Use of manometric temperature measurement (MTM) and SMART™ freeze dryer technology for development of an optimized freeze‐drying cycle

Finite Element Method (FEM) Modeling of Freeze-drying: Monitoring Pharmaceutical Product Robustness During Lyophilization

“…Lyostar II lyophilizer (FTS Systems, Stone Ridge, NY) equipped with SMART software can be operated in the SMART or Auto-MTM mode and the various input parameters that are needed for lyophilization experiments in these modes are described elsewhere [7]. Simplistically, SMART mode in our experiment setup was used to identify the initial process parameters for primary drying phase, and the process parameter optimization exercise was completed by execution of in the Auto-MTM mode.…”

“…At high T s , the water sublimates more quickly, and the solution dries faster. However, if the T s is too high and the product temperature rises above its collapse temperature (T c ), the product may have micro/macro collapse leading to a lower quality of the product [7]. The combination of T s and P c primarily defines the sublimation rate of water and plays a vital role in developing a good quality drug product.…”

“…With the SMART equipped Lyostar II freeze dryer, an optimized freeze-drying run may be developed with a few laboratory scale lyophilization experiments. The SMART/Auto MTM mode conducts a pressure rise test [7,[10][11][12][13][14] based on user inputs at predefined time. Using the pressure rise data, the software predicts an optimum shelf temperature and chamber pressure for primary drying phase of lyophilization.…”

“…Using the pressure rise data, the software predicts an optimum shelf temperature and chamber pressure for primary drying phase of lyophilization. In addition, critical product performance data, such as vial heat transfer coefficient (K v ) and mass transfer resistance (R p ) [7] are also outputs of the software. However, Tang [10,12] noticed that MTM measurement is no longer accurate after about 60% of total primary drying time especially for conditions like low shelf temperature, low chamber pressure and low dry layer resistance.…”

Preservation of Embryonic Stem Cells

“…For freeze-drying, it is crucial to keep the temperature below the so-called collapse temperature (T C ) (Abdul-Fattah et al 2007;Bellows and King 1972;Felix 2007;Fonseca et al 2004a;Fonseca et al 2004b;Gieseler et al 2005;Kramer et al 2009;MacKenzie 1966;Nail et al 2002;Pikal 1985;Pikal and Shah 1990;Pikal et al 1983;Rey and May 1999)) during primary drying (at the phase G). Otherwise, the sample may collapse during primary drying (Fig.…”