Non-sterile Compounding Chapter

Compounded product

Cant be commercially made

Not FDA approved

Sterile vs Non-sterile

prepared for an individual patient based on a rx

U.S. Pharmacopeia (USP) 795

Sets the standards for nonsterile compounding preparations

Minimum acceptable standards by the FDA, state boards of pharmacy, and the Joint Commission

Compounded product

Cant be commercially made

Not FDA approved

Sterile vs Non-sterile

prepared for an individual patient based on a rx

U.S. Pharmacopeia (USP) 795

Sets the standards for nonsterile compounding preparations

Minimum acceptable standards by the FDA, state boards of pharmacy, and the Joint Commission

Compounded non-sterile preparations (CNSPs)

Orally (+ via tube)

Rectally

Vaginally

Topically

Nasally

In ear

Usually to prepare a dose/formulation that is not commercially available: solid to liquid, avoid an excipient, add a flavor

Space requirements for CNSPs (5)

Can be in ambient air (room air), but must be separated from the dispensing part of the pharmacy (specifically designated)

Ingredients, equipment, and containers must be stored off the floor

Temp should be monitored daily (continuously)

Sink with hot and cold water

Purified water, distilled water, or reverse osmosis water needed for rinsing equipment and utensils

Compounding personnel requirements for CNSPs (5)

Must be designated person responsible for site

Training with documentation (proficiency in core competencies initially and every 12 months)

Core competencies: hand hygiene, garbing, use of equipment, cleaning, mixing, documentation

Must notify designated person if concern for contamination

When entering compounding area, must use hand hygiene with soap + water >/= 30s and gloves are required

CNSPs personnel requirements for garbing

remove jewelry, hats, headphones

proper hand hygiene

gloves

Compounding equipment requirements for CNSPs (3)

3 Cs: Clean, Calibrated, Compatible

Calibrated regularly to confirm accuracy

Equipment made of material that doesn't react with ingredients (metal spatula shouldn't be used with metal ion containing drugs)

All measurements should be made in the metric system

Balances used to weigh CNSPs

Class III Torsion balance (Class A balance)

Electronic balance (analytical balance or scale)

Class III torsion balance

Is a two-pan balance that uses both internal ( 1g) weights

Have a sensitivity requirement (usually 6mg) and MWQ (usually 120mg)

Never place material directly on balance (place on weigh boat or glassine weighing paper - coated to reduce moisture penetration)

when would you use external weights with a Class III torsion balance

if weighing > 1 gram

Electronic balance (analytical balance or scale)

Most common

Higher sensitivity than torsion balance (don't have to calculate MWQ)

Place weigh boat or paper on scale and tare or zero out so only the ingredients are weighed

Never place material directly on balance (place on weigh boat or glassine weighing paper - coated to reduce moisture penetration)

Graduated cylinder

used to measure the volume of a liquid

has same diameter from top to bottom of container

more accurate than conical graduates or beakers

maintaining measurement accuracy

20% rule

measure on flat surface

read volume at eye level (bottom of meniscus)

The wider the mouth of the graduate measuring device

the lower the accuracy

Measuring volumes that are smaller than _________ of the graduates capacity can cause a measuring _____________

20%

error

Syringes

Oral and hypodermic (injection/parenteral)

Most accurate for measuring small volumes

What instrument is preferred to measure viscous liquids

Syringes

Like glycerin and mineral oil

Oral Syringe safety

Clearly label by placing a "For Oral Use Only" sticker over the syringe cap

Pipettes and droppers

thin plastic or glass tubes to measure small volumes and release liquid in drops

Volumetric pipettes

Draws up a set volume only

Mohr pipette

graduated and is used to measure different volumes

Glass mortars

for liquids (suspensions/solutions) and mixing compounds that are oily or can stain

Wedgwood mortars

have a rough surface and are preferred for grinding dry crystals and hard powders

dont want to use with dyes because can easily stain

Porcelain mortars

Smooth surface, preferred for blending powders and pulverizing gummy consistencies

Spatulas

used to mix and transfer ingredients from one place to another

flat part = flatten and grind down ingredients and to pack preparations such as ointments into containers

made of stainless steel, plastic or hard rubber

- stainless steel and disposable plastic = used commonly

steel = NOT for mixtures with metallic ions

rubber = for corrosive material

Ointment slabs

flat board made of porcelain or glass

- used as a work surface for other purposes besides making ointments since the material is hard and non-reactive

can be used to form pills (pill tile), for rolling out suppositories

disposable parchment ointment pads can be used as a work surface for working with ingredients if water content of mixture will not cause it to tear

Powder sieves

sifters to ensure uniform particle size

Types of electric mixing equipment (3)

Ointment mills

Homogenizers

Grinders

Ointment mills

Draws the ointment between rollers that grind and homogenize the ingredients (make smooth and uniform)

Homogenizers

electric mortar and pestle

mix ointments, creams, semi-solids

like a blender, can be handheld and small

Grinders

Grinding hard tablets into a rough powder

Water bath

Heating device

when temp needs to be carefully controlled (protects ingredients from overheating and burning)

melted in a container (beaker) thats placed into a larger container filled with water that is on a hot plate

Molds

Reusable or disposable

To prepare tablets, lozenges, troches, suppositories

soft delivery vehicles (suppositories, lozenges) usually in a disposable plastic mold + refrigeration also helps maintain shape

tablet press

Two plastic or metal plates used to compress powder into tablets

Capsule shells made of gelatin

pork-derived

Capsules made from hypromellose

plant-derived

Ingredient quality of CNSPs (2)

Listed in USP National Formulary (USP-NF) and come from FDA-registered facility

If receive a product with a missing expiration date (needed to make sure product retains potency + is non-toxic): rph will assign a conservative date that is no more than 3y from the date of receipt

Common excipients

surfactants

binders

diluents/fillers

disintegrants

flavoring/coloring agents

lubricants

preservatives

buffers

adsorbents

anti-foaming agents

coatings (regular)

gelling (thickening) agents

humectants

surfactants

contraction of the words surface active agent

lower the surface tension bw 2 ingredients (or phases) in a preparation to make them more miscible (easier to mix) - keeps the phases from quickly separating

amphiphilic (hydrophilic on one side and lipophilic on other)

leads to delivery of a more consistent dose by keeping drug dispersed longer

surfactant examples

Benzalkonium chloride

Nonoxynol 10

Octoxynol 9

Polysorbate 80

Sodium lauryl sulfate

Sorbitan monopalmitate

Span

Tween

PEG 400

Wetting/Levigating agents

Type of surfactant

reduce surface tension bw liquid and solid

levigation

technique to grind particles (make them smaller)

mineral oil

levigating agent for lipophilic (oil-soluble) compounds

surfactant

Glycerin or propylene glycol

levigating agent for aqueous (water-soluble) compounds

surfactant

suspending agents

Suspension is a solid dispersed in a liquid

Suspending agents are added to keep solid particles from settling

Don't keep suspensions separated for long and need to be shaken to redisperse the solid prior to use

aka dispersants or plasticizers

type of surfactant

commercially available suspending agents

Ora-Plus: keeps drug particles suspended and prevents settling, slightly acidic, bland taste

Ora-Sweet: like simple syrup, provides flavor to Ora-Plus

Ora-Blend: combo of ora-plus + ora-sweet

foaming agents

mostly used in manufacturing detergents and soaps

foam reduces the surface tension bw dirt (lipophilic) and water

type of surfactant

Polyethylene glycol (PEG) and poloxamer

P in PLO gel

both are delivery vehicles and surfactants

both have hydrophilic and hydrophobic parts

type of surfactant

emulsifiers

Emulsion is a mix of 2 or more liquids that are immiscible

Emulsifiers added to an emulsion to keep the liquid droplets dispersed throughout the liquid vehicle

Hydrophilic-lipophilic balance (HLB)

Twenty-point scale (0-20, 10 is the midpoint) indicating the affinity of an emulsifying agent for oil versus water

used to select the surfactant needed to make an emulsion

Low HLB number

<10 and are more lipid-soluble

Low HLB makes it Like Lipids

what type of mixtures needs a low HLB number emulsifying agent

water in oil (w/o) emulsions - usually topical

High HLB number

>10 and are more water soluble

High HLD makes it Hug H20

what type of mixtures needs a high HLB number emulsifying agent

oil-in-water emulsions (o/w)

binders (excipients)

let tablet stick together while permitting release while ingested

provide stability and strength

ex. starch paste

diluents + fillers (excipients)

to dilute or to bulk up amount

Tablet/capsule diluents/fillers

Sugars: lactose, mannitol, sorbitol

Starches

Calcium salts

Cellulose powder

Liquids diluents/fillers

water

glycerin

alcohol

Topicals diluents/fillers

petrolatum

mineral oil

lanolin

Disintegrants (excipient)

facilitate breakup of tablet after oral admin - need to be dissolved to be absorbed

cause it to absorb water which makes the tablet swell and release its contents

ex. alginic acid, cellulose products, starches

Salty or sweet flavoring mask what flavor

bitter

Mint and spices mask what flavor

poor

Acids (citric acid) enhance what flavors

fruits

Examples of sweeteners (excipients)

Non-caloric/artificial: aspartame, saccharin, sucralose

Glycerin

Dextrose

Sugar alcohols (mannitol, sorbitol, xylitol)

Stevia

Lubricants/glidants (excipients)

Keep ingredients from sticking

-CA & MG STEARATE

-peg

-mineral oil

-stearic acid

-talc

Glidants: improve powder flowability by reducing interparticle friction

Preservatives (excipients)

slow/prevent microorganism growth

required unless sterile or packaged as single-use

usually alcohols + acids

What population would you not use preservatives in

neonates

Examples of preservatives (excipients)

Chlorhexidine (also an antiseptic in surgical scrubs)

Povidone iodine

Sodium benzoate/benzoic acid/benzalkonium chloride

Sorbic acid/potassium sorbate

Methyl/ethyl/propyl parabens

EDTA

Thimerosal (contains mercury, used in some vaccines)

Cetylpyridinium chloride

Buffers (excipients)

Keep pH in a certain range (improves stability and solubility, decreases irritation)

Buffers used to maintain an acidic pH

HCl

Acetic acid/sodium acetate

Citric acid/sodium citrate

Buffers used to maintain an alkaline pH

Sodium hydroxide

Boric acid/sodium borate

Sodium bicarbonate/sodium carbonate

Buffers used to maintain a neutral pH

sodium biphosphate/sodium phosphate

potassium phosphate/metaphosphate

Adsorbents (excipients)

Keep powders dry and prevent hydrolysis reactions

Magnesium oxide/carbonate

Kaolin

Anti-foaming agents (excipients)

breaks up and inhibits the formation of foam

simethicone

Coatings (regular) - excipients

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

enteric coatings prevent drug degradation in the stomach for drugs that can be destroyed by stomach acid

Shellac, gelatin, gluten (food grade)

Cellulose acetate phosphate

Gelling/thickening agents (excipients)

Increase the viscosity of a substance - can stabilize it

Gelatin, cellulose, bentonite common - they swell when mixed with water

Examples of gelling agents

agar

alginates

various gums (guar, xanthan, acacia)

gelatins

bentonite (clay)

cellulose

starches

poloxamer (pluronic) gels

Humectants (excipients)

prevent mix from becoming dry and brittle bc when put into emollients, humectants draw water into the skin to moisturize

Ex. glycerin, glycerol, propylene glycol, PEG

Hydrophilic Solvents

Water

Sterile water

Alcohols (benzyl alcohol, IPA 70%)

Glycols (PEG 400, polybase)

Types of water purification

Purified water has been treated to remove chemicals and contaminants: methods

Distillation

Deionization

Reverse osmosis

Carbon filtration

Distilled water

used for reconstitution to prepare oral suspensions and nonsterile compounding preparations

Potable water

Drinking/tap water

safe to drink

used for hand washing

Sterile water for injection (SWFI)

Hydrophilic solvent

used to make sterile drugs

must be free of bacterial endotoxins (pyrogens) produced by microorganisms that inhabit water

Alcohols

Hydrophilic solvents: alcohols that have high miscibility with water and can be used to dissolve solutes that would be insoluble in water

Benzyl alcohol + IPA 70%

Benzyl alcohol

used as solvent, preservative, and for aroma (fragrance)

IPA 70%

preferred disinfectant in sterile compounding

Glycols

Hydrophilic solvents: low freezing point, high boiling point, water soluble

PEG, Glycerin, propylene glycol

polyethylene glycol (PEG)

Used as a surfactant, solvent, lubricant

water soluble and water miscible

when PEG is linked to a protein drug

Pegylated - such as PEG-filgastrim, naloxegol

It increases the half life

PEG numbering

based on MW

PEG 400 used in compounding and PEG 3350 used as a laxative

Polybase

PEG mixture used as suppository base, good emulsifier

Hydrophobic solvents

oils and fats

Baby oil main ingredient

mineral oil

emollient

softens + soothes the skin (moisturizers)

humectants commonly added to pull in water from atmosphere + can be sticky

Ointments

Creams

Lotions

Gels

Pastes

Suppository bases

Best type of emollient for extremely dry or thick skin

ointment

Best emollient for normal and dry skin

cream

Best emollient for oily skin

lotions since they have the most water

Occlusive ointments

form protective barrier to prevent loss of water

petroleum jelly

theobroma oil (cocoa butter)

waxes

Definition of ointment

semisolids with 0-20% water

Ointment examples

petrolatum, polybase, aquaphor, aquabase