State the importance of dissolution
Only substances in the molecularly dispersed form ( in solution ) can be transported across biological membranes to be absorbed into systemic circulation
What influences the rate and extent of dissolution
The excipients
What is the notes - Whitney equation and what does each letter stand for
dm. kA ( Cs - C)
———. =. ——————-
dt. h
dm
———. the dissolution rate
dt
K - diffusion coefficient
A - surface area
Cs - saturation solubility in the diffusion layer
C - concentration of drug in solution
h - thickness of diffusion layer
Because we want the dissolution rate to be large so dissolution is fast
We want diffusion coefficient , surface area and saturation solubility in diffusion layer to be high
And we want concentration of drug in solution and thickness of layer to be small
What factor affects surface area of undissolved solid A
- Particle size
- porosity of solid particle
Smaller particles = bigger surface area
Porous solids have more pores and so a higher surface area
What factor affects Saturation solubility in diffusion layer Cs
- temperature
- salt forms
- molecular structure
- crystalline form polymorphism
- presence of other compounds
Describe how temperature affects Saturation solubility in diffusion layer Cs
Higher temperatures = higher solubility
As kinetic energy of particles increase which encourage faster dissolution
Describe how salt forms Saturation solubility in diffusion layer Cs
Conversion of weak acid to its sodium salt = greater ionic dissociation of compound when dissolved in water = higher solubility
Describe how molecular forms Saturation solubility in diffusion layer Cs
Solutions already in molecular form available for absorption
may contain acidic drugs as salt form which can precipitate in stomach . But precipitate usually dissolved easily in smalll intestine
Poorly water soluble acidic drugs may have better bioavailability as a suspension.
Suspensions almost as efficient as solutions.
Typically poor water soluble drugs show dissolution rate - limited absorption
What factor affects concentration of drug in solution C
Volume of dissolution medium
If we increase the volume the concentration will decrease
What factor affects Diffusion coefficient K
Viscosity of the medium
Less viscous ( thinner ) = less resistance more dissolution
What factor affects Thickness of the diffusion layer h
Degree of agitation of medium
Increasing agitation reduces thickness
Describe how polymorphism / crystalline forms affect saturation solubility im diffusion layer
Crystalline - molecules are packed in defined order which repeats each form is known as a polymorph which will affect C
Amorphous forms generally have higher solubility than crystalline forms
Anhydrous form often has a higher dissolution rate than hydrous
What is the role of common excipients in tablets for oral use
Disintegrant - ensures tablet breaks into fragments when in contact with liquid . Works by increasing water uptake / rupturing t valet by swelling.
E.g starch and cellulose
Will increase A
Dissolution enhancer - temporarily increases solubility during dissolution.
What is the role of common excipients in injections for parenteral drug delivery
- Vehicle e.g water or common console vents e.g alcohols
Sometimes oily vehicles e.g esters to provide a depot of drug for slower absorption
W
- buffers to adjust pH
Preservatives to increase stability
What is the role of common excipients in vaginal suppositories ( pessaries ) for vaginal drug delivery
Pessaries contain 1/more active substances dissolved / dispersed in a base
Base may be soluble / discernible in water / melt at body temp
Common hydrophobic based
Hydrophilic waxes
Gelatin hydrophilic )
Hydrophilic Bases are water miscible and mix w secretions.
What is the role of common excipients in ointments , creams and pastes for topical and transdermal drug delivery
what is the need for advanced drug delivery with regards to contraception
give zero order release of the drug.
this means an initial rise then constant drug plasma concentration inside the therapeutic window.
this can lead to constant drug effect so a reduced window for unplanned pregnancies to occur
how can constant drug plasma concentration in the therapeutic window be acheived
What are long - acting reversible contraceptives LARCs and give examples
methods of birth control which provide effective contraception for an extended period without requiring user action
e.g IUDs and IUSs
How do IUDs act as a LARC
inserted within the cervical canal and sit in the uterus. no hormones .copper
they impair sperm viability and result in the endometrium being left inhospitable to inplantation of the embryo
give some advantages and disadantages of IUDs
+
no drug interactions
effective immediately
highly effective
reversible
-
can result in menorrhagia
less likely to protect against ectopic pregnancy
How do IUSs act as LARCS
polymer t shaped frame with a hormone resevoir around stem
resevoir contains drug which when released supresses the endometrium preventing implantation
also causes cervical mucus to thicken making it inpenetrable to sperm
Give some advantages and disadvantages of IUSs
+
highly effective
reversible
reduced risk of menorrhagia
-
less likely to protect against ectopic pregancies
irregular bleeding
wider than IUD
what are matrix systems
contain drug loaded uniformly into a polymer matrix .
release is controlled by diffusion through matrix material/ aqueous pores
