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Unformatted text preview: Parenteral Medications and Sterile Fluids
Sterile small- and large- volume injectable preparations (SVP, LPS), irrigation fluids
intended to bathe body wounds or surgical openings, dialysis solutions, biologicals
(vaccines, toxoids, anti-toxins) and blood replenishment products. Parenteral routes of adm inistration
1. INTRAVENOUS or I.V.
• Used in emergencies: rapid action because there is no absorption. • Optimum blood levels are achieved with accuracy and immediacy. • Useful to treat unconscious, uncooperative patients. • Drug cannot be removed once injected (if toxic effect or inadvertent overdose). • Absolute sterility requirements (aseptic handling of syringe, needles, solutions,
point of entrance). • Most expensive dosage forms. • Requires specialized personnel for administration. • Small (up to 100 ml) and large-volumes (>100 ml - 1000 ml) can be used
peripherally (e.g. veins of the antecubital area) or centrally (e.g. subclavian
vein). • Only aqueous solutions are used (exception: fat emulsion in parenteral nutrition
solutions). • Main hazards:
i. THROMBUS (thrombi, thrombosis): blood clot formed within a blood vessel
due to a slowing of the circulation or to an alteration of the blood or vessel
wall. ii. EMBOLUS (emboli): a circulating clot that can lodge in a blood vessel and
cause obstruction (pulmonary embolism, cerebral embolism, stroke). 2. INTRAMUSCULAR or I.M.
• Less rapid, greater duration than IV. • Aqueous and oleaginous solutions and suspensions may be used: variable
absorption rate. PHCY 6100- Teixeira 1 Parenteral Medications and Sterile Fluids
• Administration into the skeletal muscle, avoiding nerves and blood vessels.
Slight aspiration before injection will assure the drug won’t be injected into a
vein. In adults, the upper outer quadrant of the gluteus maximus is preferred
while in infants the best are the deltoid muscles of the upper arm or the midlateral muscles of the thigh (gluteal area is small and has very little muscle, also
close to the sciatic nerve). • Volumes administered: 5 ml if in gluteal area and 2 ml in the deltoid. • Site of injection should be rotated in a series (avoid abscess, induration) 3. SUBCUTANEOUS or Sub-Q, S.C., S.Q., Hypodermic, “Hypo”
• Administration into the loose interstitial tissue, underneath the surface of the
skin. • Small amounts: 1.3 ml max (larger amounts cause painful pressure). • Usual sites: outer surface of the upper arm, anterior surface of the thigh, and
lower portion of the abdomen. • Largely used for administration of Insulin and vaccines (MMR, DPT, rubella,
tetanus toxoid, etc). • Not suitable for irritating drugs or thick suspensions. 4. INTRADERMAL or I.D. or INTRACUTANEOUS
• Administration into the dermis (connective tissue), the more vascular layer of
the skin, just underneath the epidermis (when bevel of needle disappears into
the skin). • Usual site: anterior surface of the forearm. • Very little volumes applied (0.1 ml ) with very short and thin needles. • Used for diagnostic determinations (tuberculin, diphtheria toxin) and
immunizations (BCG vaccine). I NJECTI ONS
1. Sterility: absence of all living organisms and their spores
a) Methods of Sterilization:
i. STEAM UNDER PRESSURE (Autoclave):
Method of choice if product is thermostable. PHCY 6100- Teixeira 2 Parenteral Medications and Sterile Fluids
Higher temperatures of steam are obtained by increasing the pressure
(under atmospheric conditions steam temperature is 100_ C). It is the high
temperature that kills the microorganisms, not the pressure.
The mixture moisture + heat denatures and coagulates some of the
microbe’s essential proteins.
A standard load is autoclaved for 15 min at 121°C. In general the time
required depends on the nature of the load (dry x wet materials).
Not suited for oils, oleaginous preparations and exposed powders.
ii. DRY HEAT (Sterilizing oven):
Very high temperatures and longer periods of exposure are used (160-170°
C for 2 hr. minimum). If higher temperatures are used, shorter exposure
time can be used.
High temperature will kill microbes by dehydration of cells followed by slow
burning or oxidative processes.
Applicable to all products not penetrated by moisture such as oils, glycerin,
petroleum products (petrolatum, mineral oil, paraffin), heat-stable powders
(e.g. zinc oxide).
Also used for glassware and surgical instruments.
Microorganisms are removed by adsorption to a filter medium or by a
Bacterial filters (old fashioned) and pore-size specified filters (membranes
of cellulosic esters with pores of extremely uniform size). Membrane filters
with pore-size of 0.2 µ are considered sterilizing filters).
Useful for heat-sensitive (thermo-labile) products. Very useful for small
volumes of liquids (e.g. compounding of ophthalmics in community
Advantages: speed, low cost, complete removal of microorganisms and
Disadvantages: effectiveness of filtrate is determined by microbial load;
adsorption of certain materials to the membrane; defective filter; long time
needed if filtration of large volumes.
iv. GAS (Ethylene oxide or Propylene oxide):
These gases are extremely flammable and are used in a mixture with an
inert gas (CO 2 ).
Gas will interfere with the metabolism of the bacterial cell.
Requires specialized equipment
Longer exposure time is necessary: 4 -16 hours.
Useful for heat-sensitive and moisture-sensitive materials (enzymes,
Largely used for sterilization of medical and surgical supplies and
v. IONIZING RADIATION (Gamma rays and Cathode rays):
Rays will induce microorganisms to form deleterious products, which will
destroy the cells, and/or chromosomal nucleoproteins of microbes will
become disoriented or destroyed.
• PHCY 6100- Teixeira 3 Parenteral Medications and Sterile Fluids
• Limited use due to highly specialized equipment and unknown effects of
irradiation on products. b) Validation of Sterility: confirmation of absence of microorganisms and spores.
BIOLOGIC INDICATORS (U.S.P.) are defined as specific spores of microorganisms
particularly resistant to a certain sterilization process that are added to a carrier
(strip of filter paper) or to one sample of the load being sterilized.
i. For STEAM: spores of bacillus stearothermophilus
ii. For DRY HEAT/GAS: spores of bacillus subtilis
iii. For IONIZING RADIATION: spores of bacillus pumilus
2. Pyrogen-free: absence of fever-producing organic substances from microbial
contamination (lipopolysaccharide from the outer cell wall of the bacteria and
a) Pyrogens: relatively thermostable products that remain after regular sterilization
processes, such as autoclaving (125°C), dry heat (170°C) and filtration with filter
>0.2µm pore size. Pyrogens can be destroyed with high heat by oxidation or
“burning up”: oxidizing agents (potassium permanganate, peroxides, alkali, acids)
or 250°C for 30-45 minutes. Parenteral preparations are generally made with
pyrogen-free water and chemicals.
b) Validation of Pyrogen-free:
i. RABBIT TEST: change in rectal temperature of 0.5° C in one rabbit or a sum of
1.4 °C in 5 rabbits.
ii. LAL TEST (Limulus Amebocyte Lysate): based on the coagulation of an enzymeprotein complex from red blood cells of the horseshoe crab in presence of
lipopolysaccharides (pyrogens). This test is more sensitive to endotoxins than the
a) Particulate matter refers to mobile, undissolved substances unintentionally present
in parenteral products.
b) Standards related to the number and dimensions of particles in LPS and SVP are
established by USP, depending on the risk level:
i. LPS: not more than 50 particles/ ml that are ≥ 10 µm (50,000/L) OR not more
than 5 particles/ml that are ≥ 25 µm (5,000/L).
ii. SVP: not more than 10,000 particles/container that are ≥ 10 µm and/or 1,000
particles/container ≥ 25 µm. c) Control and detection of particulate matter:
i. Electronic liquid-borne particle counter with a light-obscuration sensor.
ii. Clarity test: the swirling of the contents of a container against a light and dark background under light.
Particles of lint, rubber, other debris: float or settle to the bottom
Air bubbles: rise to the surface and dissipate
Normal human vision: detects particles > 50 µm; also reflective particles
(glass) of 25 µm. PHCY 6100- Teixeira 4 Parenteral Medications and Sterile Fluids
i. The solution itself and chemicals comprising it;
ii. The manufacturing process;
iii. The packaging components;
iv. The devices used for administration; v. The manipulations during preparation.
4. Stability: parenterals regularly have added substances
a) Buffers to keep the pH;
b) EDTA, citric acid, tartaric acid to prevent oxidative processes;
c) Benzyl alcohol, chlorobutanol, benzoates to prevent from microbial and fungal
d) Special packaging components, lyophilization (freeze-dry method), spray-drying. PR EPAR ATION OF INJECTIONS
1. Methods: same used for oral solutions, suspensions and emulsions but with some
• Special purity of solvents and drugs
• Buffers, stabilizers and preservatives are restricted
• Coloring agents are prohibited
• Products must be sterile, pyrogen-free and particulate-free (compendial standards
for particulate matter must be used to avoid thrombus formation and embolism)
• Prepared in controlled areas (strict sanitation, personnel especially trained and
• Packaged in hermetic containers as single-dose or multiple-dose
• Volume in slight excess
• Specific labeling
• Powders for reconstitution packaged as lyophilized forms.
2. Solvents And Vehicles:
• Water for injection, USP (WFI): same as purified water, USP; not required to be
sterile; must be pyrogen-free; no antimicrobial agent; used for manufacturing of
parenterals that will undergo final sterilization.
Sterile Water for injection, USP (SWFI): sterile; pyrogen-free; packaged in singledose containers; no antimicrobial agent; used as diluent for reconstitution of
powders or in parenteral admixture (aseptically added).
Sodium Chloride injection or Normal Saline injection, USP (NS, 0.9% NaCl): sterile;
pyrogen-free; isotonic solution (0.9% NaCl, ~154 mEq of sodium and chloride
ion/liter); no antimicrobial agent.
Bacteriostatic water for injection, USP (BWFI): sterile; pyrogen-free; contain
bacteriostatic agents; packaged in containers of not more than 30 ml; used only
when small volumes are administered due to toxicity of antimicrobial agents (benzyl
alcohol, etc); “Not for use in newborns”. PHCY 6100- Teixeira 5 Parenteral Medications and Sterile Fluids
• Bacteriostatic Sodium chloride injection, USP: 0.9% NaCl; same characteristics as
Ringer’s injection, USP: sterile solution of NaCl + KCl + CaCl 2 in concentration similar
to physiologic fluids; used as vehicle or electrolyte replenisher.
Lactated Ringer’s or Ringer’s lactated: same as Ringer’s injection + Lactate.
Dextrose 5% in Water, USP (D5W): sterile; isotonic solution of dextrose; used to
hydrate patients without addition of salts.
b) NONAQUEOUS: • • USP grade glycerin, polyethylene glycol, propylene glycol, alcohol: used as solvents
for drugs with limited water solubility or susceptible to hydrolysis; must be
nonirritating, nontoxic, non-sensitizing; should allow “syringeability” (not very
Fixed vegetable oils, USP: corn oil, cottonseed oil, peanut oil, canola oil, sesame oil;
must remain clear when stored under refrigeration; must not contain mineral oil or
paraffin; label must list specific oil; used mostly for intramuscular injections. 3. Added substances:
a) Only if necessary to increase stability or effectiveness (buffers, preservatives,
solubilizers, antioxidants, etc).
b) Within a vial of an injectable product the air is customarily replaced with an inert
gas (Nitrogen) to prevent chemical reaction with oxygen. PACK AGING, LABELING, STOR AGE OF PARENTERALS
b) Leaching of constituents
c) Sorption of drugs
d) Transmission of light
e) Alteration during storage
g) Clarity and absence of color (only amber color for light-sensitive drugs)
GLASS: Types I, II, or III. NP type not permitted; heavy, easy to break,
bulky for storage, leaching of alkali from soda-lime glass (Types II and III).
PLASTIC: low and medium density polymers of polyethylene; allows more
variety of shapes and sizes, more resistant to impact, may leach polymer
from plastic additives (plasticizers); more prone to cause binding of drug
molecules to polymer materials; can be used for packaging as well as for
supplies; polypropylene can be autoclaved; polyvinyl chloride (PVC) allows
more rigidity and good clarity but cannot be autoclaved.
i) Single-dose containers: ampuls, bottles, pre-filled syringes; cannot be resealed;
may be packaged as small-volumes or large-volumes. PHCY 6100- Teixeira 6 Parenteral Medications and Sterile Fluids
j) Multiple-dose containers: bottles, bags; contain antibacterial preservatives; allow
withdrawal of several doses; can be resealed; packaged as small-volumes only
(~30 ml to limit number of penetrations and excess of antibacterial agent).
2. Labels: very strict rules apply
a) Placement: must leave sufficient area of container free for inspection of
b) Labeled volume: a slight excess in volume of the contents of ampuls and vials
over the labeled “size” or volume of package is permitted and common practice
because it is impossible in practice to transfer the entire volume of a single-dose
container or the last dose of a multiple-dose container into a syringe.
3. Storage: RT for chemically pure agents; refrigeration for biological products,
vaccines, insulin, some antibiotics, cytotoxic and biotechnology products. DOSAGE FOR M S FOR PAR ENTERAL USE
1. Official Types: defined by USP
__________________ Injection, USP: solutions, fat emulsion.
Sterile ________________, USP: dry solid or liquid concentrate, need to be
reconstituted or diluted, contain no other substance than the drug.
_____________ for Injection, USP: same as previous + other substances.
Sterile ____________ Suspension: solids suspended in vehicle, not for IV and spinal
Sterile _________for Suspension: dry powders, which need addition of suitable vehicles,
not for IV and spinal injection.
2. Injections and Other Sterile Fluids:
a) SVP (Small Volume Parenterals): preparations for direct injection into vein,
muscle, subcutaneous tissue, etc (e.g. insulin, antibiotics, analgesics).
b) LVP (Large Volume Parenterals): solutions (except fat emulsion) for intravenous
infusion only; contain no antibacterial; used for replenishment of body fluids and
electrolytes or to provide nutrition; single-dose containers with volumes varying
from 150 ml - 1000 ml.
i. Types of LPS:
• Maintenance Therapy: for patients entering or recovering from surgery or
unconscious. • Replacement Therapy: patients with heavy loss of fluid and /or electrolyte
(severe diarrhea, vomiting). • Water Requirement: water is administered in a solution with Dextrose or
electrolytes (avoids hemolysis). PHCY 6100- Teixeira 7 Parenteral Medications and Sterile Fluids
• Electrolyte Requirement: potassium (cardiac and skeletal muscle function)
is used for Hypokalemia during severe burns, GI diseases, acute
alcoholism, poor nutrition; sodium (principal extracellular cation) is used
for Hyponatremia during excessive sweating, diarrhea, use of some
diuretics; chloride (principal extracellular anion, necessary for muscle
contraction and to maintain acid-base balance); • Calcium, Magnesium, Iron are also lost but not replaced during short-term
parenteral therapy. • Caloric Requirement: D5W is used to maintain basal caloric requirements,
reduce caloric deficit and minimizes breakdown of proteins (a 70 Kg fasting
patient loses ~80 g/day of protein). • Parenteral Nutrition (Hyperalimentation): infusion of large amounts of basic
nutrients (amino acids, high concentration of dextrose, electrolytes,
vitamins, fat ) for patients unable to get oral or enteral nutrition. • Enteral Nutrition: nasogastric, gastrostomy or transpyloric routes useful for
bedridden patients who are not physically active, post-surgical patients or
cancer patients with very poor appetite. • Blood Replenishment: whole blood, red blood cells, serum albumin, plasma
protein fraction, etc. • Pellets or Implants: sterile small solids implanted subcutaneously (thigh or
abdomen) with especial injectors or by surgical incision; has long-lasting
effect (50x - 100x the usual dose used by other routes); some hormones
are used as implants (corticosteroids, estrogens, testosterone). • Irrigation Solutions: not used by injection, these solutions are used during
surgical procedures to wash blood and debris or to wash wounds. • Dialysis solutions: used for peritoneal dialysis or hemodialysis for removal
of toxic substances (poisoning, kidney failure, before renal transplants)
from blood or peritoneal cavity. PHCY 6100- Teixeira 8 ...
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- Fall '10