Investigations on Polyplex Stability During the Freezing Step of Lyophilization Using Controlled Ice Nucleation—The Importance of Residence Time in the Low-Viscosity Fluid State

Lyophilization of a triply unsaturated phospholipid: Effects of trace metal contaminants

“…In addition, our results demonstrate that DLPC degradation occurred during the freezing step of lyophilization and was affected by sucrose concentration and buffer ionic strength in the freeze concentrate. Recent studies have shown that particulate formulations are especially susceptible to damage immediately after ice formation due to the high concentration of solutes and relatively high temperatures prior to complete solidification [58]. In contrast, we report that the high solute concentration actually serves to stabilize lipids against metal-catalyzed degradation, presumably by disrupting the association with metal contaminants.…”

Effects of Formulation and Process Factors on the Crystal Structure of Freeze-Dried Myo-Inositol

“…The lower concentration myo ‐inositol would remain amorphous during the high‐temperature period induced by the controlled nucleation method, leading to the freeze‐dried metastable crystal. Several controlled nucleation methods, including ultrasound, ice fog, quick pressure release of a chamber compressed with inert gas, and quick pressure release of a depressurized chamber are receiving increased attention due to their potential to shorten the ice‐subliming primary drying segment . Application of the controlled ice nucleation alters crystal form profiles of freeze‐dried mannitol .…”

“…Several controlled nucleation methods, including ultrasound, 48 ice fog, 49 quick pressure release of a chamber compressed with inert gas, 41 and quick pressure release of a depressurized chamber 38 are receiving increased attention due to their potential to shorten the ice-subliming primary drying segment. 50,51 Application of the controlled ice nucleation alters crystal form profiles of freeze-dried mannitol. 28 The depressurize/release procedure is applicable for most laboratory-scale lyophilizers, whereas other methods may allow better process control preferable for the production scale freeze-drying.…”

Stabilization of Plasmid DNA and Lipid-Based Therapeutics as Dehydrated Formulations

“…More recently, a research study based on a theoretical modeling had suggested that both the initial sample viscosity and the residence time of the particle in the low-viscosity fluid state are predominant factors in the retention of particle size during freezing. This model has been applied only to polyplexes (DNA complexed with a cationic polymer [105]), and further studies are needed to better understand the relevant mechanism of stabilization of other systems that are known to aggregate during freezing (e.g., liposomes, proteins). More than two decades ago, Crowe and collaborators proposed the so-called water replacement hypothesis to explain how sugars preserve the integrity of liposomes during drying [106,107].…”