Sterile Dosage Forms- Miroshnyk

Based off of Dr. Miroshnyk's Study Guide

USP <_____> provides the minimum practice and quality standards for compounded sterile preparations.

<797>

USP <____> sets the standards for safe handling of hazardous drugs.

<800>

Injections definition:

liquid preparations that are drug substances or solutions of APIs

Injectable emulsions/suspensions definition:

liquid preparations of drug substance dissolved or dispersed or suspended in a suitable medium

If something says “for injections” is that substance a dry solid or liquid?

dry solid

Small-volume parenterals (SVP) definition:

an injection packaged in containers up to 100 ml

Large-volume parenterals (LVP) definition:

a single dose injection intended for IV use and is packaged in a container larger than 100 mL.

If I administered a 35 mL injection to a patient, would that be considered a small or large volume parenteral?

small

What are the different categories of sterile parenterals?

• parenteral injections

• ophthalmic preparations

• irrigation fluids

• dialysis solutions

• biologics

What are the advantages of parenteral injections?

• when rapid action is needed

• when pt is unconscious/uncooperative

• when pt is unable to have oral meds

• when the drug is not effective by other routes

What are the disadvantages of parenteral injections?

• must be administered by trained personnel

• the effects are difficult to reverse (overdose/hypersensitivity)

• aseptic procedure required

• contamination is possible

• invasive

• more expensive

True or False: All parenteral routes of administration are sterility-demanding.

FALSE

Is Water for Injections (WFI) sterile?

no

Water for Injections (WFI) is the vehicle of choice for…

• freely soluble APIs (injections)

• poorly water soluble APIs (suspensions)

• the external phase for injectable emulsions

Describe Sterile Water for Injection:

• package in single-dose containers

• no antimicrobials or anything else added

• pyrogen-free

• not used for IV administration

• used as a vehicle

Bacteriostatic Water for Injections is ____________ + _____________.

Sterile WFI + one or more antimicrobial agent

When using bacteriostatic Water for injections (BWFI) _______________ of the antimicrobial agents and APIs has to be considered.

compatibility

BWFI is only used for _________ volume parenterals. (small/large)

small

Examples of aqueous vehicles used for parenteral products:

• Water for Injections (WFI)

• Sterile Water for Injections

• Bacteriostatic Water for Injections (BWFI)

• Ringer’s Injection

Large volume parenterals must NOT contain what?

bacteriostatic agents or other additives

Vegetable oils are used as non-aqueous vehicles ONLY FOR _____ injection.

IM

Examples of non-aqueous vehicles for parenteral products:

• vegetable oils

  • corn, sesame, peanut, etc.

• glycerin

• polyethylene/propylene glycol

• alcohol

What are the drawbacks of non-aqueous solvents?

• pain/irritation on injection

• patients can be sensitive to the oils

Differentiate IV/IM/SQ injections in terms of onset of action.

• IV injection- fastest onset, directly introduced into bloodstream

• IM injection- in the middle- longer than IV, shorter onset than SQ

• SQ injection- slowest onset, introduced into loose interstitial tissues

What are the different methods of sterilization?

• moist-heat (steam)

• dry heat

• filtration

• gas

• ionizing radiation

Definition of Sterilization:

in pharm terms, sterilization means destruction of ALL living organisms and their spores or their complete removal from the preparation.

Describe steam sterilization:

• conducted in autoclaves

• temp is responsible for sterilization

• method of choice

Describe Dry Heat sterilization

• carried out in ovens

• higher temps and longer sterilization times

• used for sterilizing equipment (glassware, instruments, oils, etc.)

Describe filtration sterilization:

• removal of bacteria and spores by filtration using 0.22 um filter

• advantage: speed, inexpensive

• disadvantage: inspection needed, faulty assembly

Describe gas sterilization

• utilizes mixtures of ethylene oxide or propylene oxide gas w/ inert gases

• mechanism: ethylene oxide is thought to sterilize by interfering w/ metabolism of the bacterial cell

Describe ionizing radiation sterilization:

• uses gamma and cathode rays

• very reliable

• limited applications

Validation of sterility includes:

• tests to confirm the absence of microorganisms

• The USP methods

  • use biological indicators

Describe pyrogenicity tests:

• pyrogens are any fever-inducing agents like bacteria, virus, etc.

• USP injection monographs state a bacterial Endotoxin Unit Limit (USP EU)

• basically we inject bunnies and see if the drug raises the bunnies temps

List the categories of pharmaceutical excipients for parenteral products

What are the special requirements for multiple-dose containers?

MUST CONTAIN one or more preservatives no matter what

Why is the use of benzyl alcohol as an antimicrobial agent limited in parenteral injections?

• NOT FOR USE IN NEONATES!!!!!!!

• can cause Benzyl alcohol poisoning

Packaging requirements of parenterals:

• containers, including closures, must be inert

• should allow visual inspection of the solution

• should protect the product from contamination during the entire shelf-life