TYPES OF GLASS USED FOR PHARMACEUTICAL PACKAGING There are four types of glass used in pharmaceutical containers.

The glass performance grades or Types used in pharmaceutical packaging are defined precisely in the USP as type I, type II, type III, and NP glass (1). Type I glass is borosilicate glass. Type II glass is very high-quality soda lime glass. The last two are lower grades of soda lime glass and approximate glass found in packaging food and other consumer products. Their performance characteristics are listed in the USP as type III glass and NP or nonparenteral glass. Both type III glass and NP glass are acceptable for food packaging. NP glass has a highest specification for leachable components in USPs standardized test. This difference makes its use and the development of testing to prove its suitability for a drug product more problematic. NP glass must be proven safe and acceptable for use in pharmaceutical packaging but really is closer to a general or generic grade of glass. It is one of the USP standards but not widely used in pharmaceutical packaging. Two limited applications for type NP glass are in packaging oral or topical products. It is not a material normally used in primary drug packaging.

USP Type I Glass USP type I (Table 2) glass is the most inert glass used for pharmaceutical packaging. It is borosilicate glass with approximate composition of 80% SiO2 and 10% B2O3. It still contains Al2O3 and sodium oxide (Na2O) in smaller amounts for the properties these materials impart to the finished glass. Borosilicate glass typically does not contain arsenic or antimony. Borosilicate glass has the lowest coefficient of thermal expansion and is the least likely to crack or break when subjected to sudden temperature changes. This provides durability and resistance to breakage during severe sterilization cycles required in manufacturing many pharmaceutical products. Type I glass is necessary for solutions that are slightly acidic. Acid solutions dissolve the various oxides in glass, causing a rise in the solutions pH. This change in pH may alter the efficacy of the drug, or it may change and reduce its shelf life or stability. Type I glass is the highest-defined or highest-specified quality level for glass used in the packaging of pharmaceutical products, and it is the most expensive. It has the lowest-specified limits for leachable materials defined by the USP. The glass is primarily used in ampules and vials for liquid parenteral products. USP type I glass is first converted into tubing and then into ampules, vials, and small volume bottles for pharmaceutical packaging. The conversion process is discussed in chapter 8, in the section describing glass container fabrication. The other types of glass (soda lime) use a more traditional method of manufacture. The use of USP type I glass in pharmaceutical packaging requires understanding of the need for its extremely high-performance characteristics. These characteristics cannot be obtained with other types of glass. The combination of inert chemical properties and impermeability are the two primary reasons for using this material. Other glass grades and other materials such as multilayer plastic materials cannot match these specific properties of borosilicate glass. When chosen as the glass material for a packaging application, the decision is based on chemical characteristics of the ingredient(s) in the drug product and the type of protection their chemistries require. Atmospheric oxygen protection and no interaction of the package with the API and carrier or diluents required by the active molecule make up the primary reasons for choosing type I glass. Real time and accelerated stability testing at ambient and elevated temperatures is used to confirm the high level of performance of the package with the drug. It provides a gas-impermeable inert environment inside the package needed for hard-to-hold, highly reactive drug products. USP Type II Glass Type II glass (Table 2), sometimes called soda lime glass, is the next grade or level of performance described in the USP. This glass does not contain boron and does not possess the properties of type I glass. This glass is sometimes referred to as treated soda lime glass or dealkalized soda lime glass. As would be expected from the type definitions in the USP, it is more resistant to leaching than type III glass, but less resistant than type I. The glass itself is made with the same ingredients and same processes as standard glass for packaging. The glass is made more resistant to leaching than normal soda lime glass by treating it with sulfur oxide (SO2). This process converts the surface oxides in the glass to soluble compounds that can be

washed away with warm or hot water and or dilute acid solutions. This glass after surface treatment is limited to one heat sterilization cycle and only one use as a package. The glass cannot be cleaned and autoclaved for reuse in dispensing liquid products. Repeated heat cycles will cause the soluble oxides to migrate or diffuse to the surface of the glass, negating the surface treatment. Type II glass is much easier to fabricate into bottles and other glass packaging because it has a lower melting point than borosilicate or type I glass. It is suitable for solutions that can be buffered to maintain pH below 7. The oxides in glass are labile, that is, free to move, as described and observed by their diffusion or blooming characteristics. These oxides are more easily leached by base solutions (pH > 7). Type II glass is seen as a lower-cost alternative to type I material. It can be fabricated at lower temperatures than type I glass, making manufacturing much easier. Bottle manufacture uses the same high-speed, high-volume equipment to make both food and pharmaceutical packaging. USP Type III Glass USP type III glass (Table 2) is untreated or standard soda lime glass. No surface treatment and no prerinse are used in its preparation prior to filling. Normally, Pharmaceutical Packaging Materials 197 this grade of glass material is used in pharmaceutical packaging for anhydrous liquids and dry products. The USP does specify the amount of leachable material permitted in their controlled test procedure, but the level is relatively high compared with type I and type II glasses. Depending on the nature of the product packaged, this type of glass can and is used for parenteral products following indications by testing that the product does not react with or leach out any of the glass contaminants. For larger volume containers, greater than 100 mL, this type of glass is suitable for use if testing determines that the amount of leachable interaction is low and acceptable to product stability. It is the lowest cost of the USP grades of glass. Type III glass is analogous with glass used in food packaging. Because it is used in applications with larger volumes of product, normally more than 100 mL, the high volume of product to surface area dilutes and limits the amount of leachable contamination to a low level. Type III glass provides a package cost standard for a pharmaceutical product equal to glass food and plastic containers. Nutraceuticals, the generic term used to describe a food product with enhanced characteristics that are not quite drugs, would consider this material as a starting point for packaging if plastics could not provide the product protection required. USP DESIGNATION NP GLASS The USP designates a lowest or minimum level of quality for glass that is called type NP or simply nonparenteral glass (Table 2). Again, the USP sets a limit for the amount of leachable oxide from the glass, but the limit is very high. This glass would typically contaminate small volume parenterals and make them unusable, but it is satisfactory for topical products like creams or lotions and for oral products like mouthwash. Normally, the volume of product packed in NP glass exceeds 100 mL.

GLASS AS A PHARMACEUTICAL PACKAGING MATERIAL Glass has advantages and disadvantages associated with its choice as a pharmaceuticalpackaging material. Probably, the two best characteristics of glass are its resistance to chemical attack by almost all liquids except hydrofluoric acid (HF) and strong caustics along with its impermeability. Glass being impermeable prevents any volatile ingredients from escaping and prevents any environmental gases, primarily oxygen, from entering the container. Glass disadvantages include its brittleness and weight. Glass brittleness is a problem that translates into glass breakage and the tendency of glass to break into numerous fragments. Even when care is taken to prepare glass to break by scoring or other techniques that thins the glass, in a container designed to be broken such as an ampule, the glass can shatter into fine fragments that may be ingested with the drug. Glass has a high density (22.5 g/cc), which in combination with its brittle nature means that containers must be fabricated with thick walls to achieve adequate durability. The thick walls make the resulting product heavy and increase transportation costs. This is a disadvantage compared with plastic and metal containers. A short list of the advantages and disadvantages of glass as a package is as follows: Advantages 1. Compression strength (permits stacking in distribution) 2. Material strength to permit hot filling and retorting 3. Heat resistance (can be autoclaved and sterilized with heat treatments) 4. Impermeable to gases 5. Inert (most inert material of all drug packaging materials) 6. Clarity (contents easily viewed without opening) 7. Easily cleaned and sterilized 8. Fabricated into multiple sizes and shapes 9. Technology for filling, sealing, and labeling is mature. 10. Consumers everywhere are familiar with the package. 11. Widespread availability (except type I glass) Disadvantages 1. High densityhigh weight (high transportation costs)

2. Brittlenesseasily breakable (broken glass can contaminate ampule products designed to break) 3. Slower and more costly to fabricate than metal or plastic