The relevance of shear, sedimentation and diffusion during spin freezing, as potential first step of a continuous freeze-drying process for unit doses

Publication date: 25 March 2018 Source:International Journal of Pharmaceutics, Volume 539, Issues 1–2 Author(s): Joris Lammens, Séverine Thérèse F.C. Mortier, Laurens De Meyer, Brecht Vanbillemont, Pieter-Jan Van Bockstal, Simon Van Herck, Jos Corver, Ingmar Nopens, Valérie Vanhoorne, Bruno G. De Geest, Thomas De Beer, Chris Vervaet Recently, a continuous freeze-drying process for the production of unit doses was presented and evaluated. In this concept, the freezing step is modified compared to traditional batch freeze-drying, as glass vials filled with a liquid formulation, are rotated around their longitudinal axis while cooled and frozen with a cold, sterile and inert gas (i.e. spin freezing). Finally, a thin frozen product layer spread over the entire vial wall is achieved. The aim of this paper is twofold: firstly, the relation between the rotation velocity and the relative difference between top and bottom of the frozen product layer thickness was determined for different vial types. Secondly, the impact of shear and centrifugal forces generated during spinning was examined, to find out whether they might cause pharmaceutical instability and sedimentation, respectively. Mechanistic and experimental evaluation showed that shear has no effect on proteins. Calculations showed that the sedimentation and diffusion velocity is too low to cause inhomogeneity in the product layer. In addition, Global Sensitivity Analysis (GSA) and Uncertainty Analysis (UA) ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research