Containers and Closures

The container is that which holds the article and is or may be in direct contact with the article.

The closure is part of the container and is the most vulnerable and critical component of the 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 without obvious destruction of the seal.

Light Resistant Container:

Protects contents from the 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/vapors 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 number of drug products 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 the remaining portions.

Multiple dose container: 

for parenteral.

Different Storage Temperatures:

Freezing: Maintained thermostatically between - 25 to –10 ℃.

Cold: Between 2 to 8 ℃

Cool: Between 80 to 15 ℃ (460 to 59 ℃)

Room Temperatures:

Temperature prevailing in the working area is 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
• Limestone: Calcium Carbonate
• Cullet: broken glass acts as a fusion agent

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

Uses of Cations:

1. Sodium – Chemically Resistant
2. Boron Oxide - aids in the melting process to reduce temp.
3. Lead - gives clarity and brilliance
4. Aluminum 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
• Polypropylene
• Polyvinyl 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. PHYSICOCHEMICAL TESTS

Light Transmission Test:

Measure light transmittance with reference to air 290 to 450nm

Chemical Resistance:

• The 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 an 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 conical 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 desiccant, 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 a 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.

ALSO READ: Pre-formulation and Formulation Development

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 proof
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.

The liner of the cap gets pressed against the opening of the container and 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:

The straight-sided, thread 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 a 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 undercut to facilitate the liner and so easily rotates.

• Made of resilient backing and 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 are available either as a 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 vials and 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:

Polystyrene, 

Polyethylene, 

Polypropylene

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