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Freeze Drying - Articles and news items
Supplier news / 1 July 2016 / Biopharma Group
Quality by design (QbD) for lyophilisation is about building a robust process that proactively flags critical points and ensures consistent delivery of the best quality product, not only by minimising risk but also through greater understanding of the process itself…
Supplier news / 22 February 2016 / Biopharma Group
Blood transfusions have been used successfully since the early 1900s, and blood banks have been in use since 1914…
Supplier news / 19 February 2016 / Biopharma Group
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to make the recipient believe they are receiving something they are not in order to establish whether the true active agent has a noticeable remedy to the ailment it is intended to treat against the control…
Application Note: The sterility of the ControLyo™ process: reducing freeze dried product batch time without compromise to system integrity
Whitepapers / 18 January 2016 / Charles D. Dern P.E., Project Manager, SP Scientific
Controlled nucleation is the most significant new development in freeze drying in quite some time…
Freeze drying is gaining in importance as the number of biopharmaceuticals that are unstable in a solution increases. According to recent reports, a growth of 10% may be expected for freeze-dried products in the next 10 years. The technique offers the opportunity to gently dry temperature-sensitive drugs such as proteins or peptides. Since freeze drying is a rather expensive drying technology, formulation and process optimisation strongly focus on the design of a robust and fast cycle. Interestingly, partially crystalline systems offer advantages with regard to processability as well as product appearance…
In a pharmaceutical freeze drying process, it is mandatory to preserve product quality. This means that for a given formulation that has to be freeze dried, the temperature has to remain below a limit value corresponding to the eutectic temperature for a product that crystallises after freezing, with the goal of avoiding product melting, or to the collapse temperature for a product that remains amorphous at the end of the freezing stage, with the goal of avoiding dried cake collapse, as this could result in a product with unacceptable appearance, and it could cause some concerns during the drying process (e.g. lower sublimation flux and higher residual moisture). The denaturation of the active pharmaceutical ingredient is another issue that has to be accounted for when defining this limit temperature…
Issue 5 2012, Lyophilisation / 22 October 2012 / Henning Gieseler, Associate Professor at the Division of Pharmaceutics, University of Erlangen & CEO, GILYOS GmbH and Peter Stärtzel, Pharmaceutical Scientist, GILYOS GmbH
The stochastic nature of nucleation during the freezing step of the freeze-drying process has been regarded as a demerit in a process which is considered under rigorous control. The freezing performance of a product can impact its subsequent drying behaviour and the final product quality attributes. Hence, the idea to control this stochastic event and thus to directly influence the product morphology seems highly appealing. Sound understanding of the nature of nucleation and its link to drying performance, as well as the choice of a suitable technical concept, is of fundamental importance and the prerequisite to profit from the opportunities offered by controlled nucleation.
Freeze-drying is a commonly used method within the pharmaceutical industry. One of the key steps of the entire process is the initial freezing procedure. During freezing of an aqueous solution, the formation of ice does not start at the equilibrium freezing temperature, Tf (Figure 1, page 64). Instead, the solution shows supercooling below Tf until the first ice nuclei are formed at the nucleation temperature, Tn. Nucleation itself proceeds in a three-phase process. ‘Primary nucleation’ describes the point where initial crystal nuclei appear from molecular clusters exceeding a critical size1,2. The formed nuclei are further grown to ice crystals by secondary nucleation (also referred to as ‘crystallisation’) passing through the already nucleated volume1.
The underlying concept for the stabilisation of proteins during freeze drying is the formation of a glassy matrix in which the macromolecules remain isolated and immobilised. The concept relies on the so-called ‘vitrification hypothesis’ which assumes that the formation of an amorphous phase by lyoprotectants is mandatory to interact with the amorphous protein molecule. The use of lyoprotectants has also been found to be beneficial to preserve the original particle size distribution of nanoparticles during freeze drying. Until today, it has been speculated that the predominant mechanism to suppress physical instabilities of such colloidal particle systems is their embedment in a rigid glass. Today, there are various types of colloidal particles used in drug development, and sometimes the scientific literature gives evidence that glass formation was not necessarily required for stabilisation during freezing thawing or even freeze drying. The purpose of this article is therefore to briefly provide the latest insight into potential stabilisation mechanisms when freeze drying nanoparticles, a key knowledge for rational formulation and process design for such systems.
Pharmaceutical freeze-drying is used to stabilise delicate drugs which are typically unstable in solution over a longer shelf life. The liquid formulation is converted into a solid, highly porous cake which can be easily reconstituted prior to administration. The majority of freeze-dried products in the pharmaceutical industry are used for parenteral application. This route of administration demands high quality for both the drug product and the primary packaging material. Today, glass vials are routinely used for freeze-dried products as they provide some indispensable characteristics. Depending on glass composition, surface treatment, processing and geometry, a vast number of different glass vials are commercially available for customers. Selection of the optimum vial for a given product seems to become more and more difficult as manufacturers of moulded and tubing glass have refined their products over the last decades to fulfil market needs.
Process Analytical Technology (PAT) in Freeze Drying: Tunable Diode Laser Absorption Spectroscopy as an evolving tool for Cycle Monitoring
The most important critical product parameter during a freeze-drying process is the product temperature at the ice sublimation interface, Tp1. Once the product temperature in this area of interest exceeds the critical formulation temperature (typically denoted as “collapse temperature”, Tc) during primary drying, a stepwise loss of the cake structure may be observed2,3. This, in turn, can greatly impact the product quality attributes with regard to product appearance, reconstitution times, sub-visible particles and residual moisture content4.
The determination of structural changes of biopharmaceuticals during Freeze-Drying using Fourier Transform Infrared Spectroscopyb
Peptides and proteins are powerful active therapeutic ingredients used in a wide variety of serious conditions and illnesses such as diabetes, arthritis or cancer. The application of these so-called biopharmaceuticals has been rapidly increasing since the middle of the 1990s, facilitated by improvements in modern recombinant DNA technology and biotechnological manufacturing. The worldwide sales of the biotech drug market grew from 43 billion US$ in 2003 to over 75 billion US$ in 2007 according to a recent IMS Health market analysis. The major challenge in the development of stable protein formulations and dosage forms is to ensure their process and shelf life stability.
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