LIPID NANOCARRIERS Flashcards
Apply Knowledge from Lecture
Why is Ostwald ripening an issue for Nano-Emulsions? How can it be detected?
WHAT? - Ostwald ripening - small particles/droplets dissolve or deposit in larger particles forming large crystals
WHY? - Nano-emulsions are thermodynamically unstable - the difference in solubility between the smaller particles and larger particles
DETECTED? - Formation of larger oil droplets in the aqueous phase
Why is sedimentation and creaming less likely for Nano-emulsions?
WHAT? - Sedimentation (settle down) and creaming (move up) are due to phase separation/movement
WHY? - Differences in the density of the two phases. Occurs because of Brownian motion. Small particles/droplets move at random speeds.
LESS LIKELY. WHY? - Nano-emulsions don’t have two phases. Phase separation is less likely.
Explain why oil-in-water Nano-emulsions can be injected intravenously
Very small - low risk of embolism
Water is the continuous phase and has a high compatibility for blood (aqueous)
What is a ‘burst release’ and why are SLNs more susceptible to it than NLCs?
Burst Release - Rapid release of the drug into the systemic circulation. This is not ideal for Nano-emulsions because they are a modified-release formulation
SLNs are made using Hot homogenisation. Once the SLN enters the body and melts, the drug quickly escapes the oil and distributes into the water phase.
Water is very compatible with blood and leads to a rapid release of the drug into the blood.
Describe and discuss the data provided on the impact of temperature and stabiliser concentration on burst release. (Graph can be found in the lecture)
Surfactant concentration?
An increase in surfactant concentration = increases drug redistribution in the formulation.
- Decrease in friction between the oil and water phase. This allows the drug to move from the oily core into the liquid shell (water phase) - Reservoir effect
The more surfactant the faster this will occur - Rapid drug release into the circulation
Temperature?
Increase in temperature - increase in drug release by burst
Heat application - solid core is melted and liquified and allows the drug to redistribute into the water phase and out of the matrix
Temperature increases the kinetic energy of particles.
Increase the drug release from the SLN.
Compare and contrast the encapsulation models defined for SLNs. What factors will affect drug release for each model?
SOLID SOLUTION + DRUG DISPERSED WITHIN THE CORE
Oily solution - No dissolution needed. Increase in size and decrease in affinity for the core - Increases release rate
Oily suspension - the drug is dispersed in the matrix.
Slower release rate
LIPID CORE + DRUG-ENRICHED SHELL
The drug is concentrated in the periphery = Burst release.
The rate of drug release is dependent on stabiliser concentration, temperature, hot homogenisation and drug solubility
LIPID SHELL + DRUG-ENRICHED CORE
Reservoir effect
Increased concentration in the core. Controlled release of the drug.
You wish to load a weakly acidic drug into LNCs. How should you adjust the pH to maximise loading? What will be the impact on release? Justify your answer by explaining how oil: water partition will change with pH.
Weakly acidic drugs will not be ionised at a pH of 4-5 (weakly acidic)
The drug will have a higher affinity for the oil phase and will not want to leave the LNC.
This is good as it allows for more of the drug to be loaded.
Ionised - more hydrophilic - will not be happy in an oil environment.
How is the drug release of Amiodarone from an LNC impacted by solubility and drug partition?
pKa = 6.56
Weakly basic drug
@ an acidic pH, Amiodarone will become ionised.
Oil partition will decrease and the drug will become more hydrophilic.
The drug will become more soluble in water and decrease its partition from the water phase
What is the range of sizes obtained for LNCs? How can you control this parameter by changing the composition?
Limited to 100nm
More surfactant - smaller the LNC
More oil than surfactant - bigger the LNC
You have in your lab water, olive oil, Solutol ®, Tween 80 ® and paclitaxel What will be your first step in preparing an LNC
formulation?
Paclitaxel - Cancer drug
Olive oil - Lipid
Tween 80 - Surfactant
Solutol - PEG
Water - Vehicle (Continuous Phase)
Paclitaxel needs to be dissolved in the Olive oil first.
Why are medium-chain triglycerides a better solvent than vegetable oils.
MCT have a higher solubility for lipophilic substances. This makes manufacture easier.
