Compounding (copy)

Compounding USP Chapters summary

USP terminology

Air quality and HEPA filters

inside PEC (sterile hood) = iso 5

outside hood in SEC = iso 7

ante room for hand washing, etc:

- iso 8 if non-hazardous sterile + positive pressure

- iso 7 if opens up to hazardous sterile + negative pressure

Techniques to maintain sterility in PEC (hood)

What air pressure must a hazardous room have?

negative

What air pressure must a non-hazardous room have?

positive

Hazardous Drugs (NIOSH)

What temp should the SEC room be?

20 C/68F or cooler

check QD

What temp should a refrigerator be?

2 - 8°C

check BID

What temp should a freezer be?

-25 to -10°C if vaccines

- 50 to - 15 C if no vaccines

check BID

How often does air sampling need to be done?

every 6 months by a person certified in air sampling, or by a qualified compounding staff member.

How long is a media fill test incubated?

14d

Surface Sampling red flags

TAKE ACTION IF:

- > 3 CFUs in iOS 5 area

- > 5 CFUs in iOS 7 are

- > 100 in iOS 8 area

How often should air flow be checked?

QD

Hazardous drug compounding good cleaning steps

1) deactivate/decontaminate

2) clean (germicidal detergent)

3) disinfect (70% IPA)

bleach or peroxide can be used to both deactivate & decontaminate

How often should surface sampling be done in a hazardous room?

at least every 6 months to ensure that hazardous residue is adequately contained

Non-Sterile Hazardous Drugs Garbing

- Double gloves

- a gown

- a mask

- disposable pad to protect the work surface

Sterile Hazardous Drugs Garbing

- head cover

- face mask

- beard cover if applicable

- 2 shoe covers

- impermeable chemo gown

- two pairs chemo gloves (ASTM D6978)

- full face piece respirator or face shield with goggles

Sterile Compounding Garbing Steps

1) remove rings, etc

2) hair cover, face mask, show cover (2 pairs if HD)

3) wash hands

4) gown

5) gloves

Minimum weighable quantity (MWQ)

sensitivity requirement / 0.05

Mortars and Pesles

Glass : liquids

Wedgewood: crystals and hard powders

Porcelain: powders & gummy consistencies

In what case would a steel spatula not be appropriate?

not be used if making a mixture that contains metallic ions

Binders

allow the contents of a tablet to stick together while permitting the contents to be released once ingested.

They can provide stability and strength.

Diluents and Fillers

Diluents (to make something more dilute)

fillers (to bulk up a small amount)

they add size to very small dosages.

Tabs/Caps:

- lactorse

- starches

- Ca salts

- cellulose

Topicals: petrolatum

Disintegrants

Facilitates the breakup of a tablet after oral administration

Ex:

- alginic acid

- cellulose

- polacrillin K

- starges

(meds need to be dissolved when reach small intestine for absorption)

Sweeteners

Non-Caloric/artificial:

- aspartame

- sucralose

Others:

- glycerin

- dextrose

- mannitol, sorbitol, xylitol

- stevia

Lubricants

prevent ingredients from sticking to each other and to equipment

Ex: magnesium sterate

Preservatives

slow or prevent microorganism growth

Ex:

- chlorhexidine

- povidone iodine

- Sodium benzoate/benzoic acid, benzalkonium chloride

- Sorbic acid/potassium sorbate

- Methyl/ethyl/propyl parabens

- EDTA

- Thimerosal

- Cetylpyridinium chloride

**DO NOT USE IN NEONATES*

In what population can preservatives NOT be used in?

neonates

Buffers

keep the pH within a certain range, which can improve stability and solubility and decrease irritation to sensitive tissues in the body

Ionized compounds are more polar, which makes them more water-soluble.

acids maintain acidic pH

NaOH ex of buffer to maintain alkaline

Na/K phosphate ex buffer to maintain neutral

Hydrophillic solvents

- water

- sterile water

- alcohols ex: bonzyl peroxide is solvent and perservative, IPA 70% disinfects surfaces

- polyethylene glycol (when linked to a protein drug (pegylated), such as PEG-filgrastim, it increases the half-life)

Hydrophobic Solvents

Oils and fats

Ex:

- mineral oil (Baby Oil)

What is an emollient?

A fatty material used to lubricate and keep other substances on the skin

Ointments

0-20% water

Ex:

- petrolatum

- Polybase

- Aquaphor

- Aquabase

Creams

Most creams are water-in-oil or oil-in-water emulsions.

Ex:

- lipoderm

- eucerin

- cetaphil

Lotions

Lotions can be aqueous or hydroalcoholic, with a small amount of alcohol addedto solubilize ingredients, or to hasten evaporation of the solvent from the skin.

Ex: versabase

Gels

Semisolid suspensions of very small particles usually in a water base

Ex: paloxamers

- PLO gel ( liquid at fridge, gel at RT)

Suppository bases

made of various fats and glycols

have to stay intact for insertion, and melt once inserted.

Ex:

- Polybase

- hydrogenated vegetable oils (palm, coconut)

- gelatin

Adsorbents

To keep powders dry, to prevent hydrolysis reactions.

Ex:

- MgOH

- Mg Carbonate

- Keolin

Anti-Foaming agents

Breaks up and inhibits the formation of foams.

Ex: simethicone

Regular Coatings

Prevent degradation due to oxygen, light, moisture, mask unpalatable taste.

Ex:

- shellac

- gelatin

- gluten

Emulsifiers

Emulsifiers are a type of surfactant (Reduce the surface tension between two liquids to allow to mix)

Ex:

- Acacia

- PEG

Enteric-Coating

acid-resistant (enteric-coated) protective layer to prevent dissolution in the stomach.

used when drugs would be destroyed by stomach acid

(usually dissolve in stomach)

Ex: Cellulose acetate phthalate

Gelling/Thickening Agents

Increases the viscosity of a substance; can stabilize the mixture.

Ex:

- gelatin, cellulose, betonite (clay)

- Agar

- alginates

- various gums [guar, xanthan, acacia (a natural gum)]

- carbomer

- starches

- poloxamer (pluronic) gels

Humectant

Prevents preparations from becoming dry and brittle

Ex:

- glycerin

- glycerol

- propylene glycol

- PEG

Excipients to be avoided in some pts

- alcohol in children

- aspartame in PKU

- gelatin in vegetarians/vegans or pork avoider (religious)

- gluten in celiac disease

- lactose if lactose allergy/intolerance

- preservatives in neonates

- sorbitol in IBS

- sucrose in DM

- xylitol in dogs

Solutions

homogeneous mixtures : solute dissolved in a solvent

Ex:

- syrups

- elixirs

- tinctures

- spirits

Suspensions

Heterogeneous mixtures: solid dispersed in a liquid.

A wetting agent/levigating agent is a type of surfactant used to incorporate an insoluble drug into a liquid, which makes a suspension.

redispersed easily by shaking.

Emulsions

heterogeneous: liquid dispersed in a liquid oil in water or water in oil

emulsifier is a type of surfactant that is used to reduce the surface tension between two liquids (e.g., oil and water). The emulsifier allows the two phases to come closer together.

hydrophilic-lipophilic balance (HLB) number will help choose emulsifier

Precipitation/Sedimentation

when the dispersed phase settles (clumps) together. The process of a solid settling on the bottom of a container is sedimentation.

can happen with suspensions and emulsions, and less commonly with solutions. Shake or gently roll to re-disperse.

Use of Suppositories

Non-Sterile BUDs

What must be used when working with an ampule for a sterile compound?

A filter needle or filter straw will be required to remove the glass.

What must be done to vials with powder in a sterile compound?

reconstituted by adding sterile water for injection, bacteriostatic water for injection or a diluent supplied by the manufacturer.

Determining CSP Risk Level

Sterile BUDs

What is Oxidation?

loss of electrons

(when oxidation occurs, so does reduction aka gaining of electrons of the atom that took them)

What meds are at increased risk of oxidation?

Meds w/ hydroxyl OH group bonded to aromatic ring

- catecholamines: Epi, NE, DA

- phenolics: phenylephrine

How fo you precent oxidation of a compound?

- light protection (amber glass or UV-protective sleeve)

- temperature control with refrigeration

- add chelating agents to prevent run (ex: EDTA)

- add antioxidants (Vit C ascorbic acid, Vit E tocopherols)

- control pH w/ buffer

What is hydrolysis?

the chemical breakdown of a compound due to reaction with water

What compounds/meds are more likely to undergo hydrolysis?

Meds w/:

- esters: carbonyl + O-R (ASA)

- amines: carbonyl + N

- lactams: beta lactams

What can be done to prevent hydrolysis?

- light protection (amber glass or UV-protective sleeve)

- add desiccants to absorb moisture

- store as lyophilized/freeze-dried powder

- add chelating agents to prevent run (ex: EDTA)

- add hygroscopic/water-absorbing salt

- make into a prodrug that --> active agent via hydrolysis (like ASA that acetylsalicylic acid --> salicylic acid))

- control temp: occurs at higher rate at higher temp

- maintain pH w/buffer

What is the effect of hypertonic solutions on RBCs?

water moves out of RBCs (they shrink)

often given as an attempt to dilute a solute concentration in the blood, but this can cause RBCs to shriven to the point of dysfunction --> these solutions are restricted to the pharmacy

What is the effect of hypotonic solutions on RBCs?

water moves into RBCs (they swell)

this can lead to hemolysis and RBC bursting that can be fatal

What is it called when the melting point of combined ingredients is lower than them individually?

Eutectic