Lipid emulsions/parenteral nutrition (Cheng) Flashcards by Sarah Ramsbottom

What is a parenteral lipid emulsion made from?

oil in water system

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size of droplets in aliquid emulsion

90% < 1 micro m

typically 0.2 - 0.6 micro m

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Are liquid emulsions stable?

thermodynamically unstable

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shelf life of lipid emulsions

18-24 months at room temperature

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2 phases in a parenteral lipid emulsion

aqueous phase - WFI (water for injection)

2. triglycerides (oily phase)

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triglyceride component of a lipid emulsion

oil core
source of FAs
long chain TGs, medium chain TGs
mixture of LCTG and MCTG
structured lipids

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How are structured lipids made?

esterification os MCFA (medium chain) and LCFA to form mixed TGs by heat

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examples of emilsifiers for lipid emulsions

phospholipid from egg or soya lecithin

lipoid E100
Ovothin 200

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structure of emulsifiers

acyl chains typically C16-C18
phospholipid head group
charged stabilisation
ionisation behaviour

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What type of molecules ar phospholipids?

amphiphilic

- can interact with lipid and aqueous surroundings

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When does phase transitional temperature increase?

with increasing FA chain length

> van der Waals stronger
> need more energy to disrupt the packing

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How does putting a double bond in the chain affect the phase transitional temperature?

requires a much lower temperature to induce order packing rearrangement
-> lowers transitional temperature

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What does the transitional temp affect?

product stability
how lipid emulsions can be produced

-> high transitional temp - hard to filter and high melting temperature

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How parenteral lipid emulsions are manufactured?

oil phase mixed with high shear mixer in aqueous phase
creates a coarse emulsion
microfluidisation using high P pump
cooled in ice bath
fine emulsion created
coarse filtration (5 micro m)
heat sterilisaion

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What variables affect properties of lipid emulsion?

process parameters
- temeraute
- pressure
- homogeniser passes
formulation considerations
- oil conc
- emulsifier conc
- salt/electrolyte conc
- pH
- drug conc/properties

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How does temperature affect droplet size?

inc temp - reduces viscosity

-> smaller droplet size

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How does oil conc affect properties of lipid emulsion?

increased oil concentration gives larger droplet sizes

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How does emulsifier concentration affect lipid emulsions?

more emulsifier gives narrow size distribution

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How can salt conc affact lipid emulsions?

affects size distribution

affects electrostatic repulsive effects of phospholipids

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How does pH affact lipid emulsion?

increased pH gives better physical stability to the emulsion

-> because phospholipids can be hydrolysed at lower pH

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What is parenteral nutrition?

supply of nutrients bypassing the digestive tract
- non-functioning GIT

(can’t take food orally)

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What is enteral nutrition?

nutrition given by oesophagus

```
functioning GIT
sip/tube feeding
~~~

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PPN

partial parenteral nutrition

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What is PPN (partial/peripheral parenteral nutrition)?

supplement diet for patients who take food orally

can’t digest normal food properly

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How is PPN given?

peripheral intravenous catheter

2 types of PPN

lipid emulsion amino acid-dextrose solution

osmolarity and pH of PPN

< 900 mocmo/L pH 7.2

problems with PPN and how to reduce this

phlebitis - keep osmolarity < 900 mosmo/L - keep pH around 7.2

brand od PPN

Nutriflex Peri

TPN

total peranteral nutrition | complete parenteral nutrition

What do TPN contain?

``` proteins dextrose electrolytes minerals trace elements insulin (based on patient's need) ```

How is TPN given?

central venous catheter with infusion pump - subclavian or jugular

steps for compounding/dispensing parenteral nutrition

- review PN Rx - risk assessment - mixing - base solutions - add electrolytes/additives - label and check final product

What components have high omolarity in the solutions?

amino acis | dextrose

amino acid component of the base solution

- self buffered - standard or - special formulations (renal/hepatic impairment/hypermetabolic conditions and children)

What does the glucose part of the base solution contribute to?

osmolarity of the PN solution eg. dextrose - acidic

examples of the composition of lipid supplement in the base solution

soya bean oil medium chain TGs

mixing sequence for PN

1. mix glucose with AA 2. add electrolytes 3. mix lipids 4. add vitamins last

Why can precipitation occur during mixing?

due to the order of adding ingredients or because of storage (slow crystallisation)

What usually precipitates in PN solution?

calcium phosphate salts - can cause death if delivered

How to stop precipitation in PN solutions?

adjust pH to favour formation of monoobasic phosphate salt

What does the conc of free ca ions depend on?

Ca and AA sources temperature

What form of Ca phosphate salts precipitates?

dibasic phosphate salt

How to reduce likelihood of precipitation?

- adjust the mixing sequence: add phosphate first, thoroughly mix then add Ca - mix the 2 salts separately (P with AA and Ca with glucose), then combine these slowly

Will precipitated crystals redissolve?

What is the least stable ingredient of PN mixtures?

vitamins

When should vitamins be added to PN mixtures?

immediately before infusion

How are vitamins broken down?

by light and dissolved oxygen

What do vitamins interact with in PN?

packaging materials of the infusion equipment

What vitamin are most sensitive to UV light?

retinol (vit A source)

How to avoid breakdown of retinol in PN mixtures

- use overwrap - administer at night or away from daylight - use palmitate rather than acetate forms to avoid sorption loss through infucion equipment

What vitamin is the most unstable?

vitamin C - > readily reacts with O molecules - > converted to DHA via oxidation - > can convert to oxalic acid (toxic)

What are sources of oxygen that can cause oxidation of Vit C?

- dissolved air in infusion bag - aeration of infusion during material transfers - residual air in compounded bag after sealing - air transmission through bag wall (storage)

What accelerates/reduced oxidation?

accelerated by trace elements (esp copper) reduced by cysteine

What should the AA conc of PN be?

> 2.5%

What should the pH of PN be?

pH > 5

What should the dextrose conc of PN be?

> 3.3%

What shouldn't be mixed directly with lipid?

dextrose

When should lipid be added?

last when all components are mixed

What filters should be used for in line filtration of 2-in-1 and 3-in-1 formulations?

0. 2 mcm for 2-in-1 | 1. 2 mcm for 3-in-1

How often should filters be changed?

every 24hrs

What does high concs of Ca and phosphorus form?

calcium phosphate - insoluble precipitate

How to prevent precipitation?

- AA conc > 2.5% + cycteine - pH 5 - 6 - infuse solution within 24hrs of preparation - use calcium gluconate instead of calcium chloride - avoid mixing Ca and P close together during prep - total Ca+P amt < 45 mEq/L - > Ca:P 1:2