Abstract
Freeze-drying is commonly used to increase the shelf-life of pharmaceuticals and biopharmaceuticals. Freezing represents a crucial phase in the freeze-drying process, as it determines both cycle efficiency and product quality. For this reason, different strategies have been developed to allow for a better control of freezing, among them, the so-called vacuum-induced surface freezing (VISF), which makes it possible to trigger nucleation at the same time in all the vials being processed. We studied the effect of different vial types, characterized by the presence of hydrophilic (sulfate treatment) or hydrophobic (siliconization and TopLyo Si–O–C–H layer) inner coatings, on the application of VISF. We observed that hydrophobic coatings promoted boiling and blow-up phenomena, resulting in unacceptable aesthetic defects in the final product. In contrast, hydrophilic coatings increased the risk of fogging (i.e., the undesired creeping of the product upward along the inner vial surface). We also found that the addition of a surfactant (Tween 80) to the formulation suppressed boiling in hydrophobic-coated vials, but it enhanced the formation of bubbles. This undesired bubbling events induced by the surfactant could, however, be eliminated by a degassing step prior to the application of VISF. Overall, the combination of degasification and surfactant addition seems to be a promising strategy for the successful induction of nucleation by VISF in hydrophobic vials.
Highlights
Freeze-drying, or lyophilization, is widely used for the long-term storage of pharmaceuticals and biopharmaceuticals
We studied the effect of such coatings on the application of vacuum-induced surface freezing (VISF)
Pfirst and Plast were slightly lower in the presence of sucrose and, even more so, in mannitol
Summary
Freeze-drying, or lyophilization, is widely used for the long-term storage of pharmaceuticals and biopharmaceuticals. In a freeze-drying cycle, the product is first frozen, before ice is removed by sublimation during primary drying. This drying step is usually carried out at low temperature, avoiding harsh conditions for active ingredients. A further drying step, called secondary drying, is performed to allow for the desorption of residual moisture at a higher temperature, typically in the range 10–40 ◦ C. The size of the ice crystals formed during freezing corresponds to the porous structure obtained in the dried cake, provided that no shrinkage or collapse occurs. A larger porous structure promotes sublimation, reducing primary drying times [1], but penalizes desorption, making the secondary drying time longer [2]. The formation of ice has a dramatic impact on active molecules
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