sterilzaion

8/14/2019 STERILZAION

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Tarun K. Mandal, Ph.D.

STERILIZATION



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STERILIZATION

STERILITY: Absence of life or absolute

freedom from biological contamination.

STERILIZATION: Inactivation orelimination of all viable organism and their

spores.


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STERILIZATION

DISINFECTANT: Substance used on non-living

objects to render them non-infectious; kills

vegetative bacteria, fungi, viruses but Not Spores.

e.g. Formaldehyde


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STERILIZATION

BACTERICIDE (GERMICIDE): Substance

that kills vegetative bacteria and some

spores

BACTERIOSTAT: Substance which stopsgrowth and multiplication of bacteria but

does not necessarily kill them. Growth

usually resumes when bacteriostat

is removed.


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STERILIZATION

ANTISEPTIC: Substance used to prevent

multiplication of microorganism when

applied to living systems. An antiseptic

is bacteriostatic in action but notnecessarily bacteriocidal.



STERILIZATION

VEGETATIVE CELL: Bacterial cell

capable of multiplication (as oppose to

spore form which cannot multiply). Less

resistant than the spore form.

SPORE: Body which some species of

bacteria form within their cells which is

considerably more resistant than thevegetative cell.



STERILIZATION

Methods:

1. Steam Sterilization

2. Dry heat sterilization

3. Filtration

4. Gas sterilization

5. Irradiation

NOTE: End products must pass sterility tests.


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STERILIZATION

DRY HEAT STERILIZATION:

Equipment: Oven

Method:

Dry heat sterilization is carried out at 160 deg C. to

170 deg C. for 2 to 4 hrs. Application:

Glassware

Fixed oils Thermostable powders


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STERILIZATION

Advantages & Disadvantages:

Sterilization by means of heat requires

higher temperatures and longer exposures

than sterilization by steam. Heat transfer isslow, small volumes of oil and thin layers of

powder should be used.


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STERILIZATION

STEAM STERILIZATION:

Equipment: Autoclave

Method:

In the presence of moisture, microorganisms

are destroyed at a lower temperature than in

dry heat. This is the method of choice when

product can withstand such treatment.


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STERILIZATION

10 lb Pressure (115.5 deg. C)...30 minutes

15 lb Pressure (121.5 deg. C)...20 minutes

20 lb Pressure (126.5 deg. C)... 15 minutes


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STERILIZATION

Application:

1. Solutions sealed in containers ampuls, vials

2. Bulk Solutions

3. Glassware

4. Surgical Dressing

5. Instruments


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STERILIZATION

Advantages:

Rapid, Inexpensive, Effective, Large volumes

Disadvantages:

1. Cannot use for oily preparation (oil base

ointment)

2. Cannot use for moisture sensitive preparations


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STERILIZATION

FILTRATION:

Physical removal of microorganisms by

adsorption on the filter medium. Used for heatsensitive materials.


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STERILIZATION

BACTERIAL FILTRATION:

Equipment:

1. Porcelain filters

2. Siliceous earth filter

3. Sintered glass filters

4. Asbestos filters

5. Membrane filters


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STERILIZATION

Method: Direct filtration1. Positive pressure

2. Negative pressure

Application:

Thermolabile solutions of low viscosity.


1. Depend on filter media

2. Thermolabile solutions can be sterilized.


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STERILIZATION

GASEOUS STERILIZATIONEquipment:

Special oven, for admission of gas and

humidity & hermetic

Method:

Humidity of less than 20% RH

Ethylene Oxide


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STERILIZATION

Ethylene Oxide-Carbon dioxidePressure 30 psi

Temperature 20-55 deg. C

Application:

Thermolabile powder plastic\polymers

ophthalmic prep. subcutaneous, vaginal

inserts, plastic syringes, tubing sets


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STERILIZATION


1. Explosive hazard

2. Toxic

3. Not appropriate for solutions


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STERILIZATION

RADIATION STERILIZATIONEquipment:

Ultraviolet Lamp

Ionization (Beta Rays, Gamma Rays, X-Rays)Application:

Thermolabile Drugs (Powdered)


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STERILIZATION

Disadvantages:

1. Highly specialized equipment required

2. Effect of irradiation on products and their

containers.


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STERILIZATION

STERILITY TESTS (A) Microorganisms:

USPXXll recommends the use of biological

indicators.

1. For liquid preparations-add directly to the

preparations.

2. For solid preparations or equipments- add the

culture to strips of filter paper.


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STERILIZATION

Different organisms for different methods of

sterilization.

The organisms that are resistant to a particular

sterilization method should be chosen as themarker organism


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STERILIZATION

Sterilization Method Marker organisms

Steam sterilization Bacillus stearothermophyilus

Dry-heat sterilization Bacillus subtilis

Ethylene oxide Bacillus subtilissterilization

Ionizing radiation Bacillus pumilus

sterilization


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STERILIZATION

(B) Pyrogen and Pyrogen TestingPyrogens are fever producing organic

substances arising from microbial contamination.

The causative material is thought to be a

Lipopolysaccharide from the outer cell wall

of the bacteria.

This is Thermostable


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STERILIZATION

TESTS:

1. RABBIT TESTS

a) Render the syringes, needles and glassware

free from Pyrogens by heating at 250 deg. Cfor not less than 30 minutes.

b) Warm the product to be tested to 37 deg. 2

deg. C.c) Take three healthy rabbits


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STERILIZATION

d) Inject into an ear vein of each of three rabbits

10 ml of the product per kg body weight.

e) Record the temperature at 1,2,and 3 Hrs.


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STERILIZATION

CASE IResults:

(i) No rabbit shows an individual rise in temperature

at 0.6 deg. C or more above its respective control temp.

(ii) Sum of the three individual maximum temp. rises does

not exceed 1.4 deg. C.

Conclusion:

The material meets the USP requirements for the absenceof Pyrogen.


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STERILIZATION

CASE IIResults:

(i) If any rabbits show a temp. rise of 0.6 deg.C or

more or

(ii) If sum of the temp. rises exceeds 1.4 deg. C

Conclusion:

Repeat the tests using five other rabbits.


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STERILIZATION

Results:(i) If not more than three of the eight rabbits show

individual rises in temp. of 0.6 deg. C or more

(ii) If the sum of the eight temp. rises does not exceed 3.7

deg.C

Conclusion:

The material meets the USP requirements for the

absence of Pyrogens.


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STERILIZATION

2) LAL TESTS:

Limulus Amebocyte Lysate (LAL) Tests

Extract from the blood cells of the Horse

Shoe Crab (Limulus Polyphemus) containsan enzyme and protein that coagulates in the

presence of low levels of

Lipopolysaccharides.


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PARENTERAL DRUG

DELIVERY



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PARENTERALS

PARENTERALS

Injections:

These are sterile, Pyrogen free preparations

intended to be administered parenterally(outside alimentary tract).

Parental Routes Of Administration


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PARENTERALS

Most Common: 1. Subcutaneous (SC;SQ;SubQ)2. Intramuscular (IM)

3. Intravenous (IV)

Others: 4. Intracisternal5. Intradermal (ID)

6. Intraspinal

7. Intraarterial (IA)


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PARENTERALS

PARENTERAL ROUTE IS USED FOR:1) Rapid action

2) Oral route can not be used

3) Not effective except as injection


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PARENTERALS

Official Types of Injections:

1. Solutions of Medicinal

Example: Codeine Phosphate Injection

Insulin Injection

2. Dry solids or liquid concentrate does not contain

diluents etc.

Example: Sterile Ampicillin Sodium


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PARENTERALS

3. If diluents present, referred to as.....for injection

Example: Methicillin Sodium for injection

4. Suspensions

"Sterile....Suspension"

Example: Sterile Dexamethasone Acetate

Suspension


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PARENTERALS

5. Dry solids, which upon the addition of suitable

vehicles yield preparations containing in all

respects to the requirements for sterile

suspensions.Title: Sterile....for Suspension

Example: Sterile Ampicillin for Suspension


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PARENTERALS

Onset of Action\Duration

1. Chemical form of the drug

2. Physical state of the injection

(a) Solution

(b) Suspension

3. Vehicle used


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PARENTERALS

Most rapid onset of action:

Drugs that are very soluble in body fluids.

Drugs in aqueous solutions > Drugs in

oleaginous solution. Drugs in aqueous suspension > Drugs in

oleaginous suspension.

"Repository" or "Depot" Type injections - Longacting


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PARENTERALS

Requirements:

Solvents or vehicles used must meet special

purity and other standards.

Restrictions on buffers, stabilizers,antimicrobial preservative. Do not use

coloring agents.

Sterile and Pyrogen - Free.


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PARENTERALS

Must meet compendial standards for

particular matter.

Must be prepared under aseptic conditions. Specific and high quality packaging.


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A A S


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PARENTERALS

Restrictions on Fixed Oils:

Remain clear when cooled to 10 deg. C.

Not contain Paraffin or Mineral oil.

Must meet the requirement of iodinenumber and Saponification number.

PARENTERALS


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PARENTERALS

Iodine Number (Value):

It represents the number of g of iodine

absorbed, under the prescribed conditions, by

100g of the substance.

Saponification Value (Number):

It represents the number of mg of Potassium

Hydroxide required to neutralize the free acids

and saponify the esters contained in 1.0g of thesubstance.

PARENTERALS


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PARENTERALS

Must specify the oil used e.g. corn oil,cottonseed oil, peanut oil, sesame oil.

Must be free from rancidity.

PARENTERALS


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PARENTERALS

Solvents used must be:

Non-irritating

Non-toxic

Non-sensitizing

No pharmacological activity of its own

Not affect activity of medicinal

PARENTERALS


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PARENTERALS

Added Substances

-preservatives

-buffers

-antioxidants

-solubilizers

-thickeners

-materials to adjust tonicity

PARENTERALS


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PARENTERALS

Do Not Use Color

Preservatives: Multidose containers must

have preservatives unless prohibited by

monograph.

PARENTERALS


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PARENTERALS

ASEPTIC TECHNIQUE:

An aseptic technique is one which is

designed to prevent contamination of

materials, instruments, utensils, containers,during handling.

PARENTERALS


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PARENTERALS

Sources of Contamination

-The Air

-The Breath

-The Skin

-The Hair

-Clothing

-Working surfaces

PARENTERALS


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PARENTERALS

Methods of minimization of contamination:apply common sense

Airborne contamination--use laminar airflow

Horizontal Vertical

PARENTERALS


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PARENTERALS

HEPA filter

(High efficiency particulate air filter)

Contamination from the breath--use masks

Contamination from the skin:

Nails should be scrubbed

Hands and forearms should be washed

thoroughly with detergent solutions

PARENTERALS


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PARENTERALS

Hair and Clothing:

Always wear sterile gown over normal clothing

Long hair should be tied back

Wear a cotton cap

Working surfaces:

Clean the working surface with a bactericidal

solution or ethyl alcohol

PARENTERALS


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PARENTERALS

PACKAGING:1) Single dose: Hermetic container holding a quantity

of sterile drug intended for parenteral

administration as a single dose.

Example: ampuls sealed by fusion

2) Multiple dose: Hermetic container permits

withdrawal of successive portions of the contents

without changing the strength, quality, or purity of

the remaining portion.

PARENTERALS


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LABELING:Name of product

% of drug or amount of drug in specified volume

of amount of drug and volume of liquid to be

added

Manufacturer/Distributor

Lot number

Name and quantity of all added substances


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PARENTERALS


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AVAILABLE INJECTION:

Small volume parenterals (svp)

solutions Table 8-3

suspensions Ansel Pg 280Various insulin preparations

Table 8-5

Ansel Pg 282

PARENTERALS


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ONSET OF ACTION:Regular insulins > zinc suspension, prompt >

isophane suspension (NPH) >

zinc suspension *(lente) > protamine zincsuspension > zinc suspension, extended

PARENTERALS


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DURATION OF ACTION:

Regular insulin < zinc suspension, prompt

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