Solutions Flashcards
What is dissolution? dissolution rate?
in any process, solids dissolve in a solvent to form solutions. The rate (or time to form a solution) is the dissolution rate)
Why do we study dissolution?
- To show the release of a drug from the tablet is close to 100%
- To show the rate of drug release from is uniform batch to batch
- To show that the release is equivalent to those batches proven to be bioavailable and clinical effective
what is the process of dissolution?
- drug molecules are liberated from surface of particle
- Drug is concentrated in solution at the surface (in contact with solid)
- Solute migrates through the boundary layer to the bulk liquid by diffusion or convection
- Local concentration of a drug decreases as it migrates from the boundary layer
How do we increase the rate of dissolution?
- Increase surface area by crushing - decreases diffusion
- Increase volume of solvent to increase the concentration gradient
- stir to increase d and decrease h
- heat to increase d
what are the factors that affect dissolution described using? what is this?
Notes Whitney equation
dm/dt = D.A. (Cs - C) / h
what is the diffusion coefficient d?
it is used to describe solute molecule movement. for example, from surface to bulk solvent by diffusion
How do molecules move?
By passive diffusion
- By random molecular motions - go from high order to low order
- From regions of high chemical potential (concentration) to a lower one i.e molecules move under a concentration gradient
- 2nd law of thermodynamics - entropy increases wihh time so higher concentration (more order) moves to disorder with a lower concentration
what is the concept of random walk?
Idea that molecules do not cross membranes in straight lines. They take tortuous paths. = molecules move under the influence of Brownian motion. However, overall motion (flux) is in the direction of the concentration gradient.
what is the concept of drug absorption and solubility?
The cell membrane is lipophilic in nature (oil like) - the drug must be soluble in water before crossing the membrane and should also cross the membrane.
what is the pH partitioning hypothesis?
pH - only the unionised form of a molecule crosses the membranes due to higher lipid solubility,
partitioning - molecules cross membranes at a rate dependant on their lipid solubility i.e LogP
what is the henderson hasselbach equation for acids?
pKa = pH + log unionised/ionised
what is the henderson hasselback equation for bases?
pKa = pH + log ionised/unionised
what is the pKA?
The pH at which 50% of the drug is ionised and 50% is unionised.
what is an acid and how do we distinguish ionised/unionised?
Proton donor.
- if pH is 2 units below pKA = it is totally unionised
- if pH is 2 units above pKa = it is totally ionised
what is a base and how do we distinguish ionised/unionised?
proton acceptor.
- If pH is 2 units above pKA = totally unionised
- if pH Is 2 units below pKA = totally ionised
if we have a low pKA - what strength is this base?
Weak base
are acids mainly unionised or ionised in acidic conditions?
unionised
are acids mainly unionised or ionised in basic environments?
ionised
what is the partitioning coefficient log P?
By determining log P of a drug we can assess the tendency of a drug to enter and leave the cell membrane
What is the log P equation?
log p = concentration of same species in organic solvent / concentration of same species in water
in partitioning coefficient - what is the organic phase usually?
n-octanol (oily) - a good mimic of a biological membrane
what if the logP of a molecule is 0?
the molecule equally partitions between aqueous and organic phases.
what are the logP values usually between?
6 and -6
what does a high log P mean?
generally more oil soluble - it does not necessarily mean the drug is very oil soluble - but rather it could mean that it may not be very soluble in either oil or water, or moree soluble in oil than water
What factors affect the solubility of a drug in solution?
- particle size
- melting point and boiling point (solid/liquid)
- molecular size
- nature and position of chemical head group
- temperature
- crystal properties (polymorphic, solvates, amorphous forms)
- pH
What is the passive diffusion ability of -
small non polar hydrophobic molecules
oxygen, nitrogen, benzene cross membranes rapidly
What is the passive diffusion ability of - small uncharged polar
CO2, urea, ethanol, water
cross membranes fairly rapidly
What is the passive diffusion ability of - large polar
glycerol - pass through membranes less readily
What is the passive diffusion ability of - even larger uncharged polar
glucose, sucrose - not really able to pass though membranes
What is the passive diffusion ability of - ions
H+, Na+ etc. Cannot pass through membranes passively
what are polar solvents?
dissolve ionic solutes and polar substances.
ability of the solute to form hydrogen bonds is important i.e they form hydrogen bonds
water dissolve phenols, alcohols, nitrogen, oxygen
electrolytes
hydrophilic electrolytes
what are non polar solvents?
cannot form hydrogen bonds with non electrolytes
dissolve non polar solvents via weak VDW
What are the type of interactions that occur when a solute dissolves in a solvent?
ALL non covlalent e.g. hydrogen bonding, ionic, VDW
