Characterizing Vial Containers for Optimal Pharmaceutical Care

Thanks to the advancement in recombinant DNA technologies, the demand for biopharmaceuticals is rapidly growing. Nowadays, products like peptides, monoclonal antibodies, and vaccines occupy a large amount of the international market. However, since this type of drugs are extremely sensitive, different criteria must be taken into account during their development. Among these, the selection of the proper container is of primary importance. The chemical durability of the container is a crucial parameter when evaluating its pharmaceutical applications and it is fundamental to predict the interaction between the container and the drug. Some materials can interact with the drug and cause its degradation, affecting therapeutic outcomes and patient’s health. Because of its chemical and physical stability, glass is the material of choice to produce containers for pharmaceutical use, especially those suitable for parenteral solutions. Nonetheless, glass resistance is a complex phenomenon and depends on many factors: from the production of the container to the duration of its storage before use. During the manufacturing process, glass vials are subjected to multiple sources of stress that affect their propensity to corrosion. In fact, the temperature of the flames causes evaporation of the volatile species in the glass, generating heterogeneous zones that are more susceptible to the interaction with the future active ingredients. Other factors that can affect the quality of the container are washing or treatment done on the inner surface of the vial (e.g. sulfurization, siliconization). At the same time, the chemical durability of glass relies on the type of drug that is in contact with and on the processes performed by the pharmaceutical company upon manufacturing. Formulation is a crucial factor in selecting the most efficient container. In particular, its composition and pH range are key features that influence interaction phenomena with the inner surface. Additional treatments such as depyrogenation, sterilization, and storage condition (time and temperature) can also affect the corrosion propensity of glass. If not properly assessed, the previously mentioned factors can contribute to the progressive emergence of negative phenomena such as the detachment of glass lamellae from the container or the aggregation and adsorption of the drug. In this thesis work, the corrosion resistance of various containers for pharmaceutical use was evaluated under different stress conditions, through a chemical analysis and a morphological investigation. During the chemical analysis, glass elements were solubilized by different extraction methods which are representative of the main pharmaceutical products in the market. A morphological investigation was then carried out to assess the degradation of the glass inner surface after interaction with the solution. Protein stability within the various types of containers was also investigated using a model protein, Bovine Serum Albumin (BSA), with the aim of evaluating their glass-protein interaction. This was performed by studying protein stability by assessing the degree of aggregation using Dynamic Light Scattering (DLS) and the adsorption pattern using the colloidal gold staining test.

Thanks to the advancement in recombinant DNA technologies, the demand for biopharmaceuticals is rapidly growing. Nowadays, products like peptides, monoclonal antibodies, and vaccines occupy a large amount of the international market. However, since this type of drugs are extremely sensitive, different criteria must be taken into account during their development. Among these, the selection of the proper container is of primary importance. The chemical durability of the container is a crucial parameter when evaluating its pharmaceutical applications and it is fundamental to predict the interaction between the container and the drug. Some materials can interact with the drug and cause its degradation, affecting therapeutic outcomes and patient’s health. Because of its chemical and physical stability, glass is the material of choice to produce containers for pharmaceutical use, especially those suitable for parenteral solutions. Nonetheless, glass resistance is a complex phenomenon and depends on many factors: from the production of the container to the duration of its storage before use. During the manufacturing process, glass vials are subjected to multiple sources of stress that affect their propensity to corrosion. In fact, the temperature of the flames causes evaporation of the volatile species in the glass, generating heterogeneous zones that are more susceptible to the interaction with the future active ingredients. Other factors that can affect the quality of the container are washing or treatment done on the inner surface of the vial (e.g. sulfurization, siliconization). At the same time, the chemical durability of glass relies on the type of drug that is in contact with and on the processes performed by the pharmaceutical company upon manufacturing. Formulation is a crucial factor in selecting the most efficient container. In particular, its composition and pH range are key features that influence interaction phenomena with the inner surface. Additional treatments such as depyrogenation, sterilization, and storage condition (time and temperature) can also affect the corrosion propensity of glass. If not properly assessed, the previously mentioned factors can contribute to the progressive emergence of negative phenomena such as the detachment of glass lamellae from the container or the aggregation and adsorption of the drug. In this thesis work, the corrosion resistance of various containers for pharmaceutical use was evaluated under different stress conditions, through a chemical analysis and a morphological investigation. During the chemical analysis, glass elements were solubilized by different extraction methods which are representative of the main pharmaceutical products in the market. A morphological investigation was then carried out to assess the degradation of the glass inner surface after interaction with the solution. Protein stability within the various types of containers was also investigated using a model protein, Bovine Serum Albumin (BSA), with the aim of evaluating their glass-protein interaction. This was performed by studying protein stability by assessing the degree of aggregation using Dynamic Light Scattering (DLS) and the adsorption pattern using colloidal gold staining test.