Non-Sterile Compounding(NAPLEX)

What is Compounding?

process of combining or altering ingredients to create a medication

• FDA does not verify the safety, effectiveness, or quality of compounded drugs before they are marketed. 

They also are not commercially available

Who sets the standards for compounding?

The USP sets the minimum acceptable standards for compounding: 

• USP 795-Non Sterile compounding 

• USP 797-Sterile Compounding 

• USP 800- Hazardous Drugs 

What formulations are considered non-sterile?

oral, via tube, rectally, vaginally, topically, nasally, or via the ear

What is non-sterile compounding used for?

• Prepare a dose or formulation that is not used commercially available

• Avoid an excipient

• Add a flavor

Space requirements for non sterile compounding

Can be performed in room air but must be separated from the dispensing area and specifically designated

All containers, ingredients, and equippment must be stored off the floor
daily/continuous temperature monitoring

easy access to a sink and purified water for rising equipment and utensils

Compounding personnel requirements for non sterile compounding

there must be a specific person( or people) resonsible for overseeing the performace of the staff and the facility

staff must have proper training, with documentation with demonstrated proficency completed initally and every 12 months for non sterile compounding

What can a compounder not wear

must remove jewelry, hats, and headphones, and must notify the designated person if there is a concern for contamination

Hand Hygiene requirements for non sterile compounding?

performing hand washing with soap and water for at least 30 seconds and wear gloves

Equipment Maintenance

must be calibrated to confirm accuracy

and all measurements should be done in the metric system

do not use a metal spatula with a compound containing a metal ion

What are the two types of balances used

Class III torsion balance(Class A balance)

• has a minimal weighable quantity and a sensitivity requirement

top loading electric balance ( analytical balance or scale)

• zero'd out before weighing the product and have higher sensitivity

Minimium weighable quantity

the smallest amount that can be wieghed with an acceptable error rate

MWQ= (Sensitivity Requirement)/ acceptable error rate

Note: typical acceptable error rate is 0.05

What is there to know about Graduates?

Graduates: a type of equipment with lines on the glass that are used to measure volume

• graduated cylinders are the most accurate due to consistent diameter from top to the bottom

• the wider a graduate is, the lower the accuracy

the measurement of a graduated cyclinder is read at the bottom of the meniscus (at the center)

Measuring volumes that are < 20% of the graduated cylinders capacity can cause a measure error.

Why are syringes beneficial

accurate for measuring small volumes and thick( viscous) liquids

Two types of pipettes

volumetric pipettes (draws up a set volume)

mohr pippette graduated and can draw up different volumes

What are glass mortars used for

liquids and for mixing compounds that are oily or can stain

What are wedgewood mortars used for?

grinding dry crystals and powders(this is b/c they have rough surface)

What are porcelain mortars used for?

blending powders and pulverizing gummy consistenciesthis is b/c they have smooth surface)

What are spatulas used for?

mix & transfer ingredients from one place to another, or to flatten and grind down ingredients

what is a powder sieve

shorts powder after grinding to be a uniform size

What are types of electric mixing equipment

ointment mills, homogenizers, and grinders

What is an ointment mill?

Draws the ointment between rollers that grind and homogenize the ingredients

What is a homogenizer?

electric mortar and pestle (can be used to mix ointments creams or other semi solid preps similar to a blenders but more powerful

What is a grinder?

similar to a coffee bean grinder, used to grind hard tablets into a rough powder that will need further manipulation to make a fine powder

What are ointment slabs

Ointment slabs are hard and non-absorbable surfaces used for mixing ointments and cream

can also be used to form pills( aka a pill tile)

Disposable parchment ointment paper can be used if the water content is not too high

When should a water bath be used on a hot plate

useful when the temp needs to be carefully controlled

What is the benefit of a magnetic stirrer

continuously stirs ingredients through a stirr bar being placed in the glass and the hot plate has a rotating mangetic plate under it cauing the stir bar to rotate

What is a tablet press?

Two plastic or metal plates used to compress powder into tablets

Compounding ingredients

contain an active pharmaceutical ingredient and excipients

If there is an ingredient without an expiration date, the pharmacist will assign a expiration date no more than what____?

3 years from the date the pharmacy received them

What is a surfactant?

Lowers the surface tension between 2 ingredients in a preparation to make more miscible (easier to mix together)

- considered amphiphilic(hydrophillic on one side and hydrophobic on the other)

Example of surfactants

• Span
• Tween
• PEG
• Poloxamer
• Sodium lauryl sulfate

What are wetting agents/levigating agents?

a surface-active substance that reduces the surface tension of a liquid to promote wetting or adhesion of a solid and a liquid

What are examples of wetting agents?

• Lipophilic: Mineral oil

• Hydrophilic: glycerin or propylene glycol

What are suspending agents?

Keep solid particles from settling in a liquid

Does not work for long and they will have to be reshaken also called dispensants

Examples of suspending agents?

Ora-plus, Ora-Sweet

What is simethicone an example of?

Anti-foaming agent

What are Glycols and gels?

- Used as surfactant & delivery vehicles
- Have wide applicability due to having hydrophilic & hydrophobic parts

What are emulsifiers

type of surfactant added to emulsion in order to keep the liquid drops dispersed throughout the liquid vechile

What is a binder in compounding?

Binder allows the contents of a tablet to stick together while perminting the contents to be released once ingested

Provide strength and stability

Examples of a binder

Acacia

starch paste

sucrose syrup

compressable sugar

Examples of diluents

Tablets: Lactose, Starches, Calcium salts, Cellulose, Petrolatum

Liquid: water, glycerin, alcohol

Topical diluents and fillers: petrolatum, mineral oil and lanolin

What is a disintergrant

Facillitate the breakup of a tablet after oral admin because oral products have to be dissolved to be absorbed can swell by absorbing water

Examples of Disintergrants

Alginic Acid

Cellulose products

Starches

What is an example of lubricant?

Magnesium stearate

What is a preservative

sows or prevent growth of micro organisms required in most preps except if sterile and immediate use

Do not use preservitives in neonates

What are some examples of preservatives?

• Chlorhexidine
• Povidone-iodine
• Sodium benzoate/benzoic acid, benzalkonium chloride
• Soric acid/K sorbate
• Methyl/ethyl/propyl parabens
• EDTA
• Thimerosal
• Catylpyridinium Cl

Buffers for acidic pH

hydrochloric acid
acetic acid/sodium acetate
citric acid/sodium citrate

Buffers for alkaline pH

Sodium hydroxide
boric acid/sodium borate
sodium bicarbonate/sodium carbonate

buffers for neutral pH

sodium biphosphate/ sodium phosphate
potassium phophate/ meta phosphate

What is an adsorbent?

keeps powders dry and prevents hydrolysis reactions

What is magnesium oxide/carbonate and kaolin an example of?

Adsorbants

Coatings

prevent degradation due to oxygen, light, moisture, mask unpalatable taste
enteric coating prevent drug degradation in the stomach for drugs that can be destroyed by stomach acid

What are examples of coatings?

Shellac, gelatin, gluten

Cellulose

Gelling (thickening) agent, stabilizer

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

cellulose and bentonite commonly used

What are humectants?

Substances that absorb moisture or promote the retention of moisture. to prevent compounds from becoming dry and brittle

What are examples of Humectants?

glycerin or glycerol, proplyene glycol, PEG, lecithin

Glycols as solvents

have low freezing point high boiling point and are water soluble

PEG has a low toxicity and low systemic absorbtion used as a surfactant, solvent , lubricant, and is water soluble and miscible

when PEG is linked to a protein drug it increased the half life

What is an emollient?

• Moisturizer/cream that soften and smooths skin
• Humectants are put into many emollient formulations to pull water in from the atmosphere to moisturize skin

• Water content: ointments (least amount) < creams < lotions(most amount)

What are the 4 examples of ointments?

• Petrolatum
• Aquaphor
• Polybase
• Aquabase
"PAPA"

What ointment is an example of oleaginous (no water)?

Vaseline

Suppository bases must be

Must be hard enough to be briefly handled, but soft enough to melt easily once inserted.

Examples of Suppository bases?

Polybase

Vegetable oils

PEG

Gelatin

When should alcohol be avoided in compounding?

Children

When should Aspartame be avoided in compounding?

PKU

When should gelatin be avoided in compounding?

vegetarians, vegans, or a patient who wants to avoid animal products

When should Gluten be avoided in compounding?

Celiac Disease

When should lactose be avoided in compounding?

lactose intolerant

When should preservatives be avoided in compounding?

neonates

When should sugar alcohols be avoided in compounding?

IBS

When should sucrose be avoided in compounding?

Diabetes

When should Xylitol be avoided in compounding?

Dogs

What data sheet is required for each bulk ingredient?

SDS (safety data sheet): helps to determine safety procedure and recommended PPE

What excipients do powders include

Glidants/ lubricants to improve the flowability(mag sterate)and surfactants to neutralize the static charge(sodium lauryl sulfate)

What is comminution?

This is the overarching term for reducing the particle size of a solid substance to make it finer.

Methods

• Tituration

• Pulverization

• levigation

What is trituration?

grinding, crushing, or rubbing a powder or crystal into a fine particle size using a mortar and pestle.

What is levigation? What is spatulation?

Levigation involves triturating the powder with a mortar and pestle by incorporating a small amount of *liquid*, AKA a *levigating or wetting agent*, to help with the grinding process. Levigation will turn the solid into a uniform paste.

Spatulation is similar to levigation, but performed on an ointment slab with a spatula (instead of a mortar and pestle).

What is pulverization?

used for crystalline powders that will not crush easily; crystals are dissolved with an intervening solvent and mixed until the solvent evaporates

- when powder recrystallizes, the particles are finer

What is geometric dilution?

Method of mixing ingredients to ensure ingredients are evenly distributed in a diluent or delivery vehicle
• Small amount of the drug is mixed into an equal amount of the diluent

If melting ingredients, melt the ingredients with the

highest melting point before adding ingredients with lower melting points

What is an eutectic mixture?

• The combination of ingredients melts at a lower temp than either of the individual components melting temp

What is a SOLUTION?

• Solute dissolved in a solvent
• Homogenous (uniform throughout)

What are the different types of solutions

• Syrups: A drug dissolved in a solution of sugar, water and sometimes a flavoring to disguise an unpleasant taste.
• Elixirs: Clear, sweetened, hydro-alcoholic mixture used for drugs insoluble in purely aqueous mixture
• Tinctures: plant or animal extracts dissolved in alcohol or hydroalcohol
• Spirits: alcohols or hydroalcohols of voltiale , aromatic compounds such as camphor

"SETS"

What is a SUSPENSION?

solid dispersed in a liquid. it is 2 phase heterogenous mixture

a wetting agent/levigating agent used to incorporate and insoluble drug in a liquid

What is an EMULSION?

a liquid dispersed in a liquid

two phase heterogenous wit there. being oil in water ( oil in an aqeous vehicle) or water in oil

emulsifier is used to keep the liquids from separating

What is PRECIPITATION/SEDIMENTATION?

• Dispersed phase settles (clumps) together

How to prepare suspension?

• Gather ingredients
• Reduce particle size into fine powder
• Wet powder and levigate to form paste
• Add surfactant to keep suspension dispersed

- Will need to be redispersed (shaken) before use

An emulsion is parts oil + _ parts water + __ parts gum

4 + 2 + 1

Steps to prepare emulsion with continental gum method (dry gum)

1.Levigate the gum with oil
2.Add water all at once
3.Triturate until a cracking sound is heard and the mixture looks creamy white
4.Add other ingredients & water sufficient to make the final volume
5.Homogenize the emulsion

Steps to prepare emulsion with English gum method (Wet gum)

1. triturate the gum with water to form mucilage(thick and sticky like mucus)

2. Add oil slowly

3. Add other ingredients as in the dry method

Steps for compounded molded tablets

• Measure & weight all ingredients
• Triturarte the dry ingredients
• Mix the ingredients using geometric dilution
• Add alcohol and/or water to moisten the powder mixture
• Compress the moist powder mixture into a tablet mold & allow to dry

What can capsule shells be made out of?

made from gelatin or hypromellose and are filled with powders

• soft shell capusles are mostly used for oils

• glycerol and sorbitol are used as plasticizers

What is the lozenges base for hard loz vs. soft loz?

• Hard: sucrose or syrup

• Soft: PEG

suck it hard

How to prepare ointments?

• Titurate powder well using a levigating agent
• Mix into ointment base with geometric dilution

Suppository bases oil soluble

cocoa oil (store in fridge) and hydrogenated veggie oils

suppository water soluble bases

PEG and glycerated gelatin

USP definition of stability

The extent to which a product retains, within specified limits, and throughout its period of storage and use (i.e., its shelf life), the same properties and characteristics that it possessed at the time of manufacture

Beyond-use date (BUD)

- the date or time a drug or material can no longer be use determined by the water activity (Aw)

BUD for non sterile products

• Nonpreserved aqueous (Aw ≥0.6) = 14 days fridge
• Preserved aqueous (Aw≥0.6) = 35 days
• Nonaqueous (Aw <0.6) oral liquid = 90 days
• Nonaquous (Aw <0.6) other non oral liquid dosage forms = 180 days

BUD Exceptions

Ingredient expires before BUD

Stability data determines drug stable for longer period up to 180 days

Unit-Dose Repackaging:

refers to a small package that contains one dose of a medication; NOT CONSIDERED COMPOUNDING

BUDs:
- manufacturer's expiration date from original container
OR
- 6 months from repackaging date, whichever is earlier

Keep different categories of drugs separate