1. PARENTERALS: COMPOUNDING STERILE FORMULATIONS
CHAPTER 9
PARENTERALS: COMPOUNDING STERILE FORMULATIONS

2. CHAPTER OUTLINE Compounding Sterile Formulations LVP Solutions
Special Considerations
Regulatory Oversight
LVP Solutions
SVP Solutions
Special Solutions
Administration Devices
Laminar Flow Hoods
Biological Safety Cabinets
Clean Rooms
Aseptic Techniques in Hoods & Cabinets
Working with Vials
Working with Ampules
Syringes & Needles
Filters
Quality Assurance & Infection Control
Parenteral Incompatibilities
Units of measurement
Review

3. SPECIAL REQUIREMENTS OF STERILE FORMULATIONS
NOT a relative term
Free from bacteria and other microorganisms
No particulate material
Pyrogen–free
Stable for its intended use
Many require physiological pH
Many require osmotic pressure similar to blood

4. REGULATORY OVERSIGHT OF STERILE COMPOUNDING
Compounding is regulated by state boards of pharmacy.
USP (United States Pharmacopeia – a non-profit organization) has federal authority to set compounding and manufacturing standards.
USP chapters < 1,000 are enforceable by the FDA.
Some states accept USP standards as the state’s regulations. But some states have different regulations.

5. REGULATORY OVERSIGHT OF STERILE COMPOUNDING
Chapter <795> deals with nonsterile compounding.
Chapter <797> deals with sterile compounding.
CSP – compounded sterile preparation
The intent is to prevent harm and fatality resulting from
microbial contamination
excessive bacterial endotoxins
large errors in the strength of correct ingredients
and the presence of incorrect ingredients.

6. COMPOUNDING STERILE FORMULATIONS
Injectables
IV, IM, SC, ID
Ophthalmic
Intranasal
Otic
Inhalation

7. TYPES OF STERILE INTRAVENOUS SOLUTIONS – LVPs
Large-volume parenterals (LVPs) : > 100 ml
Correct electrolyte imbalance
Vehicle for administering other drugs
Available in plastic bags and glass bottles
Common LVP solutions:
Dextrose 5% in water
0.9% NS (sodium chloride) solution
Ringer’s solution
Lactated Ringer’s solution

8. Ports Administration port Medication port
TYPES OF STERILE INTRAVENOUS SOLUTIONS - LVPs
Ports Administration port Medication port
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9. TYPES OF STERILE INTRAVENOUS SOLUTIONS - SVPs
Small volume parenterals (SVPs): < 100 ml
primarily used for delivering medications
ampules, prefilled syringes, single or multidose vials
Additive - a drug that is added to a parenteral solution
Admixture - the resulting solution when a drug is added to a parenteral solution

10. TYPES OF STERILE INTRAVENOUS SOLUTIONS - SVPs
Ready-to-mix systems
Add-Vantage®
Add-a-Vial®
Mini-Bag Plus®
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11. TOTAL PARENTERAL NUTRITION (TPN) SOLUTIONS
Nutritional support to patients who are unable to take in adequate nutrients
Contains macro- and micronutrients
Macronutrients: dextrose and protein
Micronutrients: electrolytes, vitamins, and trace elements
Lipid emulsion: fatty acids and calories
Available in 2 or 3 liter sizes
Administered via the subclavian vein over 8-24 hours

12. DIALYSIS SOLUTIONS
Dialysis - the passage of small particles through membranes byosmosis
Peritoneal dialysis – a solution placed into and emptied from the peritoneal cavity to remove toxic substance from the body
hypertonic
administered several times a day
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13. IRRIGATION SOLUTIONS Sometimes called “splash” solutions
Container size: > 1,000 ml, designed to empty rapidly
Surgical irrigation solutions - bathe and moisten body tissue, dressing, or wash instruments
Urological irrigation solutions - maintain tissue integrity or remove blood to maintain a clear field of visi on

14. ADMINISTRATION DEVICES – ADMINISTRATIONS SETS
IV administration set
device used to deliver IV fluids to patients
have many variations.
Flow rate control
clamp on administration set
drip chamber
controller
combination controller/pump
volume control chamber

15. ADMINISTRATION DEVICES – POSITIVE PRESSURE PUMPS
Cassette pump
for ambulatory patients
Syringe pump
very useful in neonatal, infant, and critical care applications
Peristaltic pump
micro-pulses
uses tubing that is reinforced with silastic insert
Elastomeric pump
balloon-like reservoir

16. ADMINISTRATION DEVICES – PIGGYBACKS, HEPARIN LOCKS
A piggyback is a SVP admixture that is administered through an existing IV line.
Usually over a short time, from 30 minutes to 1 hour
Heparin Locks
Used if no primary LVP is available
Heparin is used to fill tubing, preventing blood clots.
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17. LAMINAR FLOW HOODS (LFH)
Enclosed work area designed to establish and maintain an ultraclean work area
Air is pushed through a high efficiency particulate air (HEPA) filter that removes 99.97% of particles > 0.3 µm.
Air flows over work surface at a uniform velocity (i.e., laminar flow) of ft./min.
USP Chapter <797> requires LFH to be ISO Class 5 environments.
no more than 3,520 particles ≥ 0.5 µm
Both horizontal and vertical designs

18. LAMINAR FLOW HOODS (LFH) – HORIZONTAL HOOD
HEPA filter
air out
laminar flow viewed from above
intake filter
Hoods should run at least 30 minutes before use
Explain air flow
air in
blower
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19. LAMINAR FLOW HOODS (LFH) – VERTICAL HOODS
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20. BIOLOGICAL SAFETY CABINETS
Designed differently than laminar flow hoods
Protects personnel and the environment
Class II, Type A1 cabinets are recommended for preparing chemotherapy agents.

21. CLEAN ROOMS
Sterile compounding must be housed in an area isolated from the main traffic – a clean room.
Need an ISO Class 7 environment
no more than 352,000 particles ≥ 0.5 µm per cubic meter of air
have unrestricted air flow
only designated personnel in space
If the clean room is ISO Class 5 environment, LFH/biological safety cabinets are not required.

22. ASEPTIC TECHNIQUES
Sum total of methods and manipulations required to minimize the contamination of CSPs
Can’t say this loudly enough: Working in a LHF or biological safety cabinet does not, by itself, guarantee the sterility of CSPs. ASEPTIC TECHNIQUES MUST ALSO BE USED.
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23. PREPARING LHF (AND BIOLOGICAL SAFETY CABINETS)
Turn the hood “on” at least 30 minutes before use.
Maintain a designated clean area around the hood.
Thoroughly clean the hood.
Use the correct cleaning order for the interior surfaces of the hood.

24. ASEPTIC TECHNIQUE – COLLECT SUPPLIES
Gather all the necessary materials for the operation and make sure they are
not expired
free from particulate matter such as dust
and have no leaks -- check by squeezing plastic solution containers
Only essential objects and materials necessary for the product preparation should be placed in the LFH.

25. ASEPTIC TECHNIQUE – GROWING AND HAND WASHING
All jewelry should be removed from the hands and wrists.
Put on lint-free garments and barrier clothing.
Note: there is a proper sequence for dressing.
Wash hands and forearms thoroughly.
use antibacterial soap
work soap under fingernails
interlace fingers
wash up to elbows
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26. ASEPTIC TECHNIQUE – WORKING IN A LFH
Work without interruptions.
Place nonsterile objects downstream from sterile objects inside the LFH.
Place larger objects toward the front of the LFH away from the HEPA filter.
Do not eat, drink, talk, or cough in the LFH.

27. ASEPTIC TECHNIQUE – WORKING IN A LFH
Plan a work area at least 3 inches from the back and 6 inches from the front of the LFH.
Make sure nothing obstructs the flow of air from the HEPA filter over the work area.
Nothing should pass behind a sterile object and the HEPA filter in a horizontal airflow hood or above a sterile object in a vertical airflow hood.
Swab with an alcohol wipe all surfaces that require puncture. Use a new wipe with each surface. 27

28. WORKING WITH VIALS Two types of vials used to make admixtures
for drugs already in a solution
for drugs in a lyophilized powder that must be dissolved in a dilute to make a solution.
To withdraw a solution from a vial
Introduce a volume of air into the vial equal to the volume of solution to be removed .
Draw the solution into a syringe and remove air bubbles.
Remember that the plunger and the tip of the syringe are sterile and must not be touched.

29. CORING
Coring is when a needle damages the rubber closure of a parenteral container causing fragments of the closure to fall into the container and contaminate its contents.
To prevent coring
Place the vial on a flat surface and position the needle point on the surface of the closure at about a 45° angle.
Put downward pressure on the needle while gradually bringing the needle to an upright position (90° angle).
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30. AMPULES An ampule is a single-dose-only drug container.
Gently tap the top of the ampule to bring the medication to the lower portion of the ampule.
Clean the neck with an alcohol swab; then grasp the ampule between your thumb and index finger at the neck while keeping the swab still in place.
Forcefully snap the neck away from you.

31. AMPULES
To withdraw solution from an ampule, tilt the ampule to about 20° down and use a filter needle or filter straw to remove the solution.
Position the needle or straw on the shoulder area of the ampule. Place the beveled edge against the side of the ampule.

32. SYRINGES AND NEEDLES Basic parts of a syringe
barrel - tube that is open at one end and tapers into a hollow tip at the other end
plunger - piston-type rod with a slightly cone-shaped stopper that passes inside the barrel
tip - attachment point for a needle
Common types: Slip-Tip®, Luer-Lock®, and Eccentric tips®.
Available in sizes from 1 ml to 60 ml.
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33. SYRINGES AND NEEDLES Basic parts of a needle
hub – at one end of the needle; attaches to the syringe
shaft – long stem of the syringe
bevel – angled end of the syringe forming a point
Needles are made of stainless steel or aluminum.
Needle lengths range from 3/8” to > 3 inches.
Needles come in gauges ranging from 27 to 13 (higher the gauge number, the smaller the lumen size).
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34. FILTERS Two types of construction Found in many types of packaging
depth filters – twisting channels through the filter material
membrane filters – small pores of a uniform size in filter material
Found in many types of packaging
round plastic holder
flat plastic holder such as a final filter
inside a needle such as a filter needle
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35. FILTERS
Depth filter – filters a solution either pulled into or expelled out of a syringe
but not both ways with the same filter
Membrane filters – filters only a solution expelled out of a syringe

36. QUALITY ASSURANCE (QA) - FACILITIES
USP Chapter <797> requires every compounding facility has to have a QA program.
Environmental Quality and Infection Control Plans
certification of ISO class
monitoring of airborne particulates and microbiologicals.
cleaning and sanitizing compounding areas.
hazardous materials regulations.

37. QUALITY ASSURANCE (QA) – COMPOUNDING OPERATIONS
Proper preparation of product
Inspection and final check of product
container integrity and leaks
product cloudiness, particulates, color
Sharps disposal
Sharps are objects that might puncture or cut the skin of anyone who handles them.
Containers should be easily identified, leak proof, puncture proof, and be able to be sealed permanently.

38. PARENTERAL INCOMPATIBILITIES
drug and drug incompatibility
drug and IV solution incompatibility
drug and parenteral container incompatibility
Characteristics of incompatibilities
color change
hazy appearance
precipitations
gas evolution
chemical degradation

39. PARENTERAL INCOMPATIBILITIES – HOW TO MINIMIZE
Use solutions promptly after preparation.
Minimize the number of drugs that are added at one time.
Check references or package inserts if additives
will result in a very high or very low solution pH
contain calcium, magnesium, or phosphate salts
contain acetate or lactate

40. PARENTERAL INCOMPATIBILITIES – CONTRIBUTING FACTORS
pH (degradation, precipitation)
Light (degradation)
Temperature (stability)
Dilution (proper concentration may avoid incompatibility)
Buffer capacity (change pH)
Time (degradation)

41. PARENTERAL INCOMPATIBILITIES – CONTRIBUTING FACTORS
Filters
Inline filters cause 90% reduction in nitroglycerin.
Solutions
Amphotericin B is not compatible in NS.
Chemical Complexation
Calcium reduces tetracycline activity.
Needles or filters containing aluminum should not be used with Cisplatin-AQ.
Plastics
Some drugs may bind to plastics.
Plasticizers can leach out of plastics – may bind to some drugs.

42. UNITS OF MEASUREMENT Molarity
A mole is the number of grams numerically equal to the molecular weight of the drug.
Osmole
Equal to the molecular weight of the drug divided by the number of ions formed when a drug dissolves in solution.
Osmole = molecular weight
# of ions

43. UNITS OF MEASUREMENT Equivalent Percentage weight per volume (w/v)
Equal to the molecular weight of the drug divided by the valence of the ions formed when a drug dissolves in solution.
Equivalent weight = molecular weight
Percentage weight per volume (w/v)
Refers to drug’s weight per 100 ml if drug is a solid
Refers to drug’s volume per 100 ml if drug is a liquid.
Solid: % = weight (gm)
Liquid: % = volume (ml)
valence
100 ml
100 ml

44. UNITS OF MEASUREMENT International Units (IU)
Drug potency varies between biological sources.
penicillin
insulin
heparin
vitamins