molecular level
Solvent
the component that determines the phase of the solution is the solvent. The solvent is the largest proportion of the system
Solutes
the other components of the solution. Are dispersed as molecules or ions throughout the solvent- dissolved in the solvent
Saturated solution
solute is in equilibrium with the solid phase
Solubility - in quantitative terms - give two definitions.
the concentration of solute in a saturated solution at a certain temperature. OR The maximum mass or volume of solute that will dissolve in a given mass or volume of solvent at a particular temperature
Solubility - qualitative
the spontaneous interaction of two or more substances to form a homogenous molecular dispersion
Unsaturated solution
the dissolved solute is in concentration below that necessary for complete saturation at a definite temperature
Supersaturated solution
contains more of the dissolved solute that it would normally contain at a definite temperature. Dissolution of large amounts at an elevated temperature. Upon cooling will fail to crystallize from the solution
solubility can be expressed in terms of molarity and molality. What does that mean?
Molarity- number of moles of any compound per litre
Molality = number of moles in 1kg of solvent.
The BCS classifies drugs according to solubility and permeability. Give the four classes.
Class one- high solubility/high permeability
Class two – low solubility/ high permeability
Class three – high solubility/Low permeability
Class four – high solubility/ high permeability.
define dissolution
describes the process by which drug particles dissolve.
For a drug to be absorbed it must be….
IN SOLUTION
Describe what is going on in this diagram.
- Diffusion layer: during dissolution the drug molecules in the surface layer dissolve to form a saturated solution around the particles
- The dissolved drug molecules then pass through the dissolving fluid to contact absorbing mucosa and are absorbed. The drug eventually enters bloodstream.
The diffusing layer is replenished by further drug dissolution- absorption continues.
The rate of dissolution is determined by the slower step. What is the slowest step in dissolution?
The diffusion of the solute from the saturated solution surrounding the drug particle to the bulk of the solution.
Give Fick’s law equation and label it, in terms of dissolution.
Fick’s law states that the mass transfer of solute molecules through the diffusion layer is directly proportional too…… and inversely proportional to…..
directly proportional to the area available for migration (diffusional surface area) and the change in concentration across the boundary layer.
The rate is inversely proportional to the thickness of diffusion layer
Give Noyes-Whitney equation and label it in reference to dissolution.
The Noyes-Whitney equation states that dissolution rate can be increased by increasing…
the surface area of the drug by reducing particle size, increasing drug solubility in diffusing layer, Increasing K- dissolution rate constant.
Why shouldn’t you crush be tablets and give it to a child?
Increases dissolution rate because the surface area is increased. This can potentially be toxic.
K in the Noyes Whitney equation is the diffusion rate constant. How can it be calculated?
D = the diffusion coefficient of the solute in the solvent. V= the volume of the dissolution medium. h= the thickness of the boundary layer.
If drug dissolution is fast, the rate of absorption of a drug is dependent upon…?
its ability to pass through the absorbing membrane.
If drug dissolution is low, what is the rate limiting step in absorption?
dissolution
Name factors affecting the dissolution rate
A -surface area of solid drug particle
Cs- solubility in the dissolution medium
C - concentration in the bulk of the solution at a given time
D - diffusion coefficient of the solute in the solvent
h - thickness of boundary layer
What can affect the surface area of solid drug particle?
size of particles
porosity
dispersibility
surfactants
What affects solubility in the dissolution medium?
temperature, nature of solvent and solute, pH, crystalline form, presence of other compounds, solubility agents.
Reducing particle size will ……………. dissolution rate. Why?
the reduction of particle size increases dissolution rate. This is because there is an exposure of increasing amounts of solute to the solvent.
Particle size can effect, what?
stability/less stable - penicillin
side effects - nitrofurantoin
How does structure of the solute effect solubility?
- Molecular area, shape, boiling and melting points and functional groups/substituents and their positions can change solubility.
- The use of salt form increases solubility- higher degree of dissociation in water, increased interaction with the solvent, increases solubility.
