Containers and Closers for Parenteral Sterile Preparation/Product

  • Parenteral/injectable preparations are packaged into containers made of glass or plastic.
  • Container systems include or Various type of parenteral containers:-
    • Ampoules
    • Vials
    • Syringes
    • Cartridges
    • Bottles
    • Bags
Container for Parenteral Products
Containers for parenteral Preparation

Glass container

  • Glass is composed of Silicon dioxide & a varying amount of oxides Na, K, Ca, Mg, Al, Boron etc.
  • Basic structure network silicon dioxide tetrahedron.
  • Baric oxide easily enters into the network structure of silicon dioxide & bound tightly & does not leach into the solution of the container. But other oxides do not enter into the network structure of silicon dioxide & loosely bound (other oxides), hence Relatively free to migrate which result in leached into solution in the glass Container, especially during the thermal Sterilization process.  The leached oxide may hydrolyze & finally result in Raise pH & may catalyze or enter into the undesired reaction.

Glass containers are classified on the basis of hydrolytic resistance

  1. Type I/Borosillicate
  2. Type II/Sodalime treated 
  3. Type III/Sodalime glass
  4. Type IV/NP

Type I/Borosillicate

  • Also, know as Neutral Glass
  • Composition – 81% – silicon dioxide; 13% – Boric oxide; other oxide (Na & Al etc) – non network forming oxide.
  • Type Glass – Chemically inert – glass have high hydrolytic resistance due to the presence of Boric oxide & a high melting point due to silicon dioxide.
  • Used for all types of preparation whether parenteral preparation or not & for all acid & Alkaline preparation or whether buffered or not.

Type II/Sodalime treated glass

  • Composed of silicon dioxide & high proportional of Sodium oxide ( 14%) & Calcium oxide ( 18%).
  • Also high hydrolytic resistance.
  • Treated with SO2 & other dealkalizers to neutralize interior surface of the container [under controlled temp & humidity] to increases chemically resistance of glass.
  • Also known as Sodalime treated glass
  • Used for Acidic & Neutral or pH<7 buffered preparation

Type III/Sodalime glass

  • moderate hydrolytic resistance
  • Used for Non Aqueous Parenteral & powdered for injection preparation.

Type IV/NP glass

  • Not used for parenteral preparation.
  • Used for Oral use dosage form.

Container of Type-II & Type-III glass should be used once only

Siliconization: The application of a thin film of silicone to coat the inside surface of the vials and ampoules has been employed to prevent interaction of the product with the glass surface. The process also minimizes adsorption of active ingredients from homogeneous solutions, prevents adsorption of solids from suspensions and prevents aggregation at the glass surface in colloidal preparations.

Powdered Glass Test & Water Attack Test

Types of Glass is determined from two tests:-

  1. Powdered Glass Test
  2. Water Attack Test
Powdered Glass TestWater Attack Test
Applicable to Glass Type I, III, & IV Applicable to Glass Type II only
Challenge leaching potential of inner/interior surface of a glass containerChallenge only intact surface of a glass container
Performed on a part of the containerPerformed on the whole container
Powdered Glass Test & Water Attack Test for glass container

Hydrolytic resistance test for Glass container

Type of container Test to be done
Type I and II to distinguish from Type IIIType I (surface test)
Type I and Type II have high hydrolytic resistance is due to chemical or treatmentA test I and II both
Hydrolytic resistance test for Glass container

Plastics containers

For sterile preparations, such as large-volume parenterals, ophthalmic solutions, and, increasingly, small- volume parenterals, Thermoplastic polymers have beenused as packaging materials.

Plastics used in the packaging of parenteral products are based on polyethylene or polypropylene. Only polypropylene containers can withstand sterilization by autoclaving.

Advantages of using plastic packaging materials

  • they are not breakable, as is glass.
  • less weight as compare to glass so less transport cost
  • flexiblility: bags of polyvinyl chloride or select polyolefins.

Disavantages of using plastic packaging materials

  • not being as clear as glass
  • soften or melt under the conditions of thermal sterilization

There are three major problems occurs in using plastic materials:

  1. Permeation of vapors and other molecules in either direction through the wall of the plastic container
  2. Leaching of constituents from the plastic into the product
  3. Sorption (absorption and/or adsorption) of drug molecules or ions on the plastic material.

Closures for Parenteral Preparation: Rubber

Closures (Pharmaceutical closures, also known as stoppers or bungs) that form part of the container-closure system. Container-closure system are an important component in the packaging of sterile products.

Container-closures maintain the sterility of parenteral pharmaceuticals and prevent contamination when a needle is inserted into a vial.

The most commonly used type of stopper is the elastomeric closure/Rubber closure.

The elastomer is either natural rubber or synthetic rubber, such as butyl rubber or chlorobutyl rubber. The advantage of synthetic rubbers is that the materials are strongly resistant to permeation by oxygen or to water vapor.

Also, Read…

Glass container

  • Glass is composed of Silicon dioxide & a varying amount of oxides Na, K, Ca, Mg, Al, Boron etc.
  • Basic structure network silicon dioxide tetrahedron.
  • Baric oxide easily enters into the network structure of silicon dioxide & bound tightly & does not leach into the solution of the container. But other oxides do not enter into the network structure of silicon dioxide & loosely bound (other oxides), hence Relatively free to migrate which result in leached into solution in the glass Container, especially during the thermal Sterilization process.  The leached oxide may hydrolyze & finally result in Raise pH & may catalyze or enter into the undesired reaction.

Glass containers are classified on the basis of hydrolytic resistance

  1. Type I/Borosillicate
  2. Type II/Sodalime treated 
  3. Type III/Sodalime glass
  4. Type IV/NP

Type I/Borosillicate

  • Also, know as Neutral Glass
  • Composition – 81% – silicon dioxide; 13% – Boric oxide; other oxide (Na & Al etc) – non network forming oxide.
  • Type Glass – Chemically inert – glass have high hydrolytic resistance due to the presence of Boric oxide & a high melting point due to silicon dioxide.
  • Used for all types of preparation whether parenteral preparation or not & for all acid & Alkaline preparation or whether buffered or not.

Type II/Sodalime treated glass

  • Composed of silicon dioxide & high proportional of Sodium oxide ( 14%) & Calcium oxide ( 18%).
  • Also high hydrolytic resistance.
  • Treated with SO2 & other dealkalizers to neutralize interior surface of the container [under controlled temp & humidity] to increases chemically resistance of glass.
  • Also known as Sodalime treated glass
  • Used for Acidic & Neutral or pH<7 buffered preparation

Type III/Sodalime glass

  • moderate hydrolytic resistance
  • Used for Non Aqueous Parenteral & powdered for injection preparation.

Type IV/NP glass

  • Not used for parenteral preparation.
  • Used for Oral use dosage form.

Container of Type-II & Type-III glass should be used once only

Siliconization: The application of a thin film of silicone to coat the inside surface of the vials and ampoules has been employed to prevent interaction of the product with the glass surface. The process also minimizes adsorption of active ingredients from homogeneous solutions, prevents adsorption of solids from suspensions and prevents aggregation at the glass surface in colloidal preparations.

Powdered Glass Test & Water Attack Test

Types of Glass is determined from two tests:-

  1. Powdered Glass Test
  2. Water Attack Test
Powdered Glass TestWater Attack Test
Applicable to Glass Type I, III, & IV Applicable to Glass Type II only
Challenge leaching potential of inner/interior surface of a glass containerChallenge only intact surface of a glass container
Performed on a part of the containerPerformed on the whole container
Powdered Glass Test & Water Attack Test for glass container

Hydrolytic resistance test for Glass container

Type of container Test to be done
Type I and II to distinguish from Type IIIType I (surface test)
Type I and Type II have high hydrolytic resistance is due to chemical or treatmentA test I and II both
Hydrolytic resistance test for Glass container

Plastics containers

For sterile preparations, such as large-volume parenterals, ophthalmic solutions, and, increasingly, small- volume parenterals, Thermoplastic polymers have beenused as packaging materials.

Plastics used in the packaging of parenteral products are based on polyethylene or polypropylene. Only polypropylene containers can withstand sterilization by autoclaving.

Advantages of using plastic packaging materials

  • they are not breakable, as is glass.
  • less weight as compare to glass so less transport cost
  • flexiblility: bags of polyvinyl chloride or select polyolefins.

Disavantages of using plastic packaging materials

  • not being as clear as glass
  • soften or melt under the conditions of thermal sterilization

There are three major problems occurs in using plastic materials:

  1. Permeation of vapors and other molecules in either direction through the wall of the plastic container
  2. Leaching of constituents from the plastic into the product
  3. Sorption (absorption and/or adsorption) of drug molecules or ions on the plastic material.

Closures for Parenteral Preparation: Rubber

Closures (Pharmaceutical closures, also known as stoppers or bungs) that form part of the container-closure system. Container-closure system are an important component in the packaging of sterile products.

Container-closures maintain the sterility of parenteral pharmaceuticals and prevent contamination when a needle is inserted into a vial.

The most commonly used type of stopper is the elastomeric closure/Rubber closure.

The elastomer is either natural rubber or synthetic rubber, such as butyl rubber or chlorobutyl rubber. The advantage of synthetic rubbers is that the materials are strongly resistant to permeation by oxygen or to water vapor.

Also, Read…


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