Pharma Glass Compositions – Part 1. Glass network formers

Hello everyone – this post is a lightly edited version from a series that I initially started in 2023.? At the time, it was written mainly to check an item off my “to do” list. ?I had been referencing various pharmaceutical glass compositions in other articles, and so the idea was to build up a foundation to discuss the rationale behind pharma glass formulations.? Since that initial version, there have been some notable developments that further emphasize the importance of understanding pharma glass compositions.? For example, at the time this post is being written there are new revisions being proposed to the USP <660> compendial chapter concerning glass containers.? Among the various proposed revisions, a section has been included that provides much more definition around what constitutes a given glass composition – e.g., borosilicate glass, fused quartz glass, aluminosilicate glass, etc. ?I’m not intending to go into the proposed revisions any further here, but I strongly encourage you to review them if you are involved in the procurement, selection, qualification, or inspection of pharmaceutical glass packaging.

This will end up being a 6 part series in which we discuss the various categories of components used in pharma glasses (Parts 1 through 4), followed by a summary of modern formulations that are used in commercially available packaging, and ending with an overview of trace contaminants.? Let’s begin laying down a couple stipulations to restrict the scope of our discussion:

·?????? There are entire families of glass compositions in which an anion other than oxygen is a major component.? While technologically interesting, these materials are not used to produce glass containers.? We will only be focused on glasses in which oxygen is the majority anion component, otherwise known as “oxide glasses” (see Footnote 1).

·?????? An in-depth treatment of the principles of glass formation often presents two general schools of thought – a “structural” framework and a “kinetic” framework.? The kinetic framework essentially states that anything can be formed into a non-crystalline material provided that it is cooled at a sufficiently fast rate.? For example, it’s actually possible to make amorphous ice by rapidly quenching water (see Footnote 2).? While very interesting, it’s perhaps not as relevant to glass compositions used as primary packaging materials – this discussion is more firmly placed within the structural framework.? A key component of the structural framework is classifying glass-forming components within the context of conditions that are typically used to make glass at an industrial scale – i.e., cooling a molten liquid to a glassy state without appreciable forced cooling.

One of the original structural frameworks for glass formation places components into one of three major categories: network formers, network modifiers, and network intermediates (see Footnotes 3 and 4).? This a useful starting point, and we’ll be focusing on the network formers for today’s post.? However, this basic classification system ignores the intended function of components that are generally added to glass formulations in relatively small amounts.? In the case of glass for pharmaceutical packaging, these minor components include fining agents and (potentially) colorants.

One definition of a network former is a component that is capable of forming a glass on its own.? While multiple elements could be classified as network formers, only two are used in appreciable quantities in pharmaceutical glass – boron and silicon.? Both materials in an oxide form can be converted into a molten liquid that will yield a glass upon cooling without the inclusion of any other components.? Interestingly, one of these network formers (SiO? – otherwise known as fused quartz, fused silica, or vitreous silica in a glassy form) is highly useful from a technological standpoint, including as a potential option for parenteral packaging.? In contrast, glass formed purely from B?O? is extremely hygroscopic.? A freshly prepared sample of B?O? will quickly begin to form a hazy surface as it reacts with water vapor in the air – eventually it will completely convert to boric acid (H?BO?).

So what is this “network” that is being formed?? The network forming cations (Si?? or B3? in this case) are surrounded by a relatively small number of negatively charged oxygen anions for charge compensation – let’s say 3 to 5 (see Footnote 5).? This arrangement of a cation surrounded by a cage of oxygen anions is often described by polyhedra of various shapes (e.g., triangle, tetrahedron, octahedron, etc.) that can be linked together to form a three-dimensional network (see Figure 1).? We generally assume that these network forming polyhedra are joined together by a single shared oxygen, otherwise known as a bridging oxygen (BO – see Footnote 6).? Connecting SiO? tetrahedra together in a regularly repeating pattern gives rise to crystalline solids such as quartz.? However, the introduction of varying angles between adjacent polyhedra gives rise to long-range structural disorder that is a defining feature of glassy materials.

So far so good – but how do we actually build up the structure of a glass from these network formers?? It’s not as if we’re actually linking individual network polyhedra together one at a time like Lego? bricks.? Instead, we fuse raw materials together into a homogeneous molten liquid (see Footnote 7).? The atomic-scale structure of this molten liquid is quite similar to the glassy state – its what is “frozen in” during the cooling process.? Most everyone is familiar with the idea of using quartz sand (SiO?) as a raw material for glass making (see Figure 2).? Just like many of the raw materials used in glass making, sand is a naturally occurring mineral that is mined and processed in a way that provides a consistent chemical purity and particle size distribution.? Boron is? also frequently incorporated into pharmaceutical glass compositions using a naturally occurring raw material known as borax (chemical formula: Na?B?O?-10H?O).? However, unlike quartz sand, borax doesn’t just supply a network former to the glass composition.? It also introduces sodium, a glass making component that is also known as a network modifier (and the subject of the next post in this series).

Footnotes

1.?????? I’ve phrased this intentionally to include the possibility of other anion components (e.g., chlorine) being present in the glass formulation, albeit in relatively small amounts.? We will come back to this topic again in Part 4 of this series concerning fining agents.

2.?????? Cooling rates on the order of 10? K/s are needed to form what is called “low density amorphous ice”.? This can be accomplished by depositing water vapor on an ultra-cold surface or even spraying small droplets of liquid water into a sufficiently cold environment.? While a vast majority of ice on Earth is the crystalline form, it turns out that amorphous ice is the more common form in interstellar space.

3.?????? Reference: Zachariasen WH (1932).? The atomic arrangement in glass.? Journal of the American Chemical Society, 54: 381-3851.

4.?????? There is some variation in how this terminology is used in practice.? For example, “network former” might substituted with “glass former” and “network modifier” and “network intermediate” might be simplified to “modifier” and “intermediate”, respectively.

5.?????? There are generally 4 oxygen anions around a given silicon cation, an arrangement that is also known as 4-fold coordination or tetrahedral coordination.? Boron is a little more complicated.? Depending on the overall glass composition, boron can commonly adopt both 3-fold (trigonal) and 4-fold (tetrahedral) coordination states with oxygen.

6.?????? Once again, reality is a little more complicated.? For example, so-called “oxygen tri-clusters” are thought to form in some glass structures.?

7.?????? It’s perhaps a bit aspirational to say that “…we fuse raw materials together into a homogeneous molten liquid”.? In reality, compositional heterogeneities can occur, thereby leading to defects such as Stones and Knots.