The U.S. Pharmacopeia classifies pharmaceutical glass containers according to their chemical durability, which is their resistance to water attack. Different types of glass react differently when exposed to solutions and vapors. Reactive substances will leach constituents from the glass surface into the contained product. This reaction can occur with ordinary aqueous, saline and alcohol based solutions. The primary ion removed from the glass surface is sodium; however all elements are subject to leaching. It is not uncommon to experience an increase in product pH as sodium is extracted from the container. Corrosion of the glass occurs over time and is accelerated by moist heat- treating processes like autoclaving.
Containers are classified by the USP as Type l, Type II and Type lll. Type I is the most chemically durable glass and Type III is the least durable. Test methods and specification limits are determined by the USP in Chapter Containers. USP Type can be used as a general guide for container selection but should not be the only criteria in the decision making process. A set of criteria has been developed over the years to assist with the selection of glass containers. These guidelines were established to narrow the selection of possible containers. It is the product manufacturers responsibility to do testing to ensure that the glass container is suitable for the application and contained product.
USP Type I
USP Type I classification is a borosilicate glass with superior chemical resistance. This class of glass represents the least reactive glass containers available. Typically, this glass can be used for most applications, including packaging for parenteral and non-parenteral products. Type I glass may be used to package acidic, neutral and alkaline products. Water for injection, unbuffered products, chemicals, sensitive lab samples and those requiring sterilization are commonly packaged in Type I borosilicate glass. Type I glass can be subject to chemical attack under certain conditions, thus container selection must be made carefully for very low and very high pH applications. Most glass laboratory apparatus are Type I borosilicate glass.
Even though Type I glass has the highest chemical durability, there still may be some sensitivity with certain packaged products. For applications where standard Type I glass does not provide sufficient protection against alkali extraction and pH shifting, internal surface treatment can be used to further improve the chemical durability of the container. This surface enhancement may become especially important for pH sensitive products packaged in small containers because smaller containers have a higher surface area to volume ratio. See the USP Type II description for an explanation of the internal surface treatment process. It should be noted that the USP does not place any additional durability requirements on surface treated Type I glass.
USP Type II
USP Type II glass is soda-lime glass that has been treated with sulfur compounds to de-alkalize the interior surface of the container. This treatment results in a container with high chemical resistance because alkali is removed from the glass surface prior to use. The amount of ions available to leach into the product is reduced, thus the container durability is increased. Extraction salts will be present on the interior surface of new sulfur treated containers, and the containers may require washing prior to use. Type II glass is less chemically durable than Type I glass, but is more chemically durable than Type III glass. It can be used for acidic and neutral parenteral preparations that remain below pH 7 during their shelf life.
USP Type III
Type III glass may not be suitable for autoclaved products because the autoclaving process will accelerate the glass corrosion reaction. Dry heat sterilization processes are typically not a problem for Type III containers.
Factors other than USP Type
It is important to consider filling and processing steps when choosing a container. Both mechanical and thermal stresses are important factors. For a given thermal expansion range, a typical tubing vial with thin, uniform walls will withstand thermal shock better than a molded glass container.
The physical design of the container will play a part in the amount of thermal and mechanical shock resistance it exhibits. It is often necessary to make a compromise between high resistance to mechanical shock and high resistance to thermal shock.
Light sensitive products must be packaged in amber glass. Amber glass is formulated to absorb light in the Ultra Violet region of the electromagnetic spectrum. Test methods and specification limits for light protection can be found in the U. S. Pharmacopoeia.
Specific Ion Sensitivity
If a product is sensitive to the presence of particular ions, the composition of the glass container should be considered. For example, products that contain sulfate salts may experience the formation of precipitates if packaged in glass with barium or calcium in the formulation. In this example, it would be desirable to avoid glass that contains barium and calcium. A second example is pre-cleaned containers for environmental sampling. Even though the containers are clean, the chemical durability characteristics of the glass have not been altered. Thus, it would not be feasible to test the samples for low levels of sodium, because the sample will extract sodium from the container’s surface.