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Containers and Closures

  • Container is that which holds the article and is or may be in direct contact with the article.
  • Closure is part of container and is most vulnerable and critical component of container. It must be effective in preventing any escape from the container and allow no substance to enter the container.



Main Requirement
Should not interact physically or chemically with the article placed in it, so as to alter the strength, quality or purity of the article beyond the official requirements.

Types of Containers

Tamper Resistant Packaging:
For ophthalmic/otic use. It shall be so sealed that the contents cannot be used with out obvious destruction of seal.

Light Resistant Container:
Protects contents from effects of light.


Well closed container:
Protects contents from extraneous solids & from loss of article under ordinary/ customary conditions of handling, shipment, storage & distribution.

Tight Container:
Protects contents from contamination by extraneous liquids, solids / vapours and also protects from loss of article from efflorescence or evaporation.

Hermetic containers:
Impervious to air / any other gas.

Single unit container:
It holds a quantity of drug product for administration as a single dose or a single finished device intended for use promptly after the container is opened.

Single dose container:
Intended for parenteral administration in general

Multiple unit container:
Without changing the strength, quality or purity of remaining portions.

Multiple dose container: 
for parenterals.

Different Storage Temperatures:

Freezing: Maintained thermostatically between - 25 to –10 ℃.
Cold: Between 2 to 8 
Cool: Between 80 to 15 0C (460 to 59 0F)

Room Temperatures:
Temperature prevailing in working area 20 to 25

Controlled room temperature:
15 to 30 (Label: “Controlled room temperature” / “ Upto 25 ”)

Warm:
Temperature between 30 to 40 

Excessive heat:
Temperature above 40 

Storage under non specific conditions:
Conditions include protection from moisture, freezing and excessive heat.


Different types of Containers
  1. GLASS
  2. PLASTIC
1. GLASS CONTAINERS
Composition of Glass:
  • Sand: Pure silica
  • Soda ash: Sodium carbonate
  • Lime stone: Calcium Carbonate
  • Cullet: broken glass acts as fusion agent

  1. Common Cations found in pharmaceutical glass ware are Si, Al, Bo, Na, K, Ca, Mg, Zn, Ba.
  2. Main Anion is Oxygen

Uses of Cations:
  1. Sodium – Chemically Resistant
  2. Boron Oxide - aids in melting process to reduce temp.
  3. Lead - gives clarity and brilliance
  4. Alluminium oxide - increases hardness & Durability and also Resistance to chemical action.

Different grades of Glass

Type

Description

Test

LIMITS

Used in

Size (ml)

ml of 0.02N acid

 

I

Highly resistant borosilicate glass

Powdered glass

All

1.0

Parenterals

II

Treated soda lime Glass

Water attack

100 or less

Above 100

0.7

0.2

 

III

Soda Lime Glass

Powdered glass

all

8.5

With exception

NP

GP       Soda lime Glass

Powdered glass

all

15.0

Oral    & topical



2. PLASTIC CONTAINERS
  • Polyethylene
  • Poly propylene
  • Poly vinyl chloride
  • Polystyrene


Containers are usually made from one or more polymers with additives viz., Antioxid, Antistatic agents, Colors, Impact modifiers, Lubricants, Plasticizers, Stabilizers

Problems encountered with Drug-Plastic containers:

Permeation, Leaching, Sorption, Chemical reaction, Modification

TESTS:
  • LIGHT TRANSMISSION TEST: Containers intended to provide protection from light.
  • CHEMICAL RESISTANCE: Containers composed of glass. 
  1. Powdered glass test
  2. Water attack at 121 0C
  3. Arsenic test.
  • Containers composed of plastic & intended for packaging parenteral products
  1. BIOLOGICAL TESTS
  2. PHYSICO CHEMICAL TESTS

Light Transmission Test:
Measure light transmittance with reference to air 290 to 450nm

Chemical Resistance:
  • Measure of resistance to water attack i.e., the amount of alkali released from the glass under the influence of the attacking medium.
  • More resistant Glass – Less release of Alkali

Powdered Glass Test:
Crushed material retained on 50 mesh, take 10g in 250ml conical flask, Add 50ml of HPW. Place in autoclave, Heat till steam releases & hold for 10 min, Set temp. at 121 ℃ (+ 0.2 ) for 30 min, Cool at once in running water. Decant and wash the portions with water and collect. Take 15ml in a conial flask + 5 drops methyl red sol. Titrate with 0.02N H2SO4

Water attack Test:
3 or more containers, Fill 90% with HPW, (Continue as in Powdered glass test), Holding Time is 60 min.Take 100ml of solution for testing, (Continue as in Powdered glass test),

Permeation:
12 containers, fill with dessicant, record weights, Store at RH 75 + 3%, Temp 20 (+ 2 ) 14 days, record weights every day.

Moisture permeation:
5 containers, fill with water, record weights, transfer water contents & measure volume.

Limits: 
10 – NMT 2000mg/ day weight gain, Should not exceed 3000mg /day are considered as Well closed containers

Tests on Plastics:

1. Biological Tests: 
Where extractions obtained from samples are injected to test animals for possible reaction.

In Vitro: Agar Diffusion Test, Direct Contact Test, Elution Test (Mammalian Cell Culture)
In Vivo: Systemic injection Test, Implantation Test, Intracutaneous Test, Eye Irritation Test
Safety Tests – for unacceptable, unexpected, biological reactivities.


2. Physico chemical Tests:

With Extracted Solution: 
  1. Non Volatile Residue
  2. Residue on Ignition
  3. Heavy Metals
  4. Buffering Capacity


CLOSURES

Different Types of closures : 5 designs
  1. Screw on, threaded or Log
  2. Crimp on (Crowns)
  3. Press on (Snap)
  4. Roll on
  5. Friction

In variation to the basic types :
  1. Vacuum
  2. Tamper PRoff
  3. Safety
  4. Child Resistant
  5. Linerless types
  6. Dispenser Applications

THREADED SCREW CAPS:
The threads engage with the corresponding threads molded on the neck of the bottle.
Liner of the cap, gets pressed against the opening of the container, seals the product in the container.

LUG CAPS:
Same principle as above, but a simply interrupted thread on the glass finish. It requires a quarter turn to close or open.

CROWN CAPS: 
Crimped closure for beverage bottles.

ROLL ON CLOSURES:
Straight sided, thread less which forms the threads on the packaging line, can be securely sealed and opened and resealed again.

Other types include:
  • Resealable / Reusable Closures
  • Pilfer Proof Closures:

Similar to roll on closures but with greater skirt length.

Additional length extends below the threaded portion to form a bank, which is fastened to the basic cap by series of narrow metal “Bridges”.
  • Non Resealable / Non Reusable Closures: They require unthreaded glass finishes.

The skirts of these closures are rolled under retaining rings on the glass container and maintain liner compression. They have tear off tabs that make them tamper proof and Pilfer proof.


Closure Liners:
Any material that is inserted in a cap to effect a seal b/n closure and container. It is glued into the cap / the cap is made with an under cut to facilitate the liner and so easily rotates.
  • Made of resilient backing and a facing material.
  • The backing material should be soft and elastic enough.

Factors in selecting a liner: Chemically inert.

Types of liners:
Homogenous Liner
  • One piece liners available either as disk or ring of rubber or plastic.
  • Properties are uniform and can withstand high temperature sterilization.
  • Widely used in pharmaceuticals.
  • More expensive and more complicated to apply.

Heterogenous or Composite Liners:
Composed of 2 layers 
  1. Facing – with the product
  2. Backing – for cushion with cap

TORQUE TESTING:
Owens – Illinois Torque Tester.
Controlling Cap Tightness
With Torque Tester.
Prevents evaporation or leakage of material

Rubber Stoppers:
  • Primarily used for multiple dose vial, Disposable syringes.
  • Different Rubber Polymers used are:
  1. Natural 
  2. Neoprene 
  3. Butyl rubber

Different ingredients in rubber closures are:
  1. Rubber, 
  2. Vulcanizing agent, 
  3. Accelerator / activator
  4. Extended filler, 
  5. Reinforced filler, 
  6. Softener / Plasticizer
  7. Antioxidant, 
  8. Pigment, 
  9. Special Components - Waxes

Plastic Closures:
Two Types: 
  1. Thermosetting Resins.
  2. Thermoplastic Resins

Thermosetting Closures:
  • Widely used, made of Thermosetting phenolic and urea plastic resins.
  • Usually fabricated by compression molding.
  • Plastic first softens under heat and then cures and hardens to a final state.

Thermoplastic Closures:
Polysterene, 
Polyethylene, 
Polypropylene


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