Solid Nanoparticles (G5)

Question 1

What are the 3 methods used for the production of solid lipid nano/micro particles

Answer 1

1) O/W melt dispersion
2) W/O/W double emulsion
3) Solvent Evaporation

Question 2

What are the advantages of solid lipid nano/micro particles for controlled drug delivery? (4)

Answer 2

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

Question 3

Describe how solid lipid microparticles are produced by O/W melt dispersion

Answer 3

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

Question 4

How can the OW melt dispersion technique be improved to produce more uniform sized microspheres?

Answer 4

• 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

Question 5

Describe the process of W/O/W double emulsion to produce solid lipid nano-particles

Answer 5

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.

Question 6

Describe what is going on in this diagram

Answer 6

• 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

Question 7

What are CPT 11 crystals?

Answer 7

A chemotherapeutic agent used in cancer treatments

Question 8

Explain the process in which CPT 11 crystals are put into solid particles

Answer 8

• 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

Question 9

What are the mechanisms by which CPT 11 crystals get out of their solid lipid nano-particles?

Answer 9

1) Diffusion through the oil phase
2) Leak out due to bursting of the phaser interface

Question 10

What does this graph tell us?

Answer 10

• 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

Question 11

Describe the Solvent evaporation technique that is used to produce solid lipid nanoparticles

Answer 11

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

Question 12

How does solvent evaporation technique differ from O/W melt dispersion technique?

Answer 12

• 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

Question 13

Describe fully what this diagram shows us

Answer 13

• 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)

Question 14

After solvent evaporation, we are left with lipophilic drugs in a lipid matrix, how do these drugs get out?

Answer 14

Mostly by matrix erosion and diffusion

Question 15

What is homogenisation

Answer 15

• An industrial process used to reduce particle size and achieve a more uniform and stable dispersion of 2 phases

Question 16

Describe high pressure homogenisation

Answer 16

Employing high pressure pumps (homogenisers) to reduce particle size to a more stable and uniform distribution

Question 17

What are these?

Answer 17

Nozzles used in high pressure homogenisation

Question 18

Explain hot homogenisation

Answer 18

• 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

Question 19

Explain Cold homogenisation

Answer 19

• 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

Question 20

Describe membrane homogenisation

Answer 20

• 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

Question 21

Describe how solid lipid particles are made using spray congealing technique

Answer 21

• 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

Question 22

Describe how solid lipid particles are made using spray drying technique

Answer 22

• 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

Question 23

What are the differences between spray drying and spray congealing

Answer 23

• 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