The first commercial database for Freeze-Dry Microscopy (FDM) to support your formulation and process development for freeze-dried products
LYOSCOPEDIATM is the first commercial database for Freeze-Dry Microscopy (FDM) which allows a user to quickly understand the freezing and drying behavior of a formulation as a basis for a subsequent freeze-drying process. The database was established by Dr. Henning Gieseler and his Freeze Drying Focus Group at the University of Erlangen (http://www.freeze-drying.eu). While the idea of having a comprehensive database for FDM information available from a single source was originally intended for basic University research, the collection of pictures and profound information became quickly requested by other organizations. Today, LYOSCOPEDIATM is a commercially available product which is continuously updated with latest Freeze-Dry Microscopy expert information.
Freeze-Dry Microscopy (FDM) is an established analytical procedure to study the freezing and crystallization behavior of a formulation during cooling. Moreover, the collapse or melting behavior during subsequent re-heating and drying of the same sample can be precisely delineated.1,2 FDM is an optical procedure. This means that the product behavior is observed visually in the freeze-drying stage as a function of a (controlled) temperature and (controlled) pressure.
LYOSCOPEDIATM is a database which contains various sample pictures of excipients and active pharmaceutical ingredients (API) commonly used for freeze-drying. Also, some examples of formulations are integrated into the collection. Pictures illustrate, among other things, ice nucleation3, an eutectic melt or the various stages of collapse behavior (e.g. onset of collapse, full collapse) of a given system, along with the corresponding product temperatures at the point of observation.
Why is it so important to study such product behavior?
Successful freeze-drying requires information of the tolerance of the product to temperature during the cycle. If the product temperature during the primary drying phase exceeds the (onset of) collapse temperature (Toc), structural changes in the inner product morphology are inevitable. This change of inner structure may result in negative target quality attributes of the freeze-dried product. First of all, shrinkage or even collapse might be observed when the product is amorphous (or melt-back when approaching the eutectic temperature, Teut, for a crystalline material) which greatly affects the elegance of the cake. Moreover, reconstitution times, residual moisture content or API stability might be compromised.1,2 Most interestingly, recent studies showed that many products can be freeze-dried in the so-called “microcollapse regime” (the product temperature range between onset of collapse and full collapse, Tfc).4 Such data provide another great opportunity to shorten a freeze-drying process.5
Why purchasing a license to use LYOSCOPEDIATM Examples of the benefit for formulation scientist and process engineers when applying LYOSCOPEDIATM may be summarized as follows:
Once a user receives such equipment, a technical training is typically provided by the vendor. However, right after that the most relevant questions come up which are NOT answered by sales people: How to prepare a sample for the measurement? What is an appropriate measurement methodology to determine the critical parameters for my formulation? How does “collapse” for my product actually look like? Again, note that FDM is a analytical procedure where the “result” is determined “visually”.
The database significantly shortens the time to get familiar with the FDM technology. Sample pictures of various substances illustrate the different “appearance” of collapse of a given system. Furthermore, technical notes help to identify the appropriate method for a given formulation. To avoid the obstacle of data interpretation, LYOSCOPEDIATM aids inexperienced users to precisely measure the “onset of collapse” of their formulation.
Advanced to Expert User:
Typically, collapse temperature data of many model systems are published in multiple literature references. Unfortunately, literature often uses different methodology to determine such data or, in some cases, does not even provide details on a method. Therefore, it is often a hassle to search multiple literature sources to obtain collapse temperature information required for daily work or for the simple citation in a manuscript. LYOSCOPEDIATM is a research based database which allows a quick and comprehensive access to such data. From experts, for experts.
Process Analytical Technology (PAT) and Quality by Design (QbD):
Are you using freeze-drying equipment with cycle optimization software? Does your freeze-dryer software require a definition of the “critical formulation temperature” for cycle optimization? LYOSCOPEDIATM provides access to such data, even when such analytical equipment is not available in your laboratory. Moreover, you might be able to compare existing Differential Scanning Calorimetry (DSC) data with FDM data to estimate the tolerance of your product to product temperature during the freeze-drying cycle.
Access to LYOSCOPEDIATM provides more than just pictures and temperature data! Once you have purchased a user license you will also find proprietary literature on Freeze-Dry Microscopy, application / technical notes regarding methodology and a special user forum to share FDM ideas or post questions related to FDM methodology and data interpretation.
The Freeze-Dry Microscopy data presented in LYOSCOPEDIATM were collected with the following equipment configuration:
Literature on Freeze-Dry Microscopy
Pikal MJ, Shah S 1990. The collapse temperature in freeze drying: Dependence on measurement methodology and rate of water removal from the glassy phase. International Journal of Pharmaceutics 62:165-186.
Meister E, Gieseler H 2008. Evaluation of the Critical Formulation Temperature in Freeze-Drying: A Comparison Between Collapse and Glass Transition Temperatures. European Pharmaceutical Review 13(5):73-79.
Meister E, Sasic S, Gieseler H. 2009. Freeze-Dry Microscopy: Impact of Nucleation Temperature and Excipient Concentration on Collapse Temperature Data. AAPS PharmSciTech 10(2):582-588.
Meister E, Gieseler H. 2009. Freeze-Dry Microscopy of Protein/Sugar Mixtures: Drying Behavior, Interpretation of Collapse Temperatures and a Comparison to Corresponding Glass Transition Data. Journal of Pharmaceutical Sciences 98(9):3072-3087.
|Johnson RE, Oldroyd ME, Ahmed SS, Gieseler H, Lewis LM 2010. Use of Manometric Temperature Measurements (MTM) to Characterize the Freeze-Drying Behavior of Amorphous Protein Formulations. Journal of Pharmaceutical Sciences 99(6):2863-2873.