Glass vials are the most common primary packaging material used in pharmaceutical freeze-drying. Depending on the manufacturing process, tubing or molded vials can be distinguished in the market. The practical relevance of each vial type depends on the fill volume of the product: small volume parenterals are typically freeze-dried in tubing vials while molded vials are primarily used for products with higher fill volumes.
The manufacturing process of tubing vials is a two-step process with glass tubes as an intermediary product. The manufacturing process for molded vials is also routinely performed in two steps: first, the molten glass is formed into an initial parison with a defined opening and a hollow inside. Second, this parison is transferred into a second mold where the final shape of the vial is formed by blowing the parison with compressed air. The formation of the initial parison in the first mold can either be performed by blowing the molten glass with compressed air (“blow-blow,” further abbreviated as BB) or pressing it with a metal plunger (“press-blow,” further abbreviated as PB). The PB process results in vials with a more uniform glass distribution and wall thickness. However, due to challenges with the plunger design for narrow-necked containers, it has historically been limited to more wide-necked containers. Recent advances in vial manufacturing have allowed manufacturers to produce smaller PB molded vials down to a size of 15-mL injection vials.
The thermal performance of a container system is of utmost importance to the freeze-drying process. Heat needs to be efficiently transferred between the heat transfer fluid inside the shelves and the product inside the container. During the freezing stage, heat from the freezing solution needs to be removed to adequately cool the product to its target freezing temperature. The sublimation process during drying requires energy to be transferred into the product. The heat transfer coefficient describes the rate of energy transfer per area, temperature differential, and time between the freeze-dryer and the container system. The coefficient for vial freeze-drying is referred to as the vial heat transfer coefficient Kv. Representative Kv values are essential for a quality by design (QbD) approach to develop or transfer freezedrying cycles: the calculation of the design space requires Kv as an input parameter. Knowledge of Kv values for different machines can be used for the adaptation of process parameters during scale-up or transfer of freeze-drying cycles to reduce the number of experiments required for successful transfer.
The influence of the PB manufacturing technique on molded vial Kv has not been evaluated so far. In the study attached, it is compared Kv of molded vials manufactured by the BB and PB techniques for the first time. Additionally, the influence of two different clear glass compositions and the effect of shelf load on Kv are studied. By comparing the Kv data with geometrical data of the investigated vial systems, a model for the calculation of heat transfer parameters based on geometrical data is proposed.
All vials were supplied by SGD S.A. Three different types of molded vials with a nominal fill volume of 20mL were used in the study: 20mL vials manufactured by a BB process (“20mL BB”), by a PB process with the same manufacturing mold as the BB vials (“20mL PB1”), and by a PB process with from a freezedrying perspective optimized geometrical features (“20mL PB2”). Two 50mL vials with different clear glass compositions manufactured by a PB process in the same molds (“50mL PB1” and “50mL PB2”) were analyzed. Additionally, 20mL serum tubing vials were analyzed (“20mL ST”) for comparison.
The sublimation experiments were performed on a LyoStar™ freeze-dryer from SP Scientific.
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