Cleaning and sterilization of containers

and closures

• Utpal Kumar Saha

• M. Pharm (DU)
 Aseptic pharmaceutical manufacturing
• Clean room, validation of clean room
• HVAC system
• Cleaning and sterilization of containers and closures
• Pyrogen and depyrogenation.
• Filling and sealing of sterile products.
• Clean in place (CIP) and sterilize in place (SIP) system.
• Manufacturing of SVP and LVP
Cleaning and sterilization of containers and
closures
Containers –
• refers to storage media in which product is placed & enclosed & it is in
direct contact with the drug. ( glass, plastic)
• Pharmaceutical container - is a device that hold the pharmaceutical
product and it may or may not be in direct contact with Product.
Closures –
• tightly pack the container to exclude O2, co2, moisture.
• prevent loss of water & volatile substance from the product during
transport & handling.
• part of container system
• may or may not be in direct contact with Product. (Aluminum, rubber)
Cleaning and sterilization of containers and
closures
Small Volume Parenteral Product Containers (volume up to 100 ml)
• Single dose containers:-ampoule (glass/plastic) , vials
• Multi dose containers: vials (glass)
• Prefilled Syringe
• For LVP, type 2 glass is used but type 1 can also be used for the products having high
pH.
Large Volume Parenteral Product Containers
• Glass Bottles
• PVC Collapsible Bags
• Semi rigid Polythene Containers
Dropper Bottles
• Eye drop and dropper bottles for ear and nasal use are amber color glass containers
• Fitted with cap, rubber teat and dropper as the closure.
Cleaning and sterilization of containers and
closures
GLASS–
o Ampoules, Vials, Bottles etc.
o Complies with hydrolytic resistance.
o There are 3 types of glass used
o resistance to water attack of new glass containers
o the degree of attack being determined by amount of alkali released from the glass
under specified conditions.
• Type-I (Neutral glass) – It has a high hydrolytic resistance due to chemical composition
of glass. It is also called borosilicate glass.
• Type-II (treated soda lime glass) – It has a high hydrolytic resistance due to an
appropriate surface treatment.
• Type-III (regular soda lime glass)- moderate hydrolytic resistance ,used only for non-
aqueous liquid preparations or for powders for injection.
• NP – General purpose, Not for Parenteral soda lime glass
Cleaning and sterilization of containers and
closures
PLASTIC CONTAINER:
• Thermoplastic polymer.
• Polyethylene and Polypropylene are the most commonly used polymer.
• Others: Poly Vinyl Chloride ,Polystyrene, Polymethyl Methacrylate ,Poly
Carbonates
• Formulated with low amount of plasticizers.
• Must be autoclaved.
• Plastic containers are used mainly because of
- light in weight
- non breakable
- low toxicity
- low reactivity with products.
Cleaning and sterilization of containers and
closures
PLASTIC CONTAINER:
• The USP has provided test procedures for evaluating toxicity of plastic
materials.
• Packaging of large volume parenterals like saline bags.
Polyethylene
• Its is flexible, very light but tough plastic
• It is impermeable to water vapour and does not deteriorate with age
unless it is exposed to sunlight for long time
• It has permeability to certain oils and preservatives.
Cleaning and sterilization of containers and
closures
PLASTIC CONTAINER:
Polyethylene
• Its melting point being in the range of 110 ° C to 150 ° C
• It has high melting point and can sterilized by autoclaving.
• It is divided into
• HDPE (HIGH DENSITY POLYETHYLENE ) : -Rigid, withstand temperature
up to 120 ° C
• LDPE ( LOW DENSITY POLYETHYLENE ) :-Flexible, withstand temperature
up to 80 ° C
Cleaning and sterilization of containers and
closures
PLASTIC CONTAINER :
 Polyvinyl Chloride (PVC)
• It is less flexible , heavier and more permeable to water vapors as
compared with normal polythene .
• It has high clarity and not effected by sunlight.
• It is used for preparing eye ointment tubes .
• Flexible PVC is main component for intravenous bags.
Polystyrene
• It is a hard, rigid , light material
• It can be easily molded into any shape
• So it is used for preparing bottles, tubes ,jars for ointments and
cream ,boxes and syringes.
 Cleaning and sterilization of containers and
closures
PLASTIC CONTAINER :
 Polymethyl Methacrylate (PMMA)
• It is hard , strong but light, transparent plastic
• It is used for preparing bottles and tubes.
Polycarbonate
• It is transparent, has high impact strength and very good heat
resistance.
• It is used in the preparation of surgical equipment.
• It has been used in blood oxygenators, blood reservoirs, and blood
filters used in the bypass circuit for more than 20 years.
Cleaning and sterilization of containers and
closures
RUBBER CLOSURES:
• Rubber is used in manufacture of closures, caps, vials wrappers and plungers
• Influence preservative loss from solution and antimicrobial activity
respectively.
Composition of Rubber Closure: It is made up of
1. natural rubber (latex) & or a synthetic polymer,
2. a vulcanising agent (sulfur),
3. an accelerator (2-mercaptobenzothiazole),
4. an activator (Zno),
5. filler (carbon black/limestone) and
6. other ingredients such as antioxidants & lubricants.
Compatibility of rubber closures with the drug
Cleaning and sterilization of containers and
closures
Type of Cleaning
 Air- jet Cleaning : Air is passed through inverted bottle & suction of
particle
 Cleaning with water & air (Plastic/PET Bottle)
Cleaning Procedure
 Manual washing
 Semi- Automatic washing
 Automatic washing
Principle: Water & air spray or inject into the inverted bottle/container &
outer surface as per required cycle
 Automatic washing with Sterilization tunnel
Cleaning and sterilization of containers and
closures
Manual washing
Semi- Automatic washing
Automatic washing
Automatic washing with
Sterilization tunnel
Cleaning and sterilization of containers and
closures
Sterilization Procedure
 Sterilization by dryheat- A minimum of 180° C for not less than 30
minutes or 160° C for not less than 2 hrs- Vial, Ampoule.
 Sterilization by bacteriostatic agents -100ºC for 30 minutes. Chlorocresol
0.2%(w/v), Phenyl mercuric nitrate (PMN) 0.002%, - must be compatible
with the product. i)Injection fluid ii)Eye drops .
 Sterilization by moist heat –Temp.:121° C, Time : 15 minutes, Pressure: 15
lb/square inch (psi) – Autoclave -Rubber stopper, Closure.
 Sterilization by radiation- infrared, ultraviolet, gamma radiation and high
velocity electrons – Ointment tube, plastic syringes, catheters, plastic
tubes in saline sets etc.
 Sterilization by gases and fumigants- ethylene oxide, formaldehyde-
Disposable syringes, needles.