Glass ampuls and vials

• Glasses
• Forming processes

Ampuls and aluminum-seal vials are glass containers used primarily for packaging medication intended for injection. Ampuls are essentially single-dosage containers that are filled and hermetically sealed by flame-sealing the open end. Vials, which contain single or multiple doses, are hermetically sealed by means of a rubber closure held in place with a crimped aluminum ring.
An ampul is opened by breaking it at its smallest diameter, called the constriction. A controlled breaking characteristic is introduced by reproducibly scoring the glass in the constriction, or by placing a band of ceramic paint in the constriction. The ceramic paint has a thermal expansion that differs from the glass, thus, forming stress in the glass surface after being fired. This stress allows the glass to break in a controlled fashion at the band location when force is applied. Medication is then withdrawn by means of a syringe.
Medication can be withdrawn from a vial by inserting the cannula of a syringe through the rubber closure. Because the rubber reseals after cannula withdrawal, multiple doses can be withdrawn from a vial.
Both ampuls and vials are fabricated from glass tubing produced under exacting conditions. The glass used for these containers must protect the contained product from contamination before use and, in the case of light-sensitive products, from degradation caused by excessive exposure to light. In addition, the glass must not introduce contamination by interacting with the product.

GLASSES

The most important property of a glass used to contain a parenteral (injectable) drug is chemical durability; that is, the glass must be essentially inert with respect to the product, and contribute negligible amounts of its constituents to the product through long-term contact before use. The family of glasses that best meets chemical durability requirements is the borosilicates. These glasses also require higher temperatures for forming into shapes than other glass types.
When glass-product interactions are far less critical, the soda-lime family of glasses can be used to fabricate vials. These glasses can be formed at lower temperatures than borosilicates but do not nearly have their chemical durability. Typical compositions are shown in Table 1. Borosilicate and soda-lime glasses contain elements that facilitate refining, but borosilicates generally do not contain arsenic or antimony.
Both borosilicate and soda-lime glasses can be given a dark amber color by adding small amounts of coloring agents, which include iron, titanium, and manganese. The amber borosilicate and soda-lime glasses then can be used to package products that are light-sensitive.
The interior surface of containers formed from sodalime glass is often subjected to a treatment that enhances chemical durability without affecting the desirable lower melting and forming temperatures typical of soda-lime glass. For very critical applications, borosilicate ampuls and vials can be treated to improve their already excellent chemical durability.
For pharmaceutical packaging applications (see Pharmaceutical packaging), the various types of glass have been codified into groups according to their chemical durabilities, as specified by the United States Pharmacopeia (USP) (1). The glasses are classified by the amount of titratable alkali extracted into water from a crushed and sized glass sample during steam autoclaving at 2501F (121 1C). Thus, borosilicate glasses are typical of a USP Type I glass, and most soda-lime glasses are typical of a USP Type III glass. Some soda-lime glasses exist that are less chemically durable than Type III glass, and these glasses are classified as USP Type NP.
USP Type III (soda-lime) containers that have had their interior surface treated to improve durability can be classified as USP Type II if they meet the test requirements. The test in these cases is performed on the treated container instead of a crushed sample and uses a similar steam autoclave cycle.
The pharmacopeiae of other nations also have classified glass into groups according to their chemical durability. These classifications are generally similar to those specified by USP.

FORMING PROCESSES

Ampuls and vials are formed from glass tubing. The glass tubing is formed by processing in a glass furnace and by a tube-forming operation. The glass furnace operation consists of bulk batch preparation, continuous batch melting, and refining (see Glass-container manufacturing). The tube forming is done to exact specifications in either a Danner process or a downdraw process. The Danner process involves continuous streaming of molten glass onto an angled rotating sleeve that has an internal port for inflation air. The inflation air controls the tubing outside diameter (OD). The downdraw process is an extrusion process through an annular area. The inner core has an inflation air hole. The inflation air serves the same purpose as in the Danner process. In either process the tubing wall weight is controlled by adjusting the rate of glass withdrawal and supply. Typical ampul and vial tubing dimensions and tolerances are shown in Figures 1 and 2.






The tubing is formed in a continuous-line process. Various devices are used to support the tubing during pulling. A device, normally consisting of pulling wheels on belts and a cutting mechanism, is situated downstream to pull and cut the tubing. The tubing is cut to prescribed lengths and used in vertical- or horizontal-type machines for converting the tubing into vials or ampuls.
Many machines are rotary and either index or operate with a continuous action. The tubing is placed in the machines and is handled in a set of chucks. Heat is applied in the space between the chucks, and forming of the ampul or vial occurs throughout the machine rotation cycle.


Ampuls are formed on continuous-motion rotary machines. One sequence is shown in Figure 3. The process consists of sequentially heating and pulling (elongating the glass) to form the constriction, bulb, and stem contours of the ampul. The ampul contours are controlled primarily by proper temperature patterns in the tubing and by pulling rate of the tubing. Mechanical tooling of the glass can be used to assist in constriction contour forming. The forming process accurately controls the seal plane diameter, which controls ampul closing after filling. After the basic ampul is formed on the machine, the ampul blank is separated from the tubing and is transferred to a horizontal afterforming machine. On the afterforming machine the ampul is trimmed to length, glazed, and treated if necessary. Also, the ampul constriction can be either color banded with a ceramic-base paint or scored to control opening properties. The ceramic paint and scoring cause stress concentrations in the constriction, which assist in obtaining desirable opening force and fracture characteristics. Identification bands are applied and the ampul is annealed to relieve the strains caused by the thermal forming of the ampul. The completed ampuls are then transferred into a packing area where the ampuls are accumulated, inspected manually or automatically, and packed into clean trays for distribution (see Figure 4).


Vial forming is done on vertical machines that either index or have a continuous motion. A vertical forming sequence (see Figure 5) consists of a parting (separation operation), wherein a narrow band of glass is heated to a soft condition and the vial blank and the tubing are pulled apart. After parting, the finish-forming operations occur. The finish forming consists of heating and mechanically tooling the glass in sequential steps. Normally, multiple heating and tooling operations are necessary to form the closely held tolerances of aluminum-seal finishes. The tooling is done with an inner plug to control the contour and diameter of the finish bore and with outer contoured round dies that control the contour and diameter of the finish outer surface. The vial bottom contours are formed in the lower chucks whereas finish forming occurs for another vial in the upper chucks. After tooling, the vial length is set by a mechanical positioner. The process then continually repeats itself until the whole tubing length is consumed. After fabrication, the vial blank is transferred to a horizontal afterforming machine. The operations that are normally performed on an afterformer are dimensional gauging, vial treatment, and annealing. The vials are then transferred to a packing area where they are accumulated, inspected manually or automatically for cosmetic conditions, and packed in clean containers (see Figure 6).