the medicine Flashcards
what is intrinsic the solution rate (IDR)
The rate of dissolution is dependent on mainly variables. For example, particle size, viscosity, pH, temperature.
However, the intrinsic dissolution rate is a measure of dissolution, which is independent to these variables
What are the units for intrinsic dissolution rate?
cm/s
What letter represents the intrinsic dissolution rate
k
what does a larger value of k suggest
A faster dissolution rate
what are the two equations for intrinsic dissolution rate
k = D/h and kCs = dm/dtA
Why are salts important in pharmacy?
improvement in drug solubility may be achieved by forming a salt. It may improve dissolution rate
is the dissolution rate high or low of a weakly acidic drug in a low pH
low
Is the dissolution rate of a weekly acidic drug high or low in a high pH?
high
is the dissolution rate of a weakly basic drug high or low in a high pH?
low
is the dissolution rate of a weakly basic drug high or low at a low pH
high
suggest why a weakly acidic drug is converted to basic salt, then the dissolution of a basic salt forms a weakly acidic drug again (HD)
HD to NaD to HD again
Sodium ions increase the pH of the diffusion layer, allowing the free drug to be more soluble in the diffusion Layer
D- complexes back with hydrogen ions (H+) to form HD again. It’s forms as a fine precipitate of the free acid this decreases particle size and increases surface area. This increases dissolution rate, and the absorption of HD
describe dissolution of an acidic salt of a weakly basic drug in gastric fluids
example [chlopromazine hydrochloride]
hydro chloride ions lower the pH of the diffusion layer, and ensure it is lower than the gastric/intestinal fluids
this increase solubility/dissolution in the diffusion layer
Precipitation of the free base is avoided as absorption into the small intestine is rapid
why is salt choice important in formulation?
can deliberately choose a salt to decrease apparent solubility
for example, formulations with sodium salt can have a bitter taste in solution
Formulations with magnesium salt decreases solubility, therefore less drug is in the solution, and the bitter taste is reduced
What is the common ion effect?
Adding a common ion reduces the apparent solubility of a slightly soluble electrolyte
AB (solid) = B- + A+ (solutions)
increasing the apparent [] of A or B will push equilibrium towards the left, more solid AB will precipitate
what does the Noyes-Whitney equation assume
it assumes a constant surface area of solid during dissolution
we need a dissolution equation for changing surface area what law do we use
Hixson-Crowell cube root law
what is the Hixson-Crowell cube root law
it assumes drug powder consists of un uniformly sized particles
radius of particles is not assumed, constant throughout the dissolution process
Rate of dissolution is based on the cube root of the weight of the particles
what is the Hixson-Crowell cube root law
cube root Mt = cube root Mo -kt
where:
Mt= undissolved mass at time t
Mo= mass at the start
t= time
k= the cube root of the dissolution rate constant
can be y=mx+c
what does -k suggest
that the gradient is negative. and the y intercept is cube root Mo ( mass at the start )
what is salting in
when solubility has increased the effects is referred to as salting in. (hydro trophy)
commonly occurs when salts of organic acids are added
Increasing the amount of salt added, increases the effect
What is hydrotrophy?
salting in
what is more common salting in or salting out?
salting out
what is salting out
when the apparent solubility has decreased
inorganic electrolytes, commonly decrease solubility. ions of electrolytes, interact with water molecules, reducing the amount of water available for dissolution of nonelectrolyte.
The effect is greater with highly saturated electrolytes.
eg: LiCl having a greater effect than CsCl
what is complexation
it may be possible to interact a poorly soluble drug with a soluble material to form a soluble macromolecule complex.
this is a reversible process
eg: I2 + KI = KI3-
what are cyclodextrins
A hollow cylindrical molecule made up to glucose units in a cyclic arrangement.
they have the ability to form inclusion complexes.
They can also be used to improve the rate of dissolution of a drug
What is an inclusion complex?
part of the drug molecule that inserts into the hollow central cavity of the cyclodextrin molecule.
Do exothermic reactions, increase or decrease solubility
Decrease solubility
Do endothermic reactions, increase or decrease solubility
Increase solubility
