Parenteral & Transdermal Route of Adminstration Flashcards
Describe the properties of intravenous injections
- usually aqueous buffer at neutral pH
- completely solubilised
- no particles except for some nutritional lipids
- hypertonic solutions are possible with slow administration
What is intramuscular delivery suitable for?
Prolonged release of oily and particulate doses
What is the benefit of higher blood flow in intramuscular drug delivery?
Higher absorption
What are the advantages of subcutaneous drug delivery?
- rapid and predictable
- used for self-medication
- used for poorly absorbed and fragile drugs
What are the uses of intra-peritoneal drug delivery?
Chemotherapy for abdominal tumours, dialysis in renal failure or for diagnostic imaging agents
Give a use for intrathecal drug delivery
Diagnostics - tumours in sub-arachnoid space
Where are intracisternal drugs delivered to and what are the risks?
Space around the base of the brain
There is a risk of neurological injury or death by herniation if intracranial pressure is high
Give uses for intra-ventricular drug delivery
Infection OR to reduce side effects in malignancy
How do needle free injections work?
They force the drug through the skin - they can be spring powered or high pressure gas
How do microneedle patches work?
The stratum corner is pierced with short needles to deliver drugs into the skin with minimal invasion. They increase skin permeability by creating micron-scale pathways in the skin - this actively drives drug through.
Can reach the epidermis too.
What is the dosage range for transdermal formulations?
5-25mg daily
How can transdermal drug penetration be enhanced?
through drug & delivery vehicle modification or through modification of the stratum corneum
Give examples of powered penetration enhancement devices
Iontophoresis
Phonphoresis
Electroporation patches
What are the routes of transdermal penetration?
- Directly across the stratum corneum
- Through sweat ducts
- Through hair follicles and sebaceous glands
What are the properties of the stratum corneum?
- 10-15µm dry
- 40µm hydrated
- layers of keratin rich corneocytes in an intercellular lipid matriculates extruded by keratinocytes
- extruded lipid phase behaviour is different from biomembranes
What is the major route for most drugs?
Intercellular route
Route for drugs soluble in lipid regions or in formulation disrupting the lipid regions
What is the route for most hydrophilic drugs?
Transcellular
Hydrophilic drugs penetrate the aqueous regions of keratin filaments - but also have to go through intercellular lipid region.
What is the ideal molecular weight for a transdermal patch?
<500 Da
but can have <1000 Da
What is the ideal melting point for a transdermal patch?
<200°C
What is the ideal LogP for a transdermal patch?
Between 1 and 3
What is the ideal kinetic half life for a transdermal patch?
<6-8 hours
What is the maximum patch size?
50cm2
How can a drug vehicle be modified to enhance skin permeation?
- Drug selection
- Use of pro-drug
- Ion pairs, complexes
- Modification of chemical potential
- Form a eutectic system
- Use liposomes or vesicles
When would you need to modify the stratum corneum?
If the drug doesn’t have ideal physicochemical properties
How can the stratum corneum be modified to enhance skin permeation?
Hydration
Lipid fluidisation
Bypass / removal
Powered electrical devices
What happens when a drug is at its highest thermodynamic activity?
It has maximum skin penetration
What happens when water is taken up from the skin into the vehicle?
If water is taken up from the skin into the vehicle and acts as a an anti-solvent, thermodynamic activity of the permeant increases drug flux by 5-10X
What is a eutectic mixture?
2 components at a certain ratio inhibit crystalline process of each other so that the melting point is less than it would be alone
What is the benefit of having a lower melting point?
The greater the solubility in a given organic solvent
Define enhancement ratio (equation)
Drug permeability coefficient after enhancer treatment / drug permeability coefficient before enhancer
How can permeation be increased through modification of the stratum corneum?
- Disruption og intercellular lipid lamellar structure
- Interaction with intracellular proteins of the stratum corneum
- Improvement of partitioning of a drug, with co-enhancer or co-solvent penetrating stratum corneum.
How does hydration of stratum corneum improve permeation?
Alters drug solubility and partitioning. It increases skin hydration, swelling and opening the stratum corneum which leads to increased penetration
How do liposomes improve permeation in the stratum corneum?
They hydrate/alter lipid layers
Deformable liposomes have solvent or surfactants to improve stability allowing them to squeeze through channels
How does keratin and lipid disruption improve permeation?
The stratum corneum is disordered
Done by:
- mixing homogeneously with lipids, changing solubility
- extracting lipids forming aqueous channels or forming microcavities within the lipid
What is the effect of shifting the solubility parameter on permeation?
Shifting the solubility parameter of the skin closer to the drug increases solubility and so increases drug permeation.
