Sugar is added to purified water and heated until sugar dissolves
Other heat stable components are added
The mixture is cooled and the volume is adjusted to the proper level with purified water
Preparation of Syrups w/out heat
Sugar and other components dissolved in purified water by agitation
volume is adjusted with purified water
more time consuming, good stability
Preparation of Elixirs
Aqueous phase added to alcoholic phase to maintain highest possible alcohol strength at all times to prevent separation of alcohol soluble components
Opium Tincture
only give by drops
Administration of oral liquid dosage forms
teaspoon or tablespoon
calibrated devices
follow with a glass of water
no syrups for diabetic patients
no elixirs with drugs that have antabuse properties
elixir may cause drowsiness
Artificial sweetners
sweeter tgab sycrise
less than 0.2% concentration required
good for use in elixer
saftey concern: Cancer
Advantages of TDDS
avoid GI tract
non-invasive
greater patient compliance
extended therapy
delivery of drugs with short half-life
therapy can be terminated rapidly
Disadvantages of TDDS
Only potent drugs are candidates
Skin irritation
Poor adhesive
Skin structure
Epidermis
Dermis
Sub-cutaneous
Epidermis
major barrier for transdermal drug absorption
5 layers
stratum corneum
primary barrier to drug absorption across the skin
15-20 layers of dead, flattened stacked cornified cells
impermeable and dense
rich in cholesterol, no phospholipids
changes in lipid composition =different permeability
lipid extraction with organic solvents increase permeability
Transdermal drug absorption
transcellular route: drug moves through cells, hydrophilic drugs
paracellular route: drug moves between cells, lipophilic drugs
most drugs use both routes
Intercelluar is the major pathway and barrier
Factors affecting transdermal absorption
physical and chemical properties of the drug
drug concentration
temperature and pH
formulation (liposomes improve absorption)
Exposure time; longer time = greater absorption
Fick's First law of diffusion
dM/dt=AP/\C
dM/dt = total flux transported through a unit area of skin per unit time
A= area of skin
P=permeability coefficient
/\C=drug concentration gradient
Which of the following layers is the primary barrier to drug absorption across the skin?
C. Stratum Corneum
It is generally difficult to get drugs to cross the skin at a sufficient rate (T/F)
True
Epidermis is thicker than dermis (T/F)
False
Which are true about drug epidermal transport?
1. hydrophillic drugs prefer intercellular route
2. most drugs pass the stratum corneum only by intercellular route
3. Intercellular route is also called paracellular route
3
Explain why stratum cornium is the primary barrier for transdermal drug absorption
15-20 layers of dead, flattened, stacked cornified cells
"brick wall" architecture
unique lipids
impermeable and dense
transdermal absorption of most drugs follows Fick's First law of diffusion. Briefly describe the meaning of A, P and /\C.
A= area of skin
P= permeability coefficient
/\C= drug concentration gradient across skin
Effect of hydration on transdermal absorption
increases the penetration of most active compounds
opens up compact structure of stratum corneum
swelling of stratum corneum
apply water to skin or prevent water loss from skin
Chemical penetration enhancers
increase skin permeability by reversible damaging or altering physiochemical nature of the stratum corneum
>275 chemicals
not enhancing enough for macromolecule delivery
Criteria for chemical penetration enhancers
no pharmacological effect
specific in action
reversible action
stable
compatible with components of TDDS
odorless and colorless
inexpensive
Classes of chemical penetration enhancers
extraction of lipids from the stratum corneum
alters the structure of skin lipids, decreasing diffusion resistance
enhances solubility of drug within the skin
loosening of stratum corneum cells (swelling and hydration)
