Parenteral Medication

and Sterile Fluids

Dr. Misbah Sultana

Injections

• Injections are sterile, microorganism and

pyrogens free preparations intended to be
administered parenterally.

• The term parenteral refers to the injectable

routes of administration.
• The word parenteral has been derived from the
two Greek words “Para” means outside or
away from “Enteron” means intestine.

• The meaning of parenteral means outside of

intestine or it denotes the routes of
administration other than oral route.
Pyrogens
• Water used in parenteral and irrigating
solutions (To clean part of body) should be free
of pyrogens.

• Pyrogens are the products of metabolism of

microorganisms. Most bacteria, molds and
viruses produce pyrogens.
• The gram negative bacteria produced the most
potent pyrogenic substances.

• Chemically pyrogens are lipid substances which

are associated with a carrier molecule which is
usually a polysaccharide or may be a protein.
• Pyrogens produce
• Rise in body temperature ,
• Chills ,
• Body aches,
• Vasoconstriction
• Rise in BP.
Methods to Remove Pyrogens
1. Distillation

2. Reverse osmosis

3. Heating at 180C for 3 to 4 hours.

4. By adsorption on surface of selected adsorbent.

Parenteral Route of Administration
(Add Assignment)

1. Intravenous

2. Intramuscular

3. Subcutaneous route

4. Intradermal route
Official Types of Injection
• According to USP Injections are separated to five
distinct types and generally defined as follows:-

1. Medicaments or solutions or emulsions

suitable for injections.

• Example:- Insulin Injection USP.

2. Dry solids or liquid concentrations containing
no buffers , diluents or other added substances
and which upon addition of suitable solvents
yield solutions conforming in all aspects to
requirements for injections.

• Example:- Sterile Ampicillin Sodium USP

3. Preparation which are same as those describe
in two types except that they contain one or
more buffers, diluents or other added
substances.

• Example:- Methicillin Sodium for Injection USP

4. Solids which are suspended in suitable fluid
medium which are not to be injected
intravenously or into spinal canal. (They are
injected intra articular)

• Example:- Sterile Dexamethasone acetate

Suspension USP
5. Dry solids which upon addition of suitable
vehicle yields preparation confirming in all
aspects to the requirement for sterile
suspension.

• Example:- Sterile Ampicillin suspensions for

injections USP.
Add here your assignment

Added Substances used in Parenterals

Solvents and Vehicles for Injection

1. The most frequently used solvents in the

large scale manufacturing of injection is
water for injection .This water is purified by
distillation or reverse osmosis and contain
total solids not more than 1mg/100ml.
2. Water for injection USP may not contain
added substances and it must be pyrogen free.

3. Water for injection should be stored in tight

containers at temperature below or above the
range in which microbial growth occur.

4. The water should be collected in sterile and

pyrogen free container and containers are
usually glass or glass lined.
Types of Solvents

1. Aqueous Solvent
2. Non aqueous solvents
 1. Aqueous Solvent
1. Sterile water for injections, USP
2. Bacteriostatic water for injections,USP
3. Sodium Chloride Injection, USP
4. Bacteriostatic Sodium Chloride Injection, USP
5. Ringer’s injection, USP
6. Lactated Ringer’s injection USP
1. Sterile water for injections
• It is water for injection which has been
sterilized and packaged in single dose container
of not greater than 1 liter size.

• As water for injection, it must be pyrogen free

and may not contain antimicrobial agent or
other added substances.
• They are used for reconstitution of multiple
antibiotics.

• In use, this water is aseptically added to vials to

prepare the desired injection.

• Example :- A suitable injection may be prepared

from the dry powder, e.g; Sterile Ampicillin
Sodium USP, by the aseptic addition of sterile
water for injection.
2. Bacteriostatic water for injections

• It is a sterile water for injection containing one or more

suitable antimicrobial agents.

• It is packed in prefilled syringes in vials containing not

more than 30 ml of water.

• The container label must state the name and proportion

of antimicrobial agent which is present.
• This water is employed as a sterile vehicle in
preparation of small volume of the injectable
preparation.

• Its use in parenterals which are administered in large

volume is restricted due to excessive and toxic
amount of antimicrobial agent which would be
injected along with medication.
3. Sodium Chloride Injection USP
• It is sterile isotonic solution of sodium chloride in
water for injection. It contains antimicrobial agents.
The Na+ and Cl- ions content of injection are
approximately 154 mEq. of each per liter.

• The solution may be used as a sterile vehicle in

preparation of solutions or suspensions of drugs for
parenteral administration.
4. Bacteriostatic Sodium Chloride
injection USP
• It is sterile isotonic solution of sodium chloride in
water for injection.

• It contain one or more suitable antimicrobial agents

which must be specified on the label.

• NaCl is present at 0.9 % concentration to render the

solution isotonic.
• This solution may not be packed in container
greater than 30 ml inside.

• USP labeling requirements demand that the

label must state that “ Not for use in newborn”
due to toxicity of bacteriostatic agent e.g.
benzyl alcohol.
• This toxicity may result from high cumulative
amount( mg per kg ) of benzyl alcohol and
limited detoxification capacity of newborn or
neonate liver.

• This solution does not cause problems in

children and adults.
5. Ringer injection USP
• It is sterile solution of NaCl ,KCl and Calcium
chloride in water for injections.

• Three agents are present in concentration

similar to that which is found in physiological
fluid.
• It is employed as a vehicle for other drugs or
alone as an electrolyte replenisher or fluid
extender.

• For Example:-blood loss, Trauma, burns.

6. Lactated Ringer injection USP
• Whenever these solutions are prepared, It has different
quantities of same three salts as in ringer injection but it
also contain Sodium Lactate.

• This injection is used as fluid extender.

• Uses
• As an electrolyte replenisher
• As systemic alkalizer
7. Non aqueous solvents
1.Due to limited water solubility of medicinal
substances or due to the hydrolysis. Pharmaceutical
formulation must be use non aqueous vehicle.

2. The selected vehicle must be non-irritating , non-

toxic and non-sensitizing in the amount which is
administered.
3. It must not exert its own pharmacological action
and must not affect the activity of medicinal agents.

4. Among many considerations the important are

A. the solvents physical and chemical stability at

various PH levels.

B. Its viscosity which must be such as to allow ease of

injection.
C. Its fluidity must be maintained over a wide
temperature range.

D. Its boiling point which should be sufficiently

high to permit heat sterilization.

E. Its miscibility with the body fluids.

F. Its constant purity or ease of purification and
standardization.

5. Non aqueous solvents include fixed vegetable oil,

glycerin, polyethylene glycol , propylene glycol,
alcohol, and number of agents which are lesser
used are e.g. ethyl oleate , dimethyl acetamide.
6. These agents are saved in amounts
administered and don’t interfere with
therapeutic efficacy of preparations.

7. The oil must not contain mineral oil or paraffin

as these materials are not absorbed by body
tissue.
8. Although the toxicities of vegetable oils are generally
considered to be relatively low, some patients exhibit
allergic reactions to specific oils.

9. Therefore , when vegetable oils are employed in

parenteral products, the lable must state the specific oil
present.
10. The most commonly used fixed oils in injectins are
corn oil, cottonseed oils, peanut oil, and sesame oil.

11. Castor oil and olive oil have been used in occasion.

12. Mostly, oleoginous injections are administered I/M.

 INJ. OIL CATEGORY

Dimercaprol Inj. Peanut Antidot to arsenic,

gold, mercury poisoning

Estrone Inj. Sesame Estrogen

• INJ. OIL CATEGORY

Progesteron in oil Inj. Sesame Progestin

Testosterone Cypionate Inj. Cottonseed Androgen

QUALITY Control test for Injectables
• Pyrogen test
• Sterlity tedt
• pH
• isotonicity
• Clarity test
• Leakage test