Pharma glass defects - 1. Residual stress

Hello everyone – I posted an article last week providing a general introduction to pharma glass quality and defects.  I also mentioned at the end of that post that I would start considering Critical defects in more detail.  Before getting into today’s specific topic, I need to set the stage by mentioning that the latest revision of PDA Technical Report 43 (Identification and Classification of Nonconformities in Moulded and Tubular Glass Containers for Pharmaceutical Manufacturing) was published in late 2023 (see Footnote 1). This reference document is an important foundation for quality standards that define acceptable levels for various Critical, Major, and Minor defects in parenteral glass containers of all types. There are a number of important updates from the prior revision that was released in 2013 – the topic of today’s post is a great example. The 2023 revision of TR 43 has removed “Residual Stress” from the official lexicon for visual defects. However, residual stress can be an important precursor to visual defects that are included in TR 43 such as cracks and various forms of breakage.

The topic of residual stress came up briefly in a prior post on glass viscosity.  I mentioned how temperatures within the range of the annealing point and strain point can be used to help define an annealing process used to remove residual stress from a glass container. However, I didn’t really discuss the source of this residual stress, and so let’s start there. Figure 1 is an example of a Volume-Temperature (V-T) diagram of a material that can be formed into a glass or a crystalline solid. Using this one diagram as a springboard, I could literally spend a few days talking about various glass-related topics. In the interest of brevity let’s just focus on a couple key points.

Point #1 – there is the difference in behavior between a glass and a crystalline solid. Consider a case in which a liquid is being cooled towards the crystallization temperature. The crystallization event is accompanied by an instantaneous change in volume. This change from a liquid to a crystalline solid often (but not always) results in a volume decrease. Depending on the composition of the liquid, there can be an increased propensity for supercooling to occur – i.e., the liquid cools below the crystallization temperature without transforming into a crystalline solid (see Footnote 2). Note that that there is no discontinuous change in volume when moving from the liquid to the supercooled liquid. As cooling continues, the viscosity of the supercooled liquid continues to increase to a point where rearrangement of the structure is no longer possible in a relatively short period of time. We enter the so-called “transformation range” where the supercooled liquid becomes a glass (see Footnote 3). Notice that the glassy state has a higher volume than the corresponding crystalline solid. This has interesting implications for a number of properties, including density and refractive index.

Point #2 – the rate of cooling through the transformation range matters. Faster cooling causes a more rapid increase in viscosity, which in turn dictates when the V-T curve begins to diverge from the supercooled liquid line. By extension, faster cooling will also generally produce a glass that is higher in volume relative to a slow-cooled glass. This brings us to the main topic of today’s post. The process of making a pharmaceutical glass container inevitably involves a process of heating and cooling. For example, imagine the freshly formed flange of a glass vial. The exterior surfaces of the flange will tend to cool at a faster rate than the glass within the interior of the flange. This differential cooling rate leads to the development of residual tensile and compressive stresses within the glass container, and the magnitude of these tensile stresses can be high enough to cause mechanical failure. Fortunately, the removal of forming-induced residual stress is a relatively simple matter. Freshly formed ware is passed directly into a furnace (often called a lehr) at a temperature that will relax the residual stresses away in a matter of minutes.  For readers involved in fill-finish manufacturing, the equipment set-up for annealing looks similar to depyrogenation – just at much higher temperatures.  The annealed ware is then cooled down to room temperature at a sufficiently slow rate to avoid imparting any further substantial amount of residual stress.

So how do we verify that a pharmaceutical glass container has been properly annealed? Glass is considered an isotropic material in the absence of applied stress – i.e., the properties are the same when measured along different directions through the material. The presence of residual stress can lead to anisotropic effects with properties such as refractive index, a phenomenon also known as “photoelasticity”. In brief, light propagating through improperly annealed glass experiences two different refractive indices defined by the principal stresses within a local region of the glass. Recall that refractive index is a measure of the speed of light through a material relative to vacuum. In other words, light moving through a stressed glass is sub-divided into two components moving at different speeds – this effect is known as phase retardation or optical retardation. The optical retardation that is occurring within a stressed glass container will not be visible under natural lighting conditions. However, we can reveal the presence of the residual stress through a clever application of polarized light in a device known as a polariscope or strain viewer, as shown in Figure 2. The magnitude of optical retardation within a glass container (measured as the amount of retardation occurring per unit thickness of material) can be quantitatively determined through analysis of the colored fringe patterns that are observed when residual stress is present. ISO 8362-1 (Injection containers and accessories – Part 1: Injection vials made of glass tubing) stipulates that the maximum residual stress in a converted tubular vial should not produce an optical retardation exceeding 40 nm per millimeter of glass thickness (Footnote 4).

Up until this point, I have presented residual stress within glass as being a negative. However, this doesn’t always have to be the case. Residual stress can actually be used to improve the mechanical reliability of a glass object. The trick is to create a uniform, engineered profile in which the surface of the glass object is placed under a residual compressive stress; a balancing tensile stress develops within the interior. Compressive surface stresses in glass are typically achieved through thermal tempering (a process using controlled blasts of cooling air) or chemical strengthening (also known as ion exchange).

Questions or comments? – please leave them below or feel free to directly contact me.

Footnotes

1. PDA Technical Report 43 accessible at https://www.pda.org/bookstore/product-detail/7320-tr-43-molded-and-tubular-glass-containers.

2. You will find over time that I like to lean on examples from the worlds of cooking, food, beverages, etc. Making hard sugar-based candy is an easily accessible introduction to the process of making (organic) glass. For example, a mixture of table sugar (sucrose), corn syrup (glucose), and water is heated to the “hard-crack” stage (about 150°C). At this temperature, the sugars have been concentrated to a point that rapid cooling of the hot liquid will yield a brittle, glassy material that also happens to be edible.

3. I’m pretty sure that I have mentioned this before, but just in case – while a glass behaves much like a solid, it is by definition not a true solid phase. You’ll also note that I have two points, Tg and Tg’, marked on the V-T diagram. The point of intersection formed by extrapolation of the supercooled liquid and glass lines is sometimes used as another way of defining the glass transition temperature. This is problematic for reasons that are beyond the scope of this article – let’s just say it’s a reasonable estimate.

4. ISO 8362-1 accessible at https://www.iso.org/standard/74398.html