Lecture 2 - formulation design Flashcards
How do we select a good candidate for a transdermal route?
The permeant should have a molecular weight between 300-500KDa, Log P between 1-3.5 and its aqueous solubility should be over 100mg/ml. These properties can provide us with a transdermal delivery of 1mg/cm2/day.
State the equation to determine flux of a permeant.
Log Kp = Log P - 0.0061MW - 2.74
List the possible formulations and their main property.
- Semisolid formulation- these are used to increase the residence time on the skin.
- Transdermal patches- these are used for extending the drug delivery through the skin
- Liquid formulations- these are used for rapid and short term drug input into the skin.
Rules for the formulation?
The drug must be stable.
Drug and excipients must be compatible
Drug must be released from the dosage form following application
The formulation should be acceptable for better compliance
Give an example of the right design of a formulation to ensure the appropriate release.
A lipophilic drug should be in an aqueous base so that the drug is more likely to partitioned following application to the lipophilic skin barrier. So the vehicle should allow some solubility of the drug but should not retain the drug by being a very good solvent.
Why consider thermodynamics for a formulation?
Flux = Concentration x Permeability coefficient
Saturated solution will deliver more of the drug. Saturated solution gives a more thermodynamic activity
How to achieve supersaturation?
Can use volatile vehicles or an anti-solvent. A drug in a poor solvent reaches supersaturation at a lower concentration. use unstable formulation but should use polymers to prevent crystallisation.
How do occlusion helps drug delivery?
It helps by letting the stratum corneum to equilibrate with the underlying epidermis. This also promotes delivery of hydrophilic and hydrophobic compounds.
What do enhancers do?
They are chemical that interacts reversibly with the skin to promote drug flux. They typically disrupt the lipid structure found in the stratum corneum. Can also alter the intracellular keratin conformation and can form a reservoir. Examples of enhancers are azone, dimethylsulphoxide, dimethylformamide, dimethylacetamide. The most commonly used chemical such as SLS, propylene glycol and urea have some enhancement activity.
Describe the formulation testing.
The first test is normally a release test with a Franz-type diffusion cell which uses a polymer membrane. However it does not show the effects of enhancers or vehicles on the skin.
Can also use the in vitro permeation using a human skin to measure the flux
Define bioequivalence.
It is defined as no significant difference in rate at which the drug is leaving the formulation and crossing the stratum corneum.
Name a few advanced formulations.
Heating the skin by 10 degrees double the delivery.
Ablation of the skin by lasers and radiowaves.
Drill hole in nails.
Vesicles
Iontophoresis
Microneedles.
What are liposomes and what are they used for?
They are lipid vesicles that enclose an aqueous volume. The lipid molecules form a bimolecular layer. Often made of phospholipids or cholesterol. Their diameter ranges from nm to micrometer. They can trap hydrophilic molecules in the aqueous core and lipophilic molecules within the membrane.
Give the different types of liposomes and how are they different.
- Standard liposomes - made of phospholipid with or without cholesterol.
- Niosomes -made of non-ionic surfactants
- Pegylated - increases circulation residence
- Ethosomes- high ethanol contents (30%), soft phospholipid vesicle
- Transfersome- deformable liposomes
- Novasome - Non phospholipid liposomes
How do liposomes help with skin delivery?
On bulk of skin, liposomes adsorb to the skin and fuse to the skin. This increases the thermodynamic activity of the drug causing the permeation of lipophilic drug. However it does not work for protein molecules as the skin barrier still remains. Liposomes are used to treat acne, alopecia and some cancers and for systemic delivery.
