Solid Nanoparticles (G5) Flashcards
Goran Lecture 5 of 6
What are the 3 methods used for the production of solid lipid nano/micro particles
1) O/W melt dispersion
2) W/O/W double emulsion
3) Solvent Evaporation
What are the advantages of solid lipid nano/micro particles for controlled drug delivery? (4)
1) Solid lipid nanoparticles are more stable than O/W emulsions
2) Solid lipid nanoparticles are non-toxic because the lipids are physiologically compatible
3) They can easily be mass produced with low production costs
4) Drug solubility in hot melted oils can be high, so increased drug loading
Describe how solid lipid microparticles are produced by O/W melt dispersion
1) Dispersed phase: A lipophilic active ingredient (LAI) is dissolved in a hot melted lipid
2) This is emulsified with a hot aqueous continuous phase containing surfactant
3) This emulsion forms micro droplets of LAI lipid solution in aqueous solution
4) The emulsion is cooled (icebath) forming microspheres
How can the OW melt dispersion technique be improved to produce more uniform sized microspheres?
- After crystallisation of the melted lipid droplets into microspheres, filter the resultant microspheres
- Any microspheres that are too small or large get recycled back into the melted oil solution for emulsification again
Describe the process of W/O/W double emulsion to produce solid lipid nano-particles
Single emulsion (Water in oil):
- Hydrophilic active ingredient dissolved in aqueous solution is emulsified in a melted lipid continuous phase, outputting an emulsion of Water in oil Droplets
Double emulsion:
This emulsion is dispersed into an outer aqueous phase containing hydrophilic emulsifiers, stabilising W/O/W droplets
The double emulsion is cooled (ice bath) and hardened spheres are filtered and dried in a vacuum.
Describe what is going on in this diagram
- Hydrophilic Active ingredient in aqueous solution with a melted liquid emulsion
- This emulsion is added to an aqueous solution containing emulsion stabilisers and emulsified
- The temperature is lowered to cool and crystallise the W/O/W Droplets
- Solid lipid particles are filtered and recycled back if not to size
What are CPT 11 crystals?
A chemotherapeutic agent used in cancer treatments
Explain the process in which CPT 11 crystals are put into solid particles
- O/W melt dispersion
- Dissolve the crystals in a hot organic solvent
- Add this continuous phase to a hot aqueous solvent containing emulsifying agents
- Create an emulsion by homogenising the mixture
- Crystallise the particles by cooling, converting the droplets into solid particles
What are the mechanisms by which CPT 11 crystals get out of their solid lipid nano-particles?
1) Diffusion through the oil phase
2) Leak out due to bursting of the phaser interface
What does this graph tell us?
- Cholesterol and Compritol are both lipids used to make solid lipid nanoparticles
- how the rate of drug release depends hugely on the lipid it is dissolved in
Describe the Solvent evaporation technique that is used to produce solid lipid nanoparticles
1) Create an organic phase by dissolving a lipid in an organic solvent and adding the drug
2) Emulsify and homogenise this with an aqueous solution containing stabilisers and emulsifying agents
3) Apply pressure or heat to the emulsion, evaporating off the organic solvent, until you are left with solid lipid nanoparticles
How does solvent evaporation technique differ from O/W melt dispersion technique?
- O/W simply has a LAI dissolved in a melted liquid, while Evaporation has an organic phase, of drug, soluble lipid and lipid solvent (which is evaporated)
- No evaporation in O/W met dispersion, just cooling
Describe fully what this diagram shows us
- Solvent evaporation technique to produce lipid nanoparticles
- Start with an organic phase (soluble lipid, lipophilic drug and lipid solvent)
- Emulsify and homogenise organic phase with aqueous phase containing stabilisers and emulsifying agents
- apply heat or pressure to evaporate the lipid solvent
- With time the droplets will solidify and crystalise as the solvent is removed being left with lipophilic drug encapsulated in a lipid matrix (solid nanosphere)
After solvent evaporation, we are left with lipophilic drugs in a lipid matrix, how do these drugs get out?
Mostly by matrix erosion and diffusion
What is homogenisation
- An industrial process used to reduce particle size and achieve a more uniform and stable dispersion of 2 phases
Describe high pressure homogenisation
Employing high pressure pumps (homogenisers) to reduce particle size to a more stable and uniform distribution
What are these?
Nozzles used in high pressure homogenisation
Explain hot homogenisation
- Pre-emulsion (hot aqueous solution with surfactant mixed with a drug loaded melted lipid) is passed through a preheated homogeniser
- Fine emulsions are left to cool at room temp
Explain Cold homogenisation
- The drug disolved in melted lipid solutino is cooled and solidifies
- This solid mixture is then milled in liquid nitrogen and the particles collected
- The particles are dispersed into a cold aqueous solution containing surfactant
- The particles are then passed through a homogeniser
Describe membrane homogenisation
- A pre-emulsion solution containing lipid, API and organic solvent is prepared
- This liquid solution is pumped through a membrane that serves as a barrier only allowing the passage of particles below a certain size
- This process naturally homogenises the dispersed phase
Describe how solid lipid particles are made using spray congealing technique
- Start with a lipid melt (Drug, dissolved in a melted lipid)
- This melt is atomised (sprayed through a fine nozzle under high pressure) forming droplets that are fired into a cooling chamber
- The particles solidify upon entry of the cooling chamber and are collected
Describe how solid lipid particles are made using spray drying technique
- Start with a lipid solution (Lipid dissolved in organic solvent and drug)
- This solution is atomised (sprayed out of a fine nozzle at high pressure) forming droplets that are fired into a a heated drying chamber
- The solvent evaporates leaving solid lipid nanoparticles
What are the differences between spray drying and spray congealing
- Spray drying uses heat and a drying chamber to evaporate off solvent
- Spray drying uses a lipid, solvent and drug solution
-Spray congealing uses a cooling chamber to cool melted droplets
- Spray congealing uses drug dissolved in melted liquid
- Spray congealing recycles chilled air
