GROUP 5: April 26, 2019

Bacani, Ana Paula

Go, Lance Emmanuel
Ocaña, Franchesca Nicola
Ulep, Jant Nicole Joyce

PARENTERAL DRUG DELIVERY

|| INTRODUCTION

Enteral administration is the term used to describe drug administration via the
gastrointestinal tract. Majority of medicines are administered orally via this route. It can
be in the form of tablets, capsules or liquids. The enteral route also encompasses rectal
administration utilizing dosage forms such. It can be in the form of suppositories,
enemas or rectal ointments.
On the other hand, parenteral administration literally means any method of drug
administration, which does not utilize the gastrointestinal tract, such as by inhalation, or
application to the skin. It commonly means drug administration by injection.
There are certain reasons why parenteral route of administration may be chosen
by the clinicians or the manufacturer of a medicine. The routes available for parenteral
administration and the tissues, organs and anatomical spaces that can be accessed by
injection are outlined.

Outline:
I. Reasons for choosing parenteral administration
II. Routes of parenteral administration
III. Official types of injections
IV. Pharmacopoeial requirements
V. Absorption from injection sites
VI. Excipients
VII. Containers

I. REASONS FOR CHOOSING PARENTERAL ADMINISTRATION

Almost all patients would prefer to receive their medication orally or topically
rather than receive treatment via injections. Injections are painful and stressful (some
have needle phobia). Also, from a manufacturer’s point of view, it is often simpler and
much cheaper to prepare medicines such as tablets or liquids. It has lesser
requirements for manufacturing premises for these non-sterile products.
However, there are clinical advantages associated with parenteral administration.
Many medicines are administered parenterally simply because drug molecule itself
would be rapidly broken down in GIT and would therefore become inactivated before it
is absorbed into the circulatory system.
Examples: aminoglycoside antibiotics, such as Gentamicin
 The injectable route may be chosen to provide a highly localized effect. This is
particularly true when the injection route accesses a particular anatomical area or organ
system.
Examples: steroid injection, intra-articular injection, intra-ocular injection or
intrathecal injection

Intravenous injection delivers the drug directly into the circulatory system, where
it is then rapidly distributed around the body. This is important clinically as the drug will
rapidly produce an effect, whereas peak blood levels may not be achieved for one to
two hours after a drug is administered orally.
This rapid onset of action for an intravenously administered drug may be critical
in emergency situations. Intravenous injection is routinely used to administer medication
to the unconscious patient who is unable to swallow. This route is also for those patients
whose GIT is not working.
Examples: fluids for hydration, electrolyte replacement, total parenteral nutrition

In Intramuscular injection, the release of the medicine from the injection site into
the circulation can be delayed and prolonged.

II. ROUTES OF PARENTERAL ADMINISTRATION

The purpose of the treatment and the volume of medicine to be administered

usually govern the choice of route.

A. INTRAVENOUS INJECTIONS AND INFUSIONS

➔ Administered into an easily accessible prominent vein near the surface of
the skin, typically on the back of the hand or in the internal flexure of the
elbow
➔ The volumes administered can range from 1 mL for an IV injection, up to
several litres for an IV infusion
➔ IV injection: rapidly increases the concentration of the drug in the plasma
and produce a rapid effect
➔ IV infusion: slow and controlled rate, often utilizing a pump, the drug
enters the circulation at a much slower and controlled rate
➔ By altering the infusion rate, it is possible for the clinician to titrate the
dose against the effect required ex: controlling blood pressure, by
manipulating the infusion rate (ex: of dobutamine)
➔ Drug solutions at high or low pH or highly concentrated hypertonic
solutions will damage the cells lining the vein, causing localized pain and
inflammation (thrombophlebitis)
➔ To avoid this problem, a central line may be inserted.
➔ Central line: a long, indwelling catheter inserted into a vein in the neck or
forearm with the end of the catheter sited in the superior vena cava close
to the right atrium of the heart.
➔ Medicines administered IV, via a central line, become rapidly diluted in a
large volume of blood and do not cause local irritation to the blood vessel.
 ➔ NOT IN IV ROUTE: water in oil emulsions or suspensions; This is
because the suspended drug particles can physically block capillaries and
the oil phase of W/O injection could cause a fat embolism, again blocking
blood vessels.

B. INTRA-ARTERIAL AND INTRACARDIAC INJECTIONS

INTRA-ARTERIAL
➔ Essentially the same as IV administration except that the drug is
administered into an artery rather than a vein
➔ Arteries are not as readily available veins, and this technique is much
more invasive, and carries a greater risk than simple IV administration
➔ It is seldom used
➔ Sometimes used when intravenous access cannot easily be established,
such as in very premature infants, due to the very small size of their veins
in relation to the catheter tubes used to maintain vascular access.
➔ Also used in treatment of some cancers (such as liver cancer) where the
anti-cancer medicines are injected into an artery upstream of the tumor
site to ensure the maximum amount of drug reaches the tumor before
distribution elsewhere around the body
➔ The benefits of this method do not appear to outweigh the risks to any
significant degree
INTRACARDIAC
➔ Used to administer a drug (a common example being an aqueous solution
of adrenaline) directly into either cardiac muscle or into a ventricle of the
heart
➔ This is undertaken only in life threatening emergencies to produce a rapid,
local effect in the heart during a heart attack or in circulatory collapse

C. INTRADERMAL INJECTIONS
➔ Given into the skin between the epidermal and dermal layers
➔ Volumes of up to 0.2 mL can be given by this route and absorption from
the ID injection site is low
➔ Used for immunological diagnostic tests, such as allergy tests, or the
injection of tuberculin protein to determine immunity against tuberculosis.
➔ Some vaccines such as BCG (tuberculosis) are administered by ID
injection

D. SUBCUTANEOUS INJECTIONS
➔ Also called hypodermic injections
➔ Administered into the loose connective and adipose tissues immediately
beneath the dermal skin layer
➔ Typical injection sites are the abdomen, upper arms, and upper legs
➔ Volumes of up to 1 mL can be administered comfortably, and aqueous
solutions or suspensions are administered via this route
➔ As this tissue is highly vascular, drugs administered by this route are fairly
rapidly and predictably absorbed from this site
 ➔ Ex of drug administered via this route: INSULIN

E. INTRAMUSCULAR INJECTIONS
➔ Aqueous or oily solutions or suspensions can be administered in
volumes of up to 4 mL
➔ In adults, the site for larger volume injections is the gluteal muscle.
➔ In children, the site for larger volume is the thigh muscle.
➔ It is slowly absorbed from the injection site into the systemic circulation
compared to subcutaneous route.

F. INTRASPINAL INJECTIONS
➔ Given between spine vertebrae into spinal column area. (Aqueous solution
only)
➔ INTRATHECAL- CSF in subarachnoid space used for spinal anaesthesia
(not diffuse in blood brain barrier)
➔ E.g. meningitis antibiotics or anticancer agents (methotrexate or
cystarabine) Volumes up to 10 mL
➔ INTRACISTERNAL - between atlas & axis vertebrae into cisterna magna
(antibiotic & diagnostic purposes)
➔ EPIDURAL/INFUSIONS - peridural space between the dura mater and the
vertebrae. (spinal anaesthesia for childbirth)

G. INTRA-ARTICULAR INJECTIONS
➔ Given to synovial fluid of joint cavities. (Knee)
➔ It is in the form of aqueous solutions or suspensions.
➔ Produces a local effect.
➔ Anti-inflammatory drugs to treat arthritic conditions or sports injuries.

H. OPHTHALMIC INJECTIONS
➔ INTRAOCULAR- into the eye and furthered classifies as:
➔ INTRACAMERAL - anterior chamber of eye (0.1-1 mL) antibiotics or local
anaesthetics (cataract surgery).
➔ INTRAVITREAL - vitreous chamber (0.1 mL max) raising intraocular
pressure can damage retina; used for various ocular diseases.
➔ SUBCONJUNCTIVAL - under conjunctiva (1 mL or less).

III. OFFICIAL TYPES OF INJECTIONS

1. For Injectable Suspension

- Formed through addition of a suitable solvent that conforms to the
requirements for suspension for injection.
2. Injectable Suspension
- A liquid preparation of solid suspended substance in a suitable liquid
medium.

3. Injectable Emulsion
 - A liquid preparation of a drug substance dissolved or dispersed in in a
suitable emulsion medium.

4. For Injection
- Formed through addition of a suitable solvent that conforms to the
requirements for solution for injection.

5. Injection
- A liquid preparation that contain drug substances or solutions (nutrition and
water).
- Could be packed in Pre-Filled Pens, Syringes or Vials.

IV. PHARMACOPOEIAL REQUIREMENTS

A. GENERAL REQUIREMENTS

1. Sterility
- Sterile preparations intended for injection, infusion or implantation into the
body.
- Sterility requirements is vital as the method of administration of these
products bypasses the body’s natural defense systems and barriers, and
introduces the medicine directly into the bloodstream or other body
tissues.

2. Excipients
- Should not adversely affect the action of drug substance, or cause any
side effects or toxicity at the concentrations used in a given formulation.
- Made isotonic in relation to human blood,
- Made to adjust pH and increase solubility of drug substance,
- Include preservatives that increase stability of drug substance & increase
shelf-life
3. Containers
- Materials sufficiently transparent to allow contents to be visually inspected
for particles, prior to use and can be made from glass or plastic.
- Effectively sealed to prevent enclosed medicine becoming contaminated.
- Airtight and also be tamper evident
4. Endotoxins and Pyrogens

- Free from endotoxins and pyrogens. Bacterial products that maybe

released from certain types of bacteria when they are alive, or after they
die. May be present in sterile products as a by-product of the sterilization
process which kills the bacteria during manufacture.
- When injected, can cause fever, and even shock if present in sufficient
quantities.
- Parenteral products must comply with the test for bacterial endotoxins or
the test for pyrogens
5. Particulates

- Final general test for compliance is for particulate contamination.

- The test must be free of visible particles and contain only very low
numbers of sub-visible particles and contain only very low numbers of
sub-visible particles.
- Particles inadvertently injected can result to pulmonary embolism.
- European Pharmacopoeia- 10 & 25 µm particles per container of
injectable product.
- Suspensions- intramuscular, intra-articular or subcutaneous.
- Emulsions- intravenous (max droplet size link to capillary diameter usually
less than 3 µm)

B. CATEGORY-SPECIFIC REQUIREMENTS

1. Injections
- Include sterile solutions, emulsions or suspensions.
- Prepared by dissolving, emulsifying or suspending the drug substance
together with any required excipients, in water or non-aqueous liquid or a
mixture of aqueous and non-aqueous vehicles.
- Solutions are clear and free from visible particles
- Emulsions must not show any signs of phase separation in other words
creaming or cracking.
- Suspension must be sufficiently stable to allow uniform dose
- Aqueous injections designed for multiple dosing must contain an
antimicrobial preservative, unless it is sufficient to be self-preserving. It
must not exceed more than 15 mL.
2. Infusions
- Sterile aqueous solutions or emulsions with water as the continuous
phase. They are usually made isotonic with respect to blood.
- Large volume parenterals, typically between 100 mL to 1000 mL, but may
be larger.
- Infusions do not contain antimicrobial preservatives.
- Solutions are clear and free from visible particles.
- Emulsions possess no sign of phase separation.

3. Concentrates for Injection or Infusion

- Concentrates for injection or infusion are sterile solutions intended for injection or
infusion only after dilution.
- These are then diluted to a prescribed volume usually with an aqueous liquid
 such as saline (0.9 % w/v sodium chloride) or water before administration.
- After dilution, they comply with the requirements for injections or infusions given
above.
4. Powders for Injection or Infusion
- These are dry solid, sterile substances sealed in their final container.
- When dispensed, a volume of the prescribed sterile diluent (usually an aqueous
liquid) is added and shaken with the powder rapidly forming either a clear,
particle-free solution or a uniform suspension.
- Freeze-dried (lyophilized) products for parenteral use are considered to be
powders for injections or infusion. Often used for for drug substances that are not
stable in solutions (e.g. degrade by hydrolysis)

V. ABSORPTION FROM INJECTION SITES

Movement of drug from the site of administration or the injection site into the
bloodstream. There is no absorption process when a drug is injected intravenously into
bloodstream or into a similar fluid of distribution such ascerebrospinal fluid (intrathecal
and intracisternal injections), or directly into thesite of action (intra-articular or
intraocular injection).

Drugs that are injected intradermally, subcutaneously or intramuscularly must

undergo absorption to reach systematic circulation. This happens by diffusion of the
drug to the tissues surrounding the injection site followed by penetration through the
walls of blood capillaries. Intradermal injection are usually in solution, and is often used
for diagnostic purposes and act locally at the site administration.

Subcutaneous and Intramuscular injections can either be solution or suspension.

Absorption of aqueous solution is usually complete within 30 minutes, delay of
absorption depends on subcutaneous fatty tissue. While fairly rapid absorption of
aqueous injection to these sites depends on an unimpaired blood flow surrounding
injection site.

Vasoconstrictors (adrenaline) may be incorporated to other drugs to prolong

their retention at the injection site.
Examples:
a. Local anesthetic – dental surgery
b. Proteins and peptides – insulin
c. Colloidal particles – injectable iron complexes is absorbed
through lymph vessels, the speed of lymphatic flow is increased by
massaging the injection site for subcutaneous injection
Formulation factors

Drug absorption from a suspension is much slower than a solution injected in the
same site thus slow and prolonged release from site of action can be used to reduce the
frequency of dosing. Drug salts with low aqueous solubility may be specifically chosen
for intramuscular injection to provide prolonged effect. Ex. Benzathine penicillin for
syphilis and corticosteroids such as hydrocortisone acetate and traiamcinolone
acetinide. Corticosteroids in aqueous suspension is injected into joint spaces
(intraarticular) to prolonged anti-inflammatory action.

The rate of release of a drug suspension is governed by the solubility of the drug
in the tissue fluids and the surface area of the suspended drug particles. Difference in
particle size and crystal structure can alter the absorption rate from subcutaneous
injection site this has been employed with Insulin to give a range of insulin with different
time for the onset and different durations of action. Soluble insulin a short acting,
injected 15 to 30 minutes prior to eating, Intravenously – used in response to diabetic
emergencies (diabetic ketoacidosis). Isophane insulin an intermediate acting,
suspension of soluble insulin complexes with protamine sulphate (protamine complex
forms rod shaped crystals) while Zinc suspension a long acting insulin, mixture of
amorphous crystals dissolve rapidly than regular crystals.

Oily intramuscular injection can either be solutions or suspensions, often

steroids, hormones or fat soluble vitamins in metabolized oil (arachis or sesame as
vehicle). Used to administer drugs that are insoluble in water, or water soluble drug
substances can be chemically modified to produce an oil soluble compound for
administration in an oily Injection. Oily injections are more viscous than aqueous
injections, thus release of drug from oily intramuscular injections is very slow, and is
often used for many antipsychotic medicines as they require dosing only every 2 to 4
weeks rather than daily oral dosing.

VI. EXCIPIENTS
Aids the dissolution or suspension of the drug in the vehicle. It is
Incorporated to comply with pharmacopoeial requirements for multiple use. Often
included in parenteral products to prevent, reduce or delay the degradation of drug
product over time thus improving product’s shelf-life and it also adjust pH (comparable
to the physiological pH) and tonicity (comparable to plasma values) of the product this is
to reduce pain and irritation caused by administration process. Solubilizers and co-
solvents are the most widely employed excipients in the formulation of parenterals

Solvents and Vehicles for Injections:

● Aqueous Vehicles

1. Water for Injection USP.

- Most frequently used solvent in large-scale manufacturing
- Water is purified through distillation or reverse osmosis process.
 - It is not required to be sterile but is required to be pyrogen-free.
- This water is used for the manufacture of injectable products that needs to
be sterilized after production.
- Should be stored in tight containers and in temperatures that are below or
above the range which microbial growth occurs.
- Containers are usually glass or glass-lined.

2. Sterile Water for Injection USP.

- Required to be sterile and pyrogen-free but with an allowable amount of
endotoxin level (not more than 0.25 USP EU/mL).
- It may not contain any anti-microbial agent or added substance.
- It is intended for use as a solvent, vehicle or diluent for packaged
injectable preparations that are already sterilized.
- They are used in the reconstitution of multiple antibiotic medications.
- Aseptically added to the vial of medication, as means of preparation.
- Packaged in single-dose containers not > 1 L.

3. Bacteriostatic Water for Injection USP.

- It contains one or more suitable antimicrobial agents.
- Usually packaged in pre-filled syringes or in vials containing not more than
30 mL of water.
- Label should state the antimicrobial agents used.
- Usually used as a sterile vehicle in preparations of small volumes of
injectable preparations.
- “NOT FOR USE IN NEONATES” should be stated so as to prevent
Benzyl Alcohol poisoning in infants (gasping syndrome).

4. Sodium Chloride Injection USP.

- Also known as sterile isotonic solution of Sodium Chloride in water for
injection.
- Contains no antimicrobial agents but with 154 mEq each of Sodium and
Chloride ions per liter.
- May be used as a vehicle in solution or suspension for injection.
- It is also used as a catheter or IV flush to maintain patency; and also,
infusing liquids, addition of IV medications and extraction of blood.
- 2 mL is usually used to flush the line after each use or every 8 hours.

5. Bacteriostatic Sodium Chloride Injection USP.

- Contains one or more antimicrobial agents that must be specified on the
label.
- May not be packaged in containers larger than 30 mL.
- Care must be observed to ensure compatibility of the drug with the
preservatives and Sodium Chloride.
- Also used to flush catheter or IV line to maintain patency.
- “NOT FOR USE IN NEONATES” should also be stated so as to prevent
Benzyl Alcohol poisoning in infants.
 6. Ringer’s Injection USP.
- Contains Sodium Chloride, Potassium Chloride and Calcium Chloride in
water for injection, and these agents are present and same as of
physiologic fluids.
- Used as a vehicle for other drugs or used as an electrolyte replenisher
and plasma volume expander.
7. Lactated Ringer Injection USP
- Ingredients are same as of Ringer’s Injection USP, added only with
Sodium Lactate.
- Used as a fluid and electrolyte replenisher, and as a systemic alkalizer.

● Non-aqueous Vehicles

Oleaginous injections are administered intramuscularly and must not be

administered intravenously, as the oils will occlude the pulmonary microcirculation.
Selected vehicle must be non-irritating, nontoxic, non sensitizing, does not exert
pharmacologic activity nor may adversely affect the activity of the medicinal agent.

Among the many considerations are the solvents physical and chemical stability
at different pH levels, viscosity, must be maintained over a fairly wide temperature
range, miscibility with body fluids and constant purity or ease of purification and
standardization.

1. Fixed vegetable oils

- Must remain clear when cooled to 10oC to ensure the stability and clarity
of product during refrigeration.
- Must not contain mineral oil or paraffin (not absorbed by body tissues)
- Toxicity of vegetable oils are relatively low but exhibit allergic reactions to
some patients
- Commonly used for injections are corn oil, cottonseed oil, peanut oil, and
sesame oil.

2. Alcohols, Glycerine, Polyethylene glycols, Polypropylene glycol

ADDED SUBSTANCES

USP permits addition of suitable substances to official preparations intended for

injection to increase stability or usefulness as long as it does not interfere with the
therapeutic efficacy of the preparation.

Preservatives:
- Added to injections design for multiple dose.
- Packaged in glass vials or cartridges with synthetic rubber septum that
can be punctured on a number of occasion
- Inhibits growth of any microorganism that is introduces in the product
during repeated use
- Ethanol (10% v/v), Glycerol (10-20% v/v) and Propylene Glycol ( 15-30 %
v/v) are added to a formulation as co-solvents also will provide an
antimicrobial effect.
- Agents containing mercury in concentration not more than 0.01%
- Cationic surface compounds in concentration of 1.01%

Antioxidants:
- Reduces the rate of degradation in the product to improve shelf life or
expiry date.
- Nitogen is bubbled through solution containing the drug prior to filling into
the final packaging, displaces any dissolved oxygen from the drug solution
also known as Sparging.
- Most commonly used antioxidant are the sulphite salts with concentration
of 0.2%
a. Sodium metabisulphite – acidic parenteral products
b. Sodium bisulphite - neutral parenteral products
c. Sodium sulphite - alkali parenterals

1. Water soluble
Chemicals with lower oxidation potential than the drug thus reacts
with oxygen present in the product. Examples are Sulfurous acid salts,
Ascorbic acid isomers, Thiol derivatives
2. Oil soluble
Butylated hydroxyanisole (BHA) – can be used in Intramuscular
injection and Intravenous injection and Alpha Tocopherol – highly
lipophilic (for oil based parenteral products)
pH Adjustment and Buffers:

pH between 3.0 and 9.0

- This is the ideal pH value for injectable products prior to administration.
- Values above or below this range would cause tissue damage to the site
of administration and is too corrosive.
- Could be adjusted with the addition of acidifying agents such as
Hydrochloric, Citric and Sulfuric Acids; and alkalizing agents such as
Sodium Bicarbonate, Sodium Citrate and Sodium Hydroxide.

Buffers
- Included in the parenteral formulations so as to maintain the pH value at
optimum level.
- Changes may arise due to the interaction of the ingredient in the container
and formulation.
- Examples of buffers include Citric Acid, Sodium Citrate, Sodium
Lactate and Monobasic & Dibasic Sodium Phosphate

Tonicity Adjusting Agents:

- Common tonicity-adjusting agents include Electrolytes (Sodium
Chloride), Glycerin and Monosaccharides or Disaccharides.
- These are usually employed so as to prevent a Hypotonic (lower
osmotic pressure, blood cells will burst) solution, in which could be
solved by the addition of Sodium Chloride, Dextrose and Mannitol and a
Hypertonic (higher osmotic pressure, crenation would be observed
in blood cells) solution, in which could be addressed by dilution prior to
administration.

Cryoprotectants and Lyoprotectants:

- Substances that protect parenteral preparations from adverse freezing or
drying of the product during freeze-dry processing.
- Non-reducing Sugars (Sucrose, Trehalose), Amino Acids (Glycine,
Lysine), Polymers (Liquid PEG, Dextran) and Polyols (Mannitol,
Sorbitol) are examples.

Suspending Agents:
- Parenteral preparations that are usually presented as suspension for
injection requires suspending agents so as to ensure that the drug is
readily and equally suspended prior to administration.
- Methylcellulose is one example that is usually used in intramuscular and
intra-articular injectable suspensions.
- Polysorbate is used as a surfactant in a suspension formulation to ensure
uniform formulation of the suspended drug substance.
 VII. CONTAINERS AND PACKAGING

Containers:

1. Glass
➔ Usual preparations that utilize this type of container are ampoules, vials and
other parenteral preparations.
➔ Type 1 (Neutral Glass) - It is resistant to hydrolysis due to the chemical
composition of the glass used and also known as borosilicate glass.
➔ Type 2 (Treated Soda Lime Glass) - It is more resistant to hydrolysis due to
surface treatment.
➔ Type 3 (Regular Soda Lime Glass) - It is only moderately resistant to hydrolysis
and should only be used in non-aqueous liquid preparations and powders for
injection.

2. Plastic
➔ Usually used by preparations that has 1-liter capacity or more.
◆ Ranges from 100 mL up to 3000 mL.
◆ Preparations include parenteral nutrition bags (peripheral)
➔ Collapsible Bag is the most common form of plastic container, they are
manufactured from PVC and Polyolefin; they also have an additive port for the
addition of other medications.
◆ Collapses when the contents are removed, thus does not require an air
inlet system to equilibrate the inner and outer air.
◆ Drugs with incompatibilities may be absorbed or react with the plastic.
◆ Polyolefin is much less reactive than PVC.
➔ Semi-rigid Plastic Containers are usually made from Polyethylene, they also
have an additive port; but they require air equilibration as they do not fully
collapse.

Packaging:

1. Single-Dose Containers:
- A hermetic container that contains a single-dose of the drug that is given
parenterally.
- Cannot be resealed after use.

2. Multiple-Dose Containers:
- It allows the administration of the drug in multiple doses that is given
parenterally.

Examples of Innovative Parenterals:

Pre-Filled Syringes:
- Medication is already stored in a syringe, without the need for
reconstitution.
 - Needle is already attached to the syringe.
- Prevention of reuse and transmission of blood borne diseases.

Pre-Filled Pens:
- Same as with prefilled syringes, but comes in a form of a ballpen or pen.
- Smaller gauge of needle is usually employed, sometimes needles are
attached and automatically releases when giving the dose.
- Sureclick Autoinjector, Solostar, Sureclick, Flexpen, Kwikpen and
Nordilet are commercial examples of pre-filled pens.

Act-O-Vial:
- Powder is attached at top with solvent at bottom.
- Through pressing on the plastic cap, powder and solvent is mixed.
- Dual-Component System

Triple Chamber Bag:

- Usually composes of Dextrose, Lipids and Amino Acids & Electrolytes.
- For Parenteral Nutrition use only.

ADDITIONAL SECTION: STERILIZATION

Sterilization:
1. Steam Sterilization
➔ Conducted in a pressurized vessel called an autoclave.
➔ The steam released must be pure and saturated with no air and non-
condensable air.
➔ Bowie-Dick Tape is placed to indicate if an adequate steam penetration
occurred.
➔ The greater the pressure is applied, the higher temperature obtainable and
therefore, less sterilization is needed.
➔ Most Autoclaves operate at 121 degrees Celsius or 250 degrees Fahrenheit.
➔ This applicable to parenteral preparations that can withstand the required
temperatures that can be penetrated but is not affected by moisture.
➔ Solutions in sealed containers such as ampoules are readily sterilized during this
process.
➔ Not useful for oleaginous preparations.

2. Dry Heat Sterilization

➔ Usually processed in ovens that are powered by either gas or electricity.
➔ Higher temperatures and longer periods of exposure is needed so as to prevent
microbial growth.
➔ Usually conducted at 150 degrees Celsius to 170 degrees Celsius.
➔ Fixed Oils, Glycerin, Petroleum products are sterilized using this process.
➔ Choice of method when dry containers are required or in handling of dry
chemicals or nonaqueous solutions.

3. Sterilization by Filtration
 ➔ Utilizes Sieving Mechanism so as to remove microorganisms by adsorption on
the filter medium.
➔ It is used for heat-sensitive solutions.
➔ Preparations that underwent this process should undergo extensive validation so
as to make sure that the effectiveness of the filtered preparation is not greatly
influenced by the microbial load.
➔ 14-0.25 micrometers are the ideal sizes for filters.

4. Gas Sterilization
➔ Utilizes Ethylene Oxide or Propylene Oxide Gas to provide better sterilization to
both heat and moisture-sensitive materials.
➔ It is used to sterilize heat-labile enzyme preparations and other antibiotics.
➔ Reduction in exposure time is observed in the process, and is inducted by
increasing its relative humidity by 60% and increasing its exposure temperature
by 50 to 60 degrees Celsius.

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