When Glass meets Pharma: Insights about glass as primary packaging material

By Dr. Bettine Boltres

Demands on a primary packaging material are not easy to meet these days. Increasingly, intense optical inspection, zero defect programs, and higher regulatory specifications require that drug packaging materials can no longer be taken for granted. Bringing us to the material "glass": What is glass anyway? How does it react with my drugs? Can I freeze it? Why is it breaking? Why is my drug being adsorbed to it? Why is this over 100-year-old borosilicate glass still the gold standard? If you have asked yourself these or other glass-related questions, this book is the right choice for you. It will guide you through the world of glass in a comprehensible and pharma-focused manner. Furthermore, this guide will keep you well-covered with the fundamentals on your first voyage into the world of glass.

Die Anforderungen an Primaerpackmaterialien sind heutzutage nicht leicht zu erfuellen. Intensive optische Pruefungen, Null-Fehler-Programme und strengere Behoerdenanforderungen haben dazu gefuehrt, dass Hersteller ein erhoehtes Augenmerk auf Packmittel fuer Medikamente richten muessen. Nehmen wir zum Beispiel den Werkstoff Glas: Was ist Glas ueberhaupt? Wie reagiert es mit meinen Arzneimitteln? Kann ich es einfrieren? Warum geht es kaputt? Warum lagert sich mein Medikament auf der Glasoberflaeche an? Warum ist Borosilikat-Glas, das es schon seit über 100 Jahren gibt, immer noch der Goldstandard? Wenn Sie sich diese oder andere Fragen rund um Glas schon einmal gestellt haben, ist dieses Buch das richtige fuer Sie. Es wird Sie umfassend und aus dem pharmazeutischen Blickwinkel durch die Welt des Glases fuehren. Gleichzeitig wird dieses Handbuch Sie auf Ihrer ersten Reise in die Welt des Glases sicher geleiten und Ihnen alle Grundbegriffe erlaeutern.

• Language: English
• Publisher: ECV Editio Cantor
• Release date: Aug 19, 2015
• ISBN: 9783871934339

Book preview

Contents

Preface

1. The nature of glass

1.1 Structure of glass

1.2 Chemical composition

1.3 Type I and Type III glass

1.4 Production of tubular and molded containers

2. Glass and heat

2.1 Viscosity

2.2 Stress

2.3 Coefficient of thermal expansion (CTE)

2.4 Thermal conductivity

2.5 Thermal shock resistance

2.6 Lyophilization

3. Glass and radiation and gases

3.1 Light transmission

3.2 Light protection

3.3 Gamma radiation

3.4 Permeability

4. Glass and liquids—chemical resistance

4.1 Reactions with acidic solutions

4.2 Reactions with basic solutions

4.3 Reactions with water

4.4 Testing methods for hydrolytic resistance

4.5 pH shift

4.6 Reactions with organic acids

4.7 Extractables and leachables

5. Glass surface reactions

5.1 Surface layer

5.2 Charge of the glass surface

5.3 Water contact angle

5.4 Weathering

5.5 Roughness

5.6 Sulfate surface treatment

5.7 Chemical toughening

5.8 Delamination

5.9 Protein adsorption

6. Glass strength

6.1 Ductile and brittle materials

6.2 Elasticity and plasticity

6.3 Stress and strain

6.4 Stiffness and modulus of elasticity

6.5 Hardness

6.6 Damage to glass

6.7 Crack growth

6.8 Breakage

References

Preface

Talking with pharmaceutical companies and giving technical seminars about glass for pharmaceutical packaging, I was faced by a huge curiosity for this material glass. Up to now, glass has always been taken for granted because it has been used for centuries. Therefore, it never really was in the spotlight of interest for pharmaceutical companies. However, with the increase in quality awareness, the development of new packaging materials, and the growing development of biopharmaceuticals, the possible interactions of the drug with the container have increasingly come into focus.

Several good books about glass chemistry, glass physics and its applications are available. On the other side, there are several good books on the market summarizing the various pharmaceutical packaging choices.

In order to close this gap, the book sets out to combine the world of inorganic glass chemistry with the world of organic drug molecules. Therefore, it focuses exclusively on pharmaceutical applications and endeavors to make the complicated chemical and physical fundamentals accessible to everyone, including non-scientists. This book was written especially for manufacturers, suppliers, and personnel working in regulatory affairs in the pharmaceutical industry but should also be of interest to all others who would like to dive into those parts of the glass world that are relevant for pharmaceutical applications. The topics covered in this book arose from the numerous fruitful discussions with staff of pharmaceutical companies over the past years.

Acknowledgements

Finally I would like to thank all colleagues and partners who contributed to this work, especially Volker Rupertus, Folker Steden, Michael Rössler, Daniel Haines and Florian Maurer.

Summer 2015 Dr. Bettine Boltres

1. The nature of glass

1.1 Structure of glass

Glass is one of the oldest materials in use. The art of working glass is known to be around 5000 years old. At that time, naturally occurring glass, e.g., obsidian, was already used for the production of hunting tools. Then the glass, due to its shiny appearance and because it can be stained so easily, was soon appreciated for valuable jewelry and decoration purposes. The oldest remaining glass recipe was found in the clay tablet library of the Assyrian king Assubanipal (700 BC) and reads approximately: ‘Take 60 parts sand, 180 parts ash from sea plants and 5 parts chalk—and you get glass.’ Up to modern times, this so-called soda-lime glass was used for packaging herbs, natural medicines, oils and other substances used for medicinal purposes. Around 200 BC, Syrian craftsmen invented the glassmaker pipe and melting ovens with which it was then possible to produce flat glass and hollow glass vessels. As widely spread as the use of glass is, it is hard to precisely describe it and find a definition that is internationally recognized and understood.

Fig. 1 Left: Structure of crystalline quartz. Right: Structure of amorphous quartz.

From the extensive scientific literature only a few attempts to describe the nature of glass can be mentioned here. One of the pioneers of glass research, Gustav Tammann (1861–1938), writes: In the glassy state substances are solid but not crystallized [1]. The American Society for Testing Materials (ASTM) stated in its compendium C162 in 1945 that glass [is] an inorganic product of fusion which has cooled to a rigid condition without crystallizing. This definition is still used in its most current version. In 1986, it was integrated into its German counterpart, the DIN 1259. The difference between the crystalline and the glassy state can be described by using its atomic structure. In figure 1, the structures of a quartz crystal and a quartz glass are shown. Quartz, which is found in nature as pure sand (SiO2 or silica) is built of SiO4 tetrahedra. In a crystal these are connected to form a six-sided prism as a member of the trigonal crystal system. It resembles perfect symmetry. Amorphous quartz (quartz in the glassy state) displays a more random chaotic arrangement.

Fig. 2 Solidification behavior of a crystal and amorphous material glass are shown in a temperature-volume diagram.

The transition from the crystalline structure to the amorphous structure takes place when the quartz is melted and rapidly cooled down to ambient temperature. The melting is done by introducing heat into the system. This energy is used to break the bonds between the atoms, whereupon they are able to move around freely in the system. At this point the glass melt is liquid. While it is cooled down, energy is removed (Figure 2), the atomic rearrangement (frequency of movement) becomes slower and the atoms try to position themselves in the pattern of an organized crystal. Only their very high viscosity (in the melting tank the viscosity is 10² dPas, which compares to honey) slows them down so that they freeze in