Freeze-drying of enzymes in case of water-binding and non-water-binding substrates

Impact of vacuum-induced surface freezing on inter- and intra-vial heterogeneity

“…By contrast, the influence of Tm was minor, unless its value was so high to promote the melting back of the frozen solution. A further improvement 21 of both within-batch and within-product homogeneity could be obtained by the addition of the annealing treatment. It must be noted that all these results are not specific to the VISF method, but can likely be generalized to all those controlled freezing method proposed in literature where the freezing is induced by a perturbation on the top surface of the product.…”

“…The hemihydrate form was more recently reported by Yu et al and Nunes et al [19][20]. Not all these forms can effectively protect the active molecules against deactivation [21] and it has been found to have an impact on the stability of the product during its storage [22][23][24]. For example, the hemihydrate mannitol, if present in the lyophilized product, is not stable during storage, but is transformed into anhydrous crystalline mannitol (δ polymorph) by releasing its hydrate water within the amorphous phase, presumably containing the active pharmaceutical ingredient, increasing the rate of degradation.…”

Effect of Electron Beam Irradiation on Remaining Activity of Lyophilized Acid Phosphatase with Water-Binding and Non-Water–Binding Additives

“…These formulations were designed in order to obtain samples with different values of the fraction of water strongly confined within the dried product. [26] Furthermore, samples of the same formulation, but having different values of residual moisture, were produced by controlling the duration of the secondary drying stage. A batch of 100 vials (with 1 mL of solution per vial) were freeze-dried in lab-scale apparatus (Lyobeta 25, Telstar, Terrassa, Spain) equipped with miniature thermocouples (T type, Telstar, Terrassa, Spain), capacitance (Baratron 626 A type, MKS Instruments, Andover, MA, USA), and thermal conductivity gauges (Pirani PSG-101-S type, Infcon, Bad Ragaz, Switzerland).…”

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

“…α, β and δ) (Bauer et al, 2000;Berman et al, 1968;Botez et al, 2003;Burger et al, 2000;Kim et al, 1968) or as mannitol hemihydrate (Cavatur and Suryanarayanan, 1998;Cavatur et al, 2002;De Beer et al, 2007;Nunes et al, 2004;RomeroTorres et al, 2007;Yu et al, 1999). The polymorphic form of lyophilised mannitol was shown to have an effect in the stability of the lyophilised product during its storage (Cao et al, 2006;De Beer et al, 2009Pisano et al, 2013). For example, the presence of hemihydrate mannitol in a lyophilised product could increase the rate of degradation, because hemihydrate mannitol is transformed during storage into anhydrous crystalline δ-mannitol by releasing its hydrate water within the amorphous phase containing the active pharmaceutical ingredient (Ahlneck and Zografi, 1990;Nunes et al, 2004).…”

“…For example, the presence of hemihydrate mannitol in a lyophilised product could increase the rate of degradation, because hemihydrate mannitol is transformed during storage into anhydrous crystalline δ-mannitol by releasing its hydrate water within the amorphous phase containing the active pharmaceutical ingredient (Ahlneck and Zografi, 1990;Nunes et al, 2004). (Pisano et al, 2013) showed that a high content of mannitol in formulations containing mannitol and sucrose could better protect the enzyme molecules (acid phosphatase) from the dehydration stresses of lyophilization. Several studies showed the selection of the freezing method (Oddone et al, 2016) and the process conditions (Gan et al, 2004;Rene et al, 1993;Velardi and Barresi, 2008) as important parameters to be considered during cycle development.…”