Scalable microfluidic method for tunable liposomal production by a design of experiment approach.

Liposomes constitute a widespread drug delivery platform, gaining more and more attention from the pharmaceutical industry and process development scientists. Their large-scale production as medicinal products for human use is all but trivial, especially when parenteral administration is required. In this study an off-the-shelf microfluidic system and a methodological approach are presented for the optimization, validation and scale-up of highly monodisperse liposomes manufacturing.

Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

In the present work, the effect of controlled nucleation on the stability of human growth hormone (hGH) during freeze-drying has been investigated. More specifically, the vacuum-induced surface freezing technique has been compared to conventional freezing, both with and without an annealing step. Size exclusion chromatography and cell-based potency assays have been used to characterize the formation of soluble aggregates and the biological activity of hGH, respectively.

Vacuum Induced Surface Freezing as an effective method for improved inter- and intra-vial product homogeneity.

The stochastic nature of nucleation makes it difficult to control batch homogeneity in conventional freezing, and this lack of control is in contrast with the current emphasis on Quality by Design. Among the techniques which have been developed to overcome this problem, Vacuum Induced Surface Freezing is probably the most promising for application in manufacturing, because it does not require additional equipment and can be scaled-up more easily than other proposed approaches. In this work, we summarize the impact of Vacuum Induced Surface Freezing on product morphology, and the efficiency of the subsequent drying steps as well.

Influence of controlled ice nucleation on the freeze-drying of pharmaceutical products: the secondary drying step.

Vacuum Induced Nucleation is often discussed in the context of primary drying performances and its tunability, with the potential to tailor the nucleation temperature to the desired porous structure. Instead, here we investigate its influence on secondary drying dynamics and, in particular, on rate of desorption and vial-to-vial inhomogeneity. So as to track the evolution of residual moisture during secondary drying, vials were regularly collected through a vacuum-tight sampling device; the residual moisture and the morphology of the porous cake was then determined by Karl Fischer titration and Scanning Electron Microscopy, respectively.

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

This paper aimed to study the impact of freezing on both within-batch (inter-vial) and within-product (intra-vial) heterogeneity. This analysis has been carried out using two freezing protocols, the conventional shelf-ramped method and the Vacuum Induced Surface Freezing, and placebo formulations containing both crystallizing (mannitol) and amorphous (lactose and sucrose) excipients. The freezing conditions (i.