PPC IV Exam 3

pMDIs (pressurized metered dose inhalers)

evaporation of propellant when inhaler is actuated

how do you breathe with pMDIs

slow and deep to fill lungs to capacity. hold breath prior to exhalation for more drug entry and more time for the drug to settle

what is the critical requirement for pMDIs

coordination

what do you use if a pt cannot coordinate?

Use a spacer, this helps aerosols travel a little longer. The bigger particles will not go into the lungs.

what are the dosage forms for pMDIs

solutions or suspensions

DPIs (dry powder inhalers)

drug preloaded into the device or filled into a hard capsule or foil blister which is loaded prior to use

breath pattern for DPIs

fast and deep. must breathe fast enough to cause aerosolization

disadvantage of DPIs

can cause pt to cough due to breathing in "dust"

drug loss due to impaction

dosage forms of DPIs

unit dose or multi-dose , powders in blisters or capsules

nebulizers

generates droplets of aerosols

breath pattern for nebulizers

inhaled during normal tidal breathing, no specific pattern

dosage forms of nebulizers

solutions or suspensions

when to rinse your mouth

when using corticosteroids

Determine the product: has a propellant like HFA

pMDI

Determine the product: powder form and sometimes contains lactose

DPI

Determine the product: a nebulizer machine is needed and it looks like normal suspensions or solutions

nebulizer

advantages of pMDI

no contamination risk, easy to use, compact, accurate

disadvantages of pMDI

specific techniques, dose limit, contamination risk due to spacers

advantages of DPI

no specific coordination, propellant unnecessary

disadvantages of DPI

can trigger coughing (inhaling dust)

dose depends on inhalation rate

advantages of nebulizer

used with most drug solutions

no specific inhalation

allows for larger doses

disadvantages of nebulizers

time consuming

high risk for contamination

bulky

not easily portable

role of a spacer

extension device that helps reduce inhalation/actuation coordination dependency , slows down the velocity and allows for more time for the propellant to evaporate and reduce the particle size of the aerosol

who uses spacers

patients who have difficulty coordinating using pMDIs

can also use nebulizers with pMDIs and patients who are unable to coordinate.

which inhalation product contains lactose

DPI

what is lactose used for

used as a carrier: micronized drugs are attached to the carrier and placed in a capsule or blister; when it is actuated by pressing a button, it is punctured and holes are made; when the patient inhales fast, the turbulent air will cause the detachment of drug from the carrier; only the drug will go to the lung and the lactose carrier will not

instructions for pMDI

shake, hold, exhale, inhale slowly, hold breath for 10 seconds

instructions for DPI

fast and deep breath; hold for 10 seconds. do not swallow capsules, rinse mouth after use to prevent oral thrush due to corticosteroids

advantages of pulmonary delivery

bypasses 1st pass metabolism, reduces adverse drug reactions, and manages airway diseases due to being selective towards receptors in the lungs versus receptors in the other areas of the body

fast onset of action, low drug dose needed

requires sterility and particulate matter testing, but no requirement for bacterial endotoxin testing

desired range of aerodynamic diameter of aerosols for pulmonary delivery

1-5 um

mechanism for aerosols to deposit

gravitational sedimentation for the size between 1-5um

mechanism for aerosols to lose

inertial impaction for the size > 5 um, and Brownian diffusion for the size < 1um

how can breathing patterns impact how much drug is able to reach the desired target

slow breath to reduce loss due to inertial impaction

deep breath (good for all) will allow for more air to get into the lung and thus more drug (which is dispersed in the air) will enter the lung

breath holding (good for all) will give more time for the drug to disperse in the air to settle to the surface of the lung for action either locally or systematically

loading dose is not the expected dose, dose depends on the patient and how well they breathe it in

dosage forms for IV products

aqueous solutions or o/w emulsions (water is external phase can be miscible with blood)

dosage forms for SubQ products

aqueous solutions and suspensions

dosage forms for IM products

aqueous or oily solutions & suspensions

intramuscular injection: oily suspensions & solutions

must partition first (if using oil)

if using aqueous (solutions) everything is soluble so need to mix

only IM allows for the oil to be used as a vehicle (slower, lasts longer)

suspension: drug needs to dissolve first

sterility

this is a test that is required

must be absent of viable microbes

must add preservatives for multi-dose vials

can be preservative free for single-dose

particulate matter

testing is required and must be particulate free

meet USP requirements (method: count numbers of particles)

solutions must be free from particulate matter > 10 um

check for visible particulates > 50um before use

want it to be clear

endotoxins

not zero tolerance, can have a certain quantity as long as the number does not exceed the limit (EU limit)

definition: a by-product of bacteria & very hard to move

must have dry heat and time to destroy (to eliminate)

pH for parenteral products

7.4

doesn't have to be this exactly, just within that range

tonicity: 0.9% NaCl

desired, but can be within an acceptable range

general consideration for parenteral products

the types of excipients required for nonsterile products still apply, but not all excipients in each type can be used; should check in an excipient can be used in parenteral products and what is the amount limit

specific considerations in selecting water and vehicles for dissolving drugs

sterile water for injection

*not for IV due to having no tonicity

specific considerations in selecting water and vehicles for flushing tubing

sterile water for injection

specific considerations in selecting water and vehicles for preparing dilutions for intravenous administration

sodium chloride injection: isotonic, sterile for IV (using normal saline only)

0.9% sodium chloride for injection

specific considerations in selecting water and vehicles for small volume injection or flushing

bacteriostatic water & bacteriostatic NaCl (not for use in neonates) already has preservatives

contains antimicrobial agents

do not use a larger volume for this, if you do then you will have larger preservatives, and the more/larger of your preservatives the more toxic it will be (esp. benzyl alcohol)

can you have coloring agents in parenteral products

NO GIRL

sterilization methods: steam

first choice

terminal or autoclave

heat + moisture

can't use oil (oleaginous preparations) because no water can get in

sterilization methods: dry heat

heat stable powder

for oils, fats & oleaginous preparations

for depyrogenation

destroying pyrogens that's within endotoxins

sterilization methods: ionizing radiation

doesn't generate heat

use if substance cannot tolerate heat

sterilization method: gaseous

can be toxic to operators

terminal

sterilization method: sterilization by filtration

0.22 um (for solutions only)

non-terminal

for solutions & gases

can't use emulsions or suspensions

most used in sterile compounding

commonly used containers

glass or plastic

can you have mutli-dose and single dose

YES

glass

more inert (not reactive) preferred over plastic

must be transparent

type 1 preferred for glass and doesn't cause any changes with product

most resistant to chemical deterioration

type 2 or 3 can be used with some products

plastic

less inert = more reactive

free of DEHP due to the DEHP bc it can cause contamination

can be made out of PVC. If it is, then you will have DEHP, which will leach out, contaminating the solution. When product contains cosolvent, it can cause a lot of toxicity.

can be made out of different materials, if made out of this material then it will not have DHEP

want to use latex-free products for rubber closure (due to human allergies bc rubber has latex)

SVP (small volume parenteral)

single-dose injections packaged in containers

volume is 100ml or Less

LVP (large volume parenteral)

no preservatives (bc of toxicity), single-dose injection for IV use, no bacteriostatic agents

volume > 100ml

TPN (total parenteral nutrition) & TNA (total nutrient admixture)

provides essential nutrients (carbs from dextrose, protein from AA, multivitamins from trace elements, eetc & lipid from lipid emulsion)

TNA

amino acid, dextrose, + other trace elements (lipid o/w type is included). same container

can use normal infusion (depends on osmolarity)

TPN

high concentration & high osmolarity (use central vein)

PPN (peripheral parenteral nutrition)

low concentration & low osmolarity

still hypertonic but less hypertonic than TPN, thus can use peripheral vein if there is no lipid added)

type of injectable lipid emulsions

o/w so it can dissolve in the water (water is external phase and blood is water) you want it to be miscible in blood (not dissolved)

filter needle size

5 um

sterilization filtration needle size

0.22 um

administration with TNA size

1.2 um because TNA contains the lipid emulsion

if you use 0.22 um then it wont pass through it, it will remove everything through the filter; everything will be bigger than that filter size

what factors increase the risk of precipitation of calcium phosphate TPNs

pH = lower, for soluble one, pH of final should never be higher = precipitation occurred

temp = lower

Ca2+ = lower for soluble one

AA = higher, for soluble one

what type of dosage forms are insulins

solutions or suspensions

what are the proper administration instructions for insulin products

rotate gently, do not shake

ensure its clear for solution or uniformly cloudy for suspension

do not place in a freezer or leave in heat because it can denature

rotate site of injection, if you didn't rotate then it will decrease absorption

What are the requirements for sterile compounding facilities in terms of ISO class of air and disinfection?

perform in ISO Class 5 (just remove particles, not sterilize)

disinfect everything

ensure sterility and particulate free

What is primary engineering control (PEC) critical sites, first air, & laminar airflow workbench (LAFW)?

ensure it is exposed to air, so first air can blow out parts at anytime (no blocking)

syringe (tip of needle), needle, vial and ampules, additive bags

*critical sites are the parts of supplies and bags that have greater risk of contamination, subsequently causing the contamination of CSPs, such as tip of needle, rubber closure of vial, ampule opening, and additive port of IV bag

first air = air comes from HEPA filter, air blows out particles, no blocking in the air, be aware of direction so you know how to position supplies that are critical sites

laminar airflow workbench = first air for compounding

disinfection is required: everything must be sterilized (bench, hood, glove, all supplies, even the injection site)

Is disinfection required for PEC?

disinfection is required, everything must be sterilized (bench, hood, glove, all supplies, even the injection site)

How do you classify the risk level of compounded sterile preparations (CSP)?

Classify risk levels by ingredients/admixtures (how much is added)

What CSPs are considered high risk and must be sterilized?

high risk: admixtures with nonsterile ingredients; whenever you use something nonsterile

What are the required tests for these high-risk CSPs?

sterility test, bacterial endotoxin test, particulate matter test

steps of aseptic technique

gather supplies

disinfect everything

prepare syringes (open everything and ensure critical sites are properly facing airflow)

enter vials (avoid coring - pieces of rubber come into solution if not injected properly)

withdraw from an ampule (using a filtered needle, ALWAYS, may inject glass if not)

inject into solutions (never use the same filter needle to withdraw and inject); allow the port to dry first after disinfecting (disinfect before any injection), then inject, don't puncture the bag. do not use the filter needle; filter needle is only used when withdrawing solution from an ampule

Cover & label product: main label & auxiliary label

What are the specific considerations in the following?

Required by all: no critical sites are touched, the flow of first air to critical sites must be maintained

specific considerations to enter and withdraw from a vile

rubber closure should be wiped before puncture

prevent coring (rubber pieces getting into solution and causing contamination)

withdrawing: add equal amount of air as the volume to be withdrawn to the vile

-if more air added = positive pressure and solution with spray out

-if less air added = negative pressure

specific considerations for withdrawing from an ampule

the neck should be wiped before breaking

tap the neck to move contents into the body

breakneck (not towards HEPA filter)

use a filter needle with a bevel downward and then change to a regular needle

specific considerations to add a drug solution to LVP or SVP

remove protective covering from medication port and aseptically withdraw drug

wipe medication port with alcohol 1st (rubber closure)

insert needle into port and inject additive solution

remove needle

specific considerations to reconstitute a drug powder

Sterile water for injection is preferred as a dilutent to dissolve: rotate or swirl to dissolve, not shake; check for complete dissolving

consider powder volume to know how much diluent needs to be added

vehicle is added with 2steps

wipe rubber closure first, consider coring, never shake, swirl to dissolve then check for clarity to ensure dissolution

specific considerations to thaw a frozen drug

if frozen, just thaw at room temperature or in a fridge

never use a waterbath or microwave

specific considerations to mix parenteral products

always check compatibility 1st (big concern)

mix completely after each addition of an ingredient

do not shake but rotate or swirl

specific considerations to inject parenteral preparation to a patient

site should be cleaned and disinfected

site should be rotated if frequent injections are needed

specific considerations to inspect CSPs after compounding and before administration

check particulate matter

any signs of incompatibility such as color change, precipitation, emulsion cracking

if supposed to be clear then it should be clear

preparation for lab

melt

suspend

colors/flavors PRN

pour into mold

emulsion

emulsifying agent ALWAYS

may shake

acacia emulsion (o/w)

cannot mix all together, follow order of addition

primary emulsion first then add all of the other ingredients & QS

emulsion procedure

4:2:1 ratio of oil:water:acacia

must form a primary emulsion first(key)

triturate acacia and oil in a dry ceramic mortar

measure water & add all at once with hard & fast trituration

continue until a thick white liquid is formed with a cracking sound

then gradual dilution with trituration

transfer the diluted emulsion to a cylinder

rinse & add water to the final volume

lime water emulsion

tweens and spans

just mix together

gel

must add gelling agent

Carbapol gel

challenging, must make a clear gel so you must neutralize, do not over neutralize may precipitate

gel procedure

start with water in a beaker

with magnetic stirring, sift carbapol to water

add trolamine dropwise while stirring with a glass rod to from a clear and viscous gel. measure pH, do not over neutralize (pH 6-7)

add water to the final weight as needed

ointment

no matter what base, always melt everything using a water bath (fusion method)

mixing/reaction must happen in the molten state

water phase and oil phase ointment

mix after melting,

water into oil

PEG ointment

even though 1 is a liquid, must melt them together & mix at a temperature higher than mp, allow to congeal

suppository

for perianal use

fatty base suppository

cocoa butter

key: unstable (can easily form metastable form) melting in room temp or in your hand

heat must be controlled

monitor appearance of molten liquid, should not be clear bc then it will not form a good suppository (since metastable in already formed)

water soluble base (PEG)

melt together, mix well at molten state, pour into mold if it melts at very high temperature takes longer to congeal